RHEUMATOID ARTHRITIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Rheumatoid Arthritis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83606-X 1. Rheumatoid Arthritis-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on rheumatoid arthritis. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON RHEUMATOID ARTHRITIS ......................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Rheumatoid Arthritis.................................................................... 9 E-Journals: PubMed Central ..................................................................................................... 134 The National Library of Medicine: PubMed .............................................................................. 142 CHAPTER 2. NUTRITION AND RHEUMATOID ARTHRITIS ............................................................. 277 Overview.................................................................................................................................... 277 Finding Nutrition Studies on Rheumatoid Arthritis ................................................................ 277 Federal Resources on Nutrition ................................................................................................. 283 Additional Web Resources ......................................................................................................... 284 CHAPTER 3. ALTERNATIVE MEDICINE AND RHEUMATOID ARTHRITIS ....................................... 291 Overview.................................................................................................................................... 291 National Center for Complementary and Alternative Medicine................................................ 291 Additional Web Resources ......................................................................................................... 312 General References ..................................................................................................................... 325 CHAPTER 4. DISSERTATIONS ON RHEUMATOID ARTHRITIS ......................................................... 327 Overview.................................................................................................................................... 327 Dissertations on Rheumatoid Arthritis ..................................................................................... 327 Keeping Current ........................................................................................................................ 331 CHAPTER 5. CLINICAL TRIALS AND RHEUMATOID ARTHRITIS ................................................... 333 Overview.................................................................................................................................... 333 Recent Trials on Rheumatoid Arthritis ..................................................................................... 333 Keeping Current on Clinical Trials ........................................................................................... 355 CHAPTER 6. PATENTS ON RHEUMATOID ARTHRITIS.................................................................... 357 Overview.................................................................................................................................... 357 Patents on Rheumatoid Arthritis............................................................................................... 357 Patent Applications on Rheumatoid Arthritis ........................................................................... 407 Keeping Current ........................................................................................................................ 421 CHAPTER 7. BOOKS ON RHEUMATOID ARTHRITIS ....................................................................... 423 Overview.................................................................................................................................... 423 Book Summaries: Federal Agencies............................................................................................ 423 Book Summaries: Online Booksellers......................................................................................... 424 The National Library of Medicine Book Index ........................................................................... 433 Chapters on Rheumatoid Arthritis............................................................................................. 434 CHAPTER 8. MULTIMEDIA ON RHEUMATOID ARTHRITIS ............................................................ 437 Overview.................................................................................................................................... 437 Video Recordings ....................................................................................................................... 437 Bibliography: Multimedia on Rheumatoid Arthritis ................................................................. 439 CHAPTER 9. PERIODICALS AND NEWS ON RHEUMATOID ARTHRITIS ......................................... 441 Overview.................................................................................................................................... 441 News Services and Press Releases.............................................................................................. 441 Newsletters on Rheumatoid Arthritis........................................................................................ 446 Newsletter Articles .................................................................................................................... 446 Academic Periodicals covering Rheumatoid Arthritis ............................................................... 448 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 451 Overview.................................................................................................................................... 451 U.S. Pharmacopeia..................................................................................................................... 451 Commercial Databases ............................................................................................................... 453 Researching Orphan Drugs ....................................................................................................... 454
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APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 459 Overview.................................................................................................................................... 459 NIH Guidelines.......................................................................................................................... 459 NIH Databases........................................................................................................................... 461 Other Commercial Databases..................................................................................................... 465 APPENDIX B. PATIENT RESOURCES ............................................................................................... 467 Overview.................................................................................................................................... 467 Patient Guideline Sources.......................................................................................................... 467 Associations and Rheumatoid Arthritis..................................................................................... 476 Finding Associations.................................................................................................................. 481 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 483 Overview.................................................................................................................................... 483 Preparation................................................................................................................................. 483 Finding a Local Medical Library................................................................................................ 483 Medical Libraries in the U.S. and Canada ................................................................................. 483 ONLINE GLOSSARIES................................................................................................................ 489 Online Dictionary Directories ................................................................................................... 493 RHEUMATOID ARTHRITIS DICTIONARY.......................................................................... 495 INDEX .............................................................................................................................................. 603
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with rheumatoid arthritis is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about rheumatoid arthritis, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to rheumatoid arthritis, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on rheumatoid arthritis. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to rheumatoid arthritis, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on rheumatoid arthritis. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON RHEUMATOID ARTHRITIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on rheumatoid arthritis.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and rheumatoid arthritis, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Rheumatology Visit Frequency and Changes in Functional Disability and Pain in Patients With Rheumatoid Arthritis Source: Journal of Rheumatology. 24(1):35-42; 1997. Summary: This journal article for health professionals describes a study that examined the association between the number of visits to rheumatologists and changes in functional disability and pain over 6-month study periods among 127 patients who were treated by a rheumatologist at least once each year. The study also explored the association between the average annual frequency of visits to rheumatologists and both the progression of functional disability and average pain levels over periods of up to 10 years among these patients. Information on health care utilization and health status was obtained by biannual mailed Health Assessment Questionnaires (HAQ). Results indicate
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that the median visit frequency was 7.2 visits per year. The number of rheumatology visits was significantly associated with short-term changes in both functional disability and pain. Each additional visit in a 6-month study interval was associated with a decrease in the pain score in the current interval by an average of 0.02 points, and each additional visit was associated with a decrease in the HAQ Disability Index in the subsequent 6-month interval by an average of 0.0007 points. In analyses of long-term changes in health status, there was a U-shaped relationship between the frequency of rheumatology visits and the rate of progression of functional disability over time, with the lowest rates associated with average visit frequencies of between 7 and 11 visits per year. Average pain scores over time were positively correlated with the average annual frequency of rheumatology visits. Results demonstrate that short-term improvements in functional disability and pain were directly related to the number of visits patients made to rheumatologists. 21 references, 2 figures, and 3 tables. (AA-M). •
Importance of Enhancing Self-Efficacy in Rheumatoid Arthritis, The Source: Arthritis Care and Research. 10(1): 18-26. February 1997. Summary: This journal article presents health professionals with findings from a study that examined relationships among changes in self-efficacy and changes in other clinically relevant outcome measures among patients who had rheumatoid arthritis. The study population consisted of a subgroup of 44 participants from the stress management group of a prospective, randomized trial of a stress management intervention. Outcome measures included self-efficacy, depression, pain, health status, and disease activity. Correlational analyses reveal significant associations between changes in self-efficacy and changes in selected measures of depression, pain, health status, and disease activity. For example, as total self-efficacy increased, depressive symptoms decreased. At 15 months, higher self-efficacy was associated with lower pain on all four pain measures. At 3 months, improved functioning of the lower extremities was associated with enhanced self-efficacy. The speculation that health status changes may be related to changes in activity patterns is supported by data on walking speed. With higher selfefficacy, the time required for a 50-foot walk was reduced. However, improved walking speed may also have been associated with other observed changes, not just changes in disease activity per se. The observed associations were not due to changes in medication regimen or to nonadherence to the stress management program. The article concludes that the induced changes in self-efficacy following a stress management program were significantly related to other clinically important outcome measures. 5 tables and 34 references. (AA-M).
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Rheumatoid Arthritis: A Review and Suggested Dental Care Considerations Source: Journal of the American Dental Association. 130(5): 689-698. May 1999. Summary: This journal article provides dental health care workers with information from a study of the impact of rheumatoid arthritis (RA) and its treatment on the provision of oral health care. An extensive review of the medical literature in English on RA and dental care was undertaken. Although a MEDLINE search spanned the years from 1975 to the present, the most recent literature was prioritized. Appropriate medical and dental textbooks were also used. Nearly 200 articles and 7 textbooks were reviewed. Major features of RA, including its pathophysiology, diagnosis, clinical features, and treatment, were identified. The cause is unknown, but the etiology appears to be multifactorial and may involve infectious, genetic, endocrine, and immune participation. There is no specific laboratory test to diagnose RA. Although rheumatoid factors are found in more than two-thirds of adult patients with RA, they are not specific
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to it. The latest set of criteria for diagnosing RA was developed by studying patients who had already been diagnosed. The objective of RA therapies is to restore or maintain quality of life by relieving pain, reducing joint inflammation, and preventing joint destruction and deformity. Nonsteroidal anti-inflammatory drugs are the first-line treatment. Corticosteroids, another option, have both anti-inflammatory and immunosuppressive effects. Disease-modifying antirheumatic drugs, which have the potential to reduce disease activity or prevent joint damage, include gold, sulfasalazine, hydroxychloroquine, D-penicillamine, azathioprine, and leflunomide. Methotrexate has become a popular choice because of its immunosuppressive and anti-inflammatory effects. One of the latest and more novel approaches to treatment is cytokine therapy. However, long-term use of methotrexate and other antirheumatics can lead to various oral manifestations. The article discusses the clinical implications of RA in dental practice and provides guidelines on the dental management of people who have the disease. Considerations include the patient's ability to maintain adequate oral hygiene, xerostomia and its related complications, the patient's susceptibility to infections, impaired hemostasis, and untoward drug actions and interactions. 4 tables and 57 references. (AA-M). •
Rheumatoid Arthritis of the Cervical Spine Source: Journal of the American Academy of Orthopaedic Surgeons. 5(5): 240-248. September-October 1997. Summary: This journal article provides health professionals with an overview of rheumatoid arthritis of the cervical spine. Cervical involvement in patients who have rheumatoid arthritis occurs primarily in the upper cervical spine. The characteristic deformities are atlantoaxial subluxation, vertical settling, and subaxial subluxation. The typical patient complaints are neck pain and occipital pain. Subtle signs of myelopathy may also be present. Useful radiologic studies include plain radiography, tomography, and functional magnetic resonance imaging. The most helpful radiographic measurements are the anterior atlantodens interval, the posterior atlantodens interval, and assessment of vertical settling. Atlantoaxial subluxation greater than 9 millimeters (mm) with vertical settling and a posterior atlantodens interval less than 14 mm correlate with neurologic deficit. Nonoperative management does not change the natural history of cervical disease. Traditional surgical indications include intractable pain and neurologic deficit. The article discusses the more controversial indications for surgical intervention and proposes a rationale and protocol for treatment. The primary surgical objectives are to achieve stabilization of the affected segments and to relieve neural compression by reduction of subluxations or direct decompression. Arthrodesis provides reliable pain relief. Neurologic recovery occurs more consistently in patients with lower grades of preoperative myelopathy. 5 figures, 1 table, and 39 references. (AA-M).
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Arthritis 101: Juvenile Rheumatoid Arthritis Source: Arthritis Today. 14(1): 32-33. January-February 2000. Summary: This journal article uses a question and answer format to provide people who have children with juvenile rheumatoid arthritis (JRA) with information. There are three forms of childhood arthritis. Systemic onset JRA affects many bodily systems, including the joints, spleen, lymph nodes, liver, and heart. Polyarticular JRA affects more than four joints in a symmetrical manner. Joints most commonly affected are the knees, ankles, hips, feet, and small joints of the hands. This form of JRA has two subtypes. The first is characterized by the presence of rheumatoid factor and DR4 genetic type. The
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second is characterized only by joint involvement. Pauciarticular JRA usually affects four or fewer joints in an asymmetrical manner. The joints most commonly affected are the knees, elbows, wrist, and ankles. This form of JRA has three subtypes. In the first subtype, children have antinuclear antibodies and a high risk of iridocyclitis. In the second subtype, arthritis affects the spine and other joints, and children may test positive for the HLA-B27 gene. In the third subtype, joint involvement is the only feature. Although the cause of JRA is unknown, contributing factors likely include genetics and environmental factors. JRA can occur in boys or girls of any age, but it usually begins during the toddler or early adolescent years. Generally, it affects more girls than boys. Diagnosis of JRA is based on a medical history, physical examination, and possibly laboratory tests. Although in many ways JRA is treated the same as adult rheumatoid arthritis (RA), many drugs used to treat RA are not approved for children. Large doses of aspirin are usually used first, followed by disease modifying antirheumatic drugs if the disease progresses. 4 figures. •
Emerging Insights Into the Cause of Rheumatoid Arthritis Source: Journal of Musculoskeletal Medicine. 18(10): 459-461,464,469-472. October 2001. Summary: This journal article, the first in a special series of articles on the diagnosis and management of rheumatoid arthritis (RA), provides health professionals with information on the genetic and nongenetic factors that influence the onset, course, and severity of RA. This disease results from an abnormal immune response that occurs in a genetically susceptible host, leading to self sustaining, chronic inflammation that affects joints and, sometimes, organs. The strongest genetic components are polymorphisms of the major histocompatibility complex class (MHC) II genes. The MHC region contains several loci that encode for human leukocyte antigen (HLA). Allelic polymorphisms of HLA genes have been associated with several autoimmune diseases. Clinical studies suggest that HLA-DREB1 alleles modify the expression of established RA. Several environmental stimuli, possibly bacteria, viruses, or retroviruses, may contribute to RA in susceptible hosts. The immune system of persons with RA has features of premature aging, including reduced thymic function and T cell diversity. Oligoclonal T cell populations with natural killer features are common. A synovial cellular infiltrate is a consistent feature in RA. The inflamed synovium, or pannus, invades the joint and produces focal bone erosions. Cytokines, especially tumor necrosis factor alpha, are important mediators of inflammation in the rheumatoid joint. Although rheumatoid factors can exist in persons who do not have RA, the presence of rheumatoid factor foretells a more severe course of disease. 4 figures, 1 table, and 30 references. (AA-M).
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Part 1: The Role of Exercise: Rehabilitation Strategies for Patients With Rheumatoid Arthritis Source: Journal of Musculoskeletal Medicine. 17(4): 191-194,196-198, 203-204. April 2000. Summary: This journal article, the first of two parts and the ninth article in a special series on the diagnosis and management of rheumatoid arthritis (RA), provides health professionals with information on rehabilitation strategies. The article focuses on the general principles of rehabilitation as they apply to persons who have RA and the role of exercise in promoting optimal strength and function. For optimal preservation of joint function and range of motion (ROM), the patient who has RA should begin a rehabilitation program early. A history and physical examination focusing on musculoskeletal problems and functional evaluation are essential prerequisites. Progressive exercise is a key component of any rehabilitation program. The type, intensity, and duration of exercise depend on disease activity and stage. Patients begin
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with passive and active ROM movements, adding strengthening and aerobic exercise as tolerance and mobility permit. Primary strengthening exercises are isometric, isotonic, and isokinetic. Isometric exercise involves having the patient contract his or her muscle against a stationary object such as a belt, table, or machine that has a fixed arm. After muscles have been trained isometrically, the patient needs to incorporate isotonic exercises into the program. These involve moving the joint for several repetitions against resistance offered by free weights, elastic bands, or a machine. Isokinetic exercise is done with a machine and offers no strengthening advantage over isometric exercise. The best aerobic exercises for patients who have RA are stationary bicycling and swimming. Exercising at 70 percent maximum capacity for just 15 minutes 3 times a week usually produces improvement in 8 to 12 weeks. 3 figures, 9 tables, and 19 references. (AA-M). •
Rehabilitation Strategies for Patients With Rheumatoid Arthritis, Part 2: Modalities, Orthoses, and Assistive Devices Source: Journal of Musculoskeletal Medicine. 17(7): 385-387,391-393, 397-398. July 2000. Summary: This journal article, the second of two parts on rehabilitation strategies for patients with rheumatoid arthritis (RA), provides health professionals with information on the role of joint protective modalities, assistive devices, and orthoses that help patients exercise and function at their best. Modalities, orthoses, assistive devices, and education are important partners to exercise and medical therapy for patients with RA. Thermal modalities help decrease pain and muscle spasm in joints subacutely or chronically affected by RA; however, heat should be avoided during acute inflammation. Deep heat delivered via ultrasound or microwave is recommended for subacute and chronic capsular and tendon tightness that occurs in a large joint such as the shoulder or hip. Cold is recommended for decreasing pain, muscle spasm, and edema. Vehicles for delivering cold include ice packs, crushed ice, gel packs, and bags of frozen peas. Physical modalities that may increase comfort include massage, electrical stimulation, and, for patients with neck and back syndromes, traction. Orthoses help decrease inflammation, relieve pain, align and rest joints, and improve function, particularly in the hands, wrists, feet, and ankles. Orthoses can be static or dynamic. Assistive devices include large handled tools, sporting equipment, and kitchen utensils. Education improves compliance. Many patients resort to such alternatives as acupuncture or acupressure when conventional treatment brings no relief. Orthopedic referral is appropriate when joint realignment, stabilization, or reconstruction is necessary. 5 figures, 2 tables, and 10 references. (AA-M).
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Combination Therapy of Rheumatoid Arthritis Source: Journal of Musculoskeletal Medicine. 16(10): 583-589. October 1999. Summary: This journal article, the seventh in a special series on the diagnosis and management of rheumatoid arthritis, provides health professionals with information on the rationale for combination therapy with disease modifying antirheumatic drugs (DMARDs). These agents act slowly and suppress the chronic inflammation that leads to joint destruction in people who have rheumatoid arthritis. Combination therapy with multiple DMARDs theoretically offers the advantage of additive effects of drugs that act at different phases of the inflammatory process. At the same time, modification of one drug's metabolism by another's could reduce the potential for additive toxicities. Although early studies addressing the issue of simultaneous initiation of multiple DMARDs were discouraging or inconclusive, recent studies have more favorably demonstrated the enhanced efficacy of multiple DMARDs. Combinations that have shown promise in recent studies include methotrexate with sulfasalazine and
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hydroxychloroquine; methotrexate and cyclosporine; methotrexate, azathioprine, and hydroxychloroquine; and cyclosporine and intramuscular gold. Toxicities can be monitored according to American College of Rheumatology protocol. 1 figure, 4 tables, and 14 references. (AA-M). •
Emerging Therapies for Rheumatoid Arthritis Source: Rheumatic Disease Clinics of North America. 24(3): i-x, 465-662. August 1998. Summary: This journal provides health professionals with information on emerging therapies for rheumatoid arthritis (RA). The first article reviews the published data on the triple combination of methotrexate, sulfasalazine, and hydroxychloroquine to treat RA and compares the effectiveness of this triple combination with the combination of methotrexate and cyclosporin. An article on the use of cyclosporin in treating RA includes a discussion of its pharmacokinetics and efficacy, and guidelines for its use. Another article on the use of minocycline for the treatment of RA considers the scientific basis for the use of antibiotics in treating RA, the efficacy and toxicity of minocycline, and the place of tetracycline derivatives within the overall strategy of RA treatment. The next article reviews the expression, regulation, and activities of the cyclooxygenases; explains how nonsteroidal antiinflammatory drugs might interact with them, and comments on the new cyclooxygenase inhibitors that might be highly effective antiinflammatory agents without the gastrointestinal and renal side effects. Following are articles that present studies on oral tolerization as a treatment of rheumatoid arthritis; biologic agents and immunotherapy in RA; CD4 monoclonal antibody treatment of RA; soluble tumor necrosis factor receptor fusion protein as a therapy for rheumatoid arthritis; and antitumor necrosis factor-alpha monoclonal antibody therapy for RA. Other articles discuss interleukin (IL)-1 receptor antagonist and IL-10 as therapeutic agents in the treatment of RA, and T-cell receptor peptide vaccination in the treatment of RA. The final article focuses on the role of methotrexate in RA treatment and emerging therapies for RA. 17 figures, 19 tables, and numerous references.
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Arthroscopic Lavage Treatment in Rheumatoid Arthritis of the Knee Source: Journal of Rheumatology. 23(11):1872-1874. 1996. Summary: This study assessed the efficacy of outpatient arthroscopic lavage in rheumatoid arthritis (RA) of the knee. Researchers evaluated nine patients with RA and active synovitis of at least one knee. All patients were taking disease modifying antirheumatic drugs and nonsteroidal anti-inflammatory drugs and had failed intraarticular corticosteroid injection of the knee. Using the 1.9 mm office arthroscope and strict sterile technique, the affected knee was lavaged with at least 750 cc of normal saline. At the end of the procedure 40 mg triamcinolone acetonide was injected through the arthroscope. Assessment was done at baseline and 4, 8, and 12 weeks after the lavage using a visual analog scale for pain and 50 foot walk time. Results show that eight of the nine patients showed marked improvement in their pain and walk time. This effect was maintained at least 12 weeks after the procedure. The authors indicate that the procedure is simple and well tolerated, and may be an option when more conservative therapies have failed. 1 table, 1 figure, and 16 references.
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Validity of Self-Reported Diagnosis of Rheumatoid Arthritis: Results from a Population Survey Followed by Clinical Examinations Source: Journal of Rheumatology. 23(11):1866-1871. 1996.
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Summary: This study examined the validity of patient self-reported rheumatoid arthritis (RA); and assessed the predictive value of symptoms, health status measures, and demographic variables with respect to the actual diagnosis. Researchers used a postal survey in Oslo of 10,000 randomly selected individuals between 20 and 79 years old. Respondents reported musculoskeletal pain, stiffness, rheumatic diagnoses, disability, and mental distress. The patients reporting RA (either according to patient or doctor) were selected for further examination. Results show that of 5,886 respondents (3670 with musculoskeletal pain or stiffness) 158 patients (2.7 percent) reported having RA diagnosed by a doctor (n=107) and/or according to their own opinion (n=142). RA was confirmed by clinical examination in 35 of these 158 individuals (22 percent). Patients with perceived and actual RA differed regarding self-reported presence of swollen joints and disability score. Multivariate analyses failed to identify a set of useful predictors for the correct diagnosis. Researchers conclude that patient self-reported diagnosis of RA is unreliable for research or clinical purposes. 5 tables and 34 references. (AA-M).
Federally Funded Research on Rheumatoid Arthritis The U.S. Government supports a variety of research studies relating to rheumatoid arthritis. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to rheumatoid arthritis. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore rheumatoid arthritis. The following is typical of the type of information found when searching the CRISP database for rheumatoid arthritis: •
Project Title: 5 FLUOROURACIL (5 FU) PLUS LEUCOVORIN IN TREATMENT OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Bunch, Thomas W.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: The main objective of this study is to provide patients that have refractory rheumatoid arthritis with a better treatment option. Rheumatoid arthritis affects 1-2 percent of the population, and current treatments are inadequately efficacious for many patients. Immunosuppressive agents have been shown to clearly suppress the immunopathogenic mechanisms response for much of the disease activity. This is a clinical trial to determine the maximally tolerated dose of 5-FU and leucovorin when given on a daily x 5 schedule in patients with rheumatoid arthritis, to define toxicity
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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and to document any clinical benefit of this drug combination in patients with rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACTIVATION OF COLLAGENASE IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Windsor, L Jack. Oral Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2003 Summary: (Adapted from the applicant's abstract) - Rheumatoid arthritis is characterized by chronic inflammation and joint degeneration. This erosion of the joint is likely due to an imbalance of extracellular matrix synthesis and metabolism induced, in part, by members of the matrix metalloproteinase (MMP) family. The MMPs are zincdependent endopeptidases that are capable of degrading most of the components of the extracellular matrix. Active collagenase has been identified in the synovial fluid and in tissue extracts from patients with rheumatoid arthritis as well as in conditioned media from cytokine-stimulated synovial fibroblasts. It has been suggested that this activation of collagenase was initiated via the plasminogen cascade and/or involves stromelysin-1. However, the activation pathway of collagenase is a pivotal step in collagen degradation that still remains poorly understood. The overall aim of this study is to identify and characterize the mode of activation of fibroblast-type collagenase (collagenase-1) by synovial fibroblasts and manipulate its activation to determine if control of this process could be beneficial in the treatment of rheumatoid arthritis. The following specific aims are proposed to accomplish these goals: Specific aim 1 - Human synovial fibroblast cell lines capable of mediating destruction of a reconstituted matrix consisting of type I collagen fibrils will be identified and characterized. Collagen degradation initiated by these cells will be blocked by addition of inhibitory antibodies to collagenase-1 to demonstrate that this collagen degradation is collagenase -1 dependent. Intermediates in the activation of collagenase-1 will be identified and characterized by alpha2macroglobulin and TIMP (tissue inhibitor of metalloproteinases) capture techniques as well as by their reactivity in a fluorescent maleimide. In order to determine processing sites, amino-terminal sequencing will be carried out using activation intermediates purified by antibody affinity chromatography or by immunoprecipitation. Specific aim 2 - The investigators propose to distinguish the roles stromelysin and other MMPs play in the activation of collagenase-1 by synovial fibroblasts through addition of inhibitory antibodies made to each enzyme. Inhibitory antibodies to TIMP-1 may be included to provide an imbalance of enzymes to inhibitors which might lead to the activation of collagenase-1. Activation intermediates will be identified and characterized. Specific aim 3 - Once a synovial fibroblast cell line is identified that activates collagenase-1 independent of stromelysin-1 and other MMPs, it will be used to identify the mechanism(s) or factor(s) that are responsible for CL-1 activation. The feasibility of this specific aim is limited and depends on identifying a synovial fibroblast cell line that meets these criteria. The long-term goal of this project is to identify drugs or other reagents (antibodies) that can block the mechanism by which cells activate collagenase-1 and the other MMPs in order to prevent the continuous or intermittent destruction of the joints as seen in rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 11
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Project Title: ACUTE STRESS REACTIVITY AND DISEASE EXACERBATION IN RA Principal Investigator & Institution: Boyce, Thomas; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001 Summary: The objectives of this study are: (1) to conduct a laboratory investigation of 20 premenopausal women with RA in order to examine the effects of psychological stress on subjective, neuroendocrine, and immunologic responses that may be relevant to the pathogenesis of RA. For a subgroup of RA patients taking NSAIDs only, we will compare the magnitude of subjective and physiologic responses to a group of 20 healthy women who are diagnosed with carpal tunnel syndrome without RA, and matched for age, race, and NSAID use; (2) to determine if individual differences in the magnitude of physiologic stress responses can be demonstrated in patients with RA; (3) to conduct an exploratory and longitudinal investigation of whether such individual differences are associated with RA disease activity; (4) to carry out exploratory analyses examining potential associations between individual differences in physiologic reactivity and disease and psychosocial factors, including those that have been found to relate to distress and reported pain in RA samples. Examples include level of disease activity, social support, history of major negative events, and the personality traits of introversion and neuroticism, which have related to physiologic reactivity in healthy samples. The GCRC will be used as the site of the 3 hour laboratory investigation, which will be done during the follicular phase of each subject's menstrual cycle, and scheduled between 1-3 pm to control for circadian variations in hormone levels. The GCRC nurses will administer multiple questionnaires, perform frequent timed vital signs, coordinate two stress tasks and draw several timed blood samples during the stress producing tasks. The GCRC lab will perform the initial blood processing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADENO-ASSOCIATED VIRUS-MEDIATED SYNOVIAL GENE TRANSFER Principal Investigator & Institution: Hirsch, Raphael; Associate Professor of Pediatrics; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, PA 15213 Timing: Fiscal Year 2002; Project Start 10-SEP-1996; Project End 31-AUG-2007 Summary: (provided by applicant): Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are diseases for which current therapies are only partially effective and are associated with significant side effects. Gene therapy delivered locally to diseased synovium is a novel approach offering the potential to achieve steady-state levels of short-lived, specific biologic agents directly to diseased joints, thus minimizing possible toxicity associated with systemic delivery. Recombinant adeno-associated virus (rAAV) vectors have emerged as agents capable of delivering genes to tissues in vivo, including synovium, resulting in very long-term transgene expression. Importantly, a significant and growing number of reports show that rAAV vectors elicit minimal pathogenicity and immunogenicity. Preliminary data from our laboratory demonstrates that both proteasome inhibitors and certain adenovirus proteins dramatically improve rAAV mediated synovial gene transfer. We have also made the novel observation that proteasome inhibitors can regulate transgene expression in AAV-transduced synoviocytes. In this context, the current application will test the hypothesis that rAAVmediated, localized gene therapy can control human arthritis and will explore the
12 Rheumatoid Arthritis
mechanism of proteasome- and adenovirus-enhancement of rAAV-mediated synovial gene transfer. We will determine the specific site or step of transduction at which enhancement by proteasome inhibition and adenovirus helper proteins occur. Using a human RA/JRA-SCID model in which human arthritic synovium is implanted into SCID mice, we will deliver soluble TNF receptor (sTNFR), IL-4 and IL-10 by rAAVmediated gene transfer. The effects on synovitis and cartilage destruction of local, versus systemic, expression will be compared. To test the effects on synovitis of the removal of sTNFR, IL-4, and IL-10 following a period of expression, we will utilize a system for rAAV-mediated gene transfer under the control of a promoter that is active only in the presence of rapamycin. The potential of proteasome inhibitors to regulate transgene expression will also be determined. rAAV is the first vector with properties sufficiently attractive to be of potential clinical utility in arthritis. The proposed studies will provide a small animal model for testing the potential of rAAV-mediated gene transfer for human arthritides and may serve as the basis for the clinical application of rAAV to the treatment of these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AN L-SELECTIN LIGAND ANTIBODY FOR THERAPY OF ASTHMA Principal Investigator & Institution: Hemmerich, Stefan; Thios Biotechnology, Inc. 747 52Nd St Oakland, CA 94609 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 15-MAR-2003 Summary: (provided by applicant): Objective of this proposal is to develop a novel adhesion-blocking antibody for therapy of chronic inflammatory diseases like asthma and rheumatoid arthritis. Current treatments involve steroids or inhibition of inflammatory cytokines. An alternative approach is modulation of cell adhesion that is expected to limit inflammatory cell recruitment without immunosuppression inherent to anti-TNFalpha or steroid therapy. Leukocyte adhesion is mediated by the selectins. Lselectin binds to endothelial ligands defined by the monoclonal IgM MECA-79. MECA79 reactive vessels are found in peri-bronchial biopsies from asthmatics and in rheumatoid synovium. The MECA-79 epitope includes a functionally critical 6-Osulfation of N-acetylglucosamine contained within sialyl-Lewisx type capping groups of O-glycans on endothelial mucins. We have shown that MECA-79 treatment is therapeutic in asthmatic sheep. The MECA-79 epitope is therefore an attractive target for antibody-based anti-adhesive therapy. In specific aim 1 humanized single-chain antibodies specific to the MECA-79 epitope will be generated from phage display libraries. Aim 2 is to obtain a subset that blocks L-selectin binding. Aim 3 is to obtain a further set of antibodies that block lymphocyte adhesion and migration in-vitro and invivo. In phase II, resulting antibodies will be tested in disease-relevant animal models. Provided efficacy, a clinical lead will be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AN OUTCOME STUDY OF RHEUMATOID HAND ARTHROPLASTY Principal Investigator & Institution: Chung, Kevin C. Assistant Professor; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 08-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Rheumatoid arthritis (RA) affects 2.1 million Americans and costs the United States an estimated $8.7 billion annually in medical costs and wages. RA is a progressive disease, and approximately 25% of RA patients
Studies 13
experience hand deformities associated with the destruction of the metacarpophalangeal (MCP) joints. For the past 30 years, Swanson Metacarpophalangeal Joint Arthroplasty (SMPA) has been performed to correct MCP joint deformity in the rheumatoid hand. The goals of SMPA are pain relief, restoration of function, and aesthetic improvement. Despite its wide application, SMPA remains a controversial procedure. Hand surgeons and rheumatologists frequently disagree about the indications for this procedure and its value to their patients. In addition, most published studies to-date have been hampered by inadequate consideration of research design, small sample size, and inconsistent outcome measures. To provide a better understanding of the effectiveness of SMPA, a multi-center international outcomes study will be carried out to evaluate a cohort of RA patients with severe MCP joint subluxation who will either be enrolled into a SMPA (surgery plus medical therapy) group or a non-SMPA (medical therapy alone) group. Our research question asks whether RA patients who undergo SMPA will have different outcomes than those who are treated only medically. Patients will be evaluated at six months, one year, two years, and three years after surgery (SMPA group) or study entry (non-SMPA group). Outcome evaluations will be based on the Michigan Hand Outcomes Questionnaire, the Arthritis Impact Measurement Scales questionnaire, and standard objective hand function tests. The purpose of this project is to measure shortand long-term outcomes following SMPA and to define its indications for members of specific patient groups and disease severity strata. Most importantly, this project will combine the experiences of both surgery and rheumatology services to jointly evaluate this surgical procedure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALOG PEPTIDES IN COLLAGEN-INDUCED ARTHRITIS Principal Investigator & Institution: Myers, Linda K. Professor; Pediatrics; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 24-JUN-1995; Project End 28-FEB-2005 Summary: Collagen-induced arthritis (CIA) is an experimental model of autoimmune arthritis induced by immunization of susceptible strains of mice with type II collagen (CII). Our recent studies using HLA-DR transgenic (Tg) mice expressing HLA class II molecules associated with susceptibility to rheumatoid arthritis (RA) reveal that DR1 (DRB1*0101) and DR4 (DRB1*0401) can bind and present peptides derived from human (h) CII, and that mice bearing these transgenic DR molecules are susceptible to CIA. The immune response to hCII and arthritis can be down regulated by an analog peptide of CII, A12, CII 256-276 (F263->N, E266->D), when it is co-administered at the time of immunization with hCII. Human CII- sensitized spleen and lymph node cells from DR Tg mice produce increased amounts of IL-4 and IL-10 when cultured with Al2 in comparison to cells cultured with the wild-type CII peptide (CII 256-276). These observations suggest that the suppressive effect of A12 on immune response to CII and CIA in these DR Tg mice is mediated by a shift in the cytokine profile, from that of a Thl to a Th2. However, the mechanism(s) whereby the shift is brought about is not known. Al2 contains two amino acid substitutions as compared to the wild-type CII peptide. The substitutions are of two types, a) residue 263 that participates in peptide binding to the DR molecule, and b) residue 266 that interacts with the TCR. The hypothesis to be tested in this application is that the A12 effect on CIA is mediated through polarization of the specific immune response to a predominant Th2 profile, and that this polarization is caused by changes in the affinity between either DR and peptide or DR/peptide interaction with the TCR leading to altered T cell signaling and, consequently, the production of cytokines. We, therefore, plan to: 1) Identify the structural characteristics
14 Rheumatoid Arthritis
of the analog peptide Al2 that mediate its modulation of the immune response to CIIl and CIA in DR Tg mice; 2) Determine whether encoding the Al2 substitutions within the triple helical CII molecule increases the efficacy in inhibiting the autoimmune response in CIA; 3) Determine whether the suppression of CIA produced by A12 administration is dependent on IL-l0 or IL-4 secretion; and 4) Determine the mechanism by which Al2 alters T cell function by analyzing signaling pathways involved in T cell activation. Information gained from these studies will provide important insight for the design of novel therapeutic approaches that may prove beneficial in the treatment of autoimmune arthritis in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF GENETIC AND NONGENETIC RISK FACTORS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Criswell, Lindsey A.; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001 Summary: Rheumatoid arthritis (RA) is a chronic, disabling illness of unknown cause. Although both genetic and non-genetic factors are clearly important in disease onset and progression, little is known about specific risk factors. Furthermore, interactions among genetic and non-genetic factors are likely to be important, yet this remains an underexplored area of investigation. Substantial evidence implicates the Major Histocompatibility Complex (MHC) region in RA susceptibility. However, existing studies fail to define precisely which of the numerous candidate genes in this region influence disease risk, and whether they have independent or interactive effects. Specifically, strong evidence supports a role for the HLA-DRB1 "shared epitope," however, there is strong evidence that other MHC region loci likely influence RA risk or severity. Non-MHC genes must also be important, yet little is known about other genetic risk factors. Preliminary data by our group and others suggest a role for T cell receptor B (TCRB) genes in RA susceptibility. Finally, although non-genetic factors are estimated to explain at least 50% of RA risk, little is known about specific non-genetic risk factors. In this study, we will focus on two gene regions and two categories of nongenetic factors that are implicated in RA etiology based on pathophysiologic considerations and previous genetic and epidemiologic studies. Specifically, we will examine four candidates within or near the MHC region (HLA-DRB1, -DMA, tumor necrosis factor exposure to cigarette smoke. Our analysis will explicitly assess the presence of independent and interactive effects upon certain patient and disease characteristics. Our choice of analytic method, the transmission disequilibrium test, will allow us to study an ethnically diverse sample while maintaining false positive associations arising from population admixture. The results of this study will: 1) more precisely define the MHC contribution to RA; 2) evaluate the role of the TCRB gene complex; 3) provide new and important information about discrete non-genetic risk factors in RA onset and disease expression; and 5) provide important information about potential sources of genetic heterogeneity that will inform the design and analysis of future genetic epidemiologic studies of RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITIS
ANDROGEN
AS
ADJUNCT
THERAPY
IN
RHEUMATOID
Principal Investigator & Institution: Davis, John C. Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122
Studies 15
Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 30-JUN-2003 Summary: Rheumatoid arthritis (RA) is a chronic, debilitating multisystem disease affecting nearly two million persons in the United States alone. The incidence of RA in men under the age of forty-five is less than that reported in women, however the incidence approaches that of women in older age groups of men. This increased incidence in males coincides with decreasing levels of sex hormones. A hypogonadic condition characterized by low serum testosterone has been previously described in male RA patients compared with age-matched controls with osteoarthritis, ankylosing spondylitis and healthy controls. Patients with RA have significant disability with decreased function over time. Androgens have the potential to increase nitrogen retention, lean body mass, strength, and body weight which could slow the decline in function. Patients with RA also have both local and systemic forms of osteoporosis. There is evidence that androgens may stimulate the proliferation and differentiation of osteoblasts and osteoblast-like cells in vitro which may help reduce the rate of bone loss in RA. Previous studies in both animal models and humans seem to suggest that androgen administration may be beneficial in a number of autoimmune diseases including RA. In this study, we will examine the role of transdermal testosterone versus placebo in male patients with RA over a two-year period. Specifically, we will examine (1) the effect of testosterone on lean body mass and muscle strength with the use of whole body dual xray absorptiometry (DXA) scan and muscle strength testing, (2) the effect of testosterone on bone mineral density by DXA scan of the spine and hip, and (3) the effect of testosterone on disease specific measures of quality of life with validated instruments for quality of life. Additionally, measure of disease activity and side effects will also be assessed. The results of this study will (1) help to define the role of androgen administration and its effects on function through assessment of muscle mass and strength, (2) explore the potential benefits of testosterone therapy on bone mineral density in patients with both localized and systemic forms of osteoporosis, (3) define changes in quality of life in patients with RA treated with androgen, and (4) help to define the potential role of androgen therapy in other systemic illnesses where muscle wasting has a profound impact on quality of life (e.g. both inflammatory and noninflammatory muscle disease). In addition, this K-23 grant will provide opportunity for further career development through mentorship provided by an committee with multiple areas of expertise and formal education in the areas of clinical research design and conduct, outcome assessment development and analysis, and clinical trial analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOGENESIS & ALPHA V INTEGRINS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Storgard, Chris M.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 30-JUN-2004 Summary: Angiogenesis is central to the pathophysiology of rheumatoid arthritis (RA), and anti-angiogenic therapy targeting vascular integrin alphavbeta3, a crucial effector of the angiogenic process, may provide a novel approach to the treatment of this disease. The Specific Aims of this Mentored Clinical Scientist Development Award are [1] To characterize the dominant integrin pathway promoting angiogenesis in human RA, [2] To evaluate the effects of rational combination therapy targeting angiogenesis, cytokineinduced inflammation, and T cell mediated immunity, to determine the relative contribution of angiogenesis to the pathophysiology of RA, and provide pre-clinical evaluation of potential synergistic therapeutic effects, and [3] To examine the molecular
16 Rheumatoid Arthritis
mechanism of alpha V integrin-mediated endothelial cell survival during angiogenesis. The proposed research plan, in addition to providing valuable information, will equip the applicant with the necessary skills and techniques to investigate molecular mechanisms of cell function and signal transduction and perform anti-angiogenic gene delivery strategies as an independent investigator. Antagonists of alphavbeta3 are presently being evaluated in phase I/II cancer trials, and the results of this proposed study will provide the basis for alphavbeta3 antagonist therapy in future human arthritis trials. The strength of this career development award is based on the Mentor, Dr. David Cheresh, an international leader in angiogenesis research with a solid history of fostering the development of independent researchers. In addition, The Scripps Graduate Program in Macromolecular and Cellular Structure and Chemistry, in conjunction with The Scripps Research Institute and the Cheresh Laboratory, provide an outstanding training environment with exposure to state-of-the-art technology, permitting collaboration and intellectual exchange with many leading investigators. This comprehensive career development plan, in addition to the proposed research project will guarantee successful maturation of the applicant from physician to physician-scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTI TNF CHIMERIC MONOCLONAL ANTIBODY IN PATIENTS WITH RHEUMATOID ARTHRITIS Principal Investigator & Institution: Schilling, Margo L.; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001 Summary: This study is evaluating the efficacy and safety of chronic treatment with cA2, an anti-TNF chimeric monoclonal antibody, in combination with methotrexate in subjects with active rheumatoid arthritis despite treatment with methotrexate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITIS
ANTI-ANGIOGENIC
GENE
THERAPY
FOR
RHEUMATOID
Principal Investigator & Institution: Kasahara, Noriyuki; None; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-JUL-2002 Summary: The purpose of these studies is to evaluate the therapeutic potential of the angiogenesis inhibitors thrombospondin-1, angiostatin, and endostatin, for gene therapy of rheumatoid arthritis. Using lentiviral and helper-dependent adenoviral vectors as gene delivery systems for these angiogenesis inhibitors, we propose to develop an intraarticular treatment for rheumatoid arthritis. A considerable body of experimental and clinical data has documented that the pathogenetic process in rheumatoid arthritis involves the induction of a neovascular response. The process of new blood vessel formation, or angiogenesis, involves the interaction of substances that either stimulate or inhibit endothelial cell proliferation and migration. During pathologic processes such as rheumatoid arthritis, increased expression of angiogenic stimulators or decreased production of inhibitors alters the balance of positive and negative inputs of endothelial cell proliferation in favor of active neovascularization. We hypothesize that by increasing the concentration of these angiogenesis inhibitors in the synovial tissues during chronic inflammation, we may prevent the induction of new blood vessels and retard disease progression. The proposed experiments will allow us to: 1) optimize
Studies 17
delivery and expression of transgenes encoding the angiogenesis inhibitors thrombospondin-1, endostatin and angiostatin, following intra- articular administration of lentiviral and helper-dependent adenoviral vectors, 2) to determine the extent of systemic absorption and investigate the systemic effects of intra- articularly delivered anti-angiogenic lentiviral and adenoviral vectors, 3) to determine the in vivo chemopreventive effects of increased local expression of angiogenesis inhibitors on the establishment of arthritic disease, and 4) to determine the ability of lentiviral-and adenoviral-mediated delivery and local overexpression of anti-angiogenic genes to inhibit disease progression and angiogenesis in established arthritis. The development of an effective anti-angiogenic therapy for rheumatoid arthritis utilizing a relatively non-invasive intra- articular gene delivery strategy could have significant impact on patient quality of life, and potentially improve long-term outcome. In addition, by taking advantage of the ease of access by the intra-articular route, we anticipate that it will be possible to establish high local concentrations of potent angiogenic inhibitors while minimizing potentially adverse effects associated with systemic administration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIBODY STRUCTURE AND DYNAMICS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Kirschner, Karl N. None; University of Georgia 617 Boyd, Gsrc Athens, GA 306027411 Timing: Fiscal Year 2001; Project Start 01-JUL-2001 Summary: Rheumatoid factor (RF) proteins are present in the tissue of individuals who suffer from the autoimmune disease rheumatoid arthritis, which can be extremely painful and disabling. RF binds to specific epitopes in the IgG class of antibodies, forming an immune complex, which initiates an inflammatory response and eventually results in tissue damage of diseased joints. The profile of the glycans obtained from immunoglobulins (IgGs) collected from inflammatory diseased tissue can be significantly different from "normal" IgGs. Notably, RF binds to Fc only when the terminating galactosyl residues are no longer present, as seen in the Fc/IgG-RF/IgM crystal structure complex. This change in glycan sequence correlates with disease symptoms. The specific aim of this proposal is to gain a better understanding of the structure-activity relationship between human immunoglobulin G isotype 4 (IgG4) antibody and human IgM rheumatoid factor through the use of theoretical tools. This will be accomplished by achieving the following four goals: 1) Development of a suitable computational model for the IgG4 cleavage fragment (Fc), 2) Quantifying the extent of the Fc glycan mobility, 3) Determining the effect of degalactosylation on the Fc fragment structure and dynamics, and 4) Exploring the influence of point mutations in the Fc domain in close proximity to the glycan. The AMBER program suite will be used to perform minimization and dynamics on the Fc fragment. Due to the similarities between all antibody types this research may have implications beyond the specific Fc/IgG4-RF/IgM immune complex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIGEN AND NONANTIGEN DRIVEN TCR REPERTOIRES IN ARTHRITIS Principal Investigator & Institution: Winchester, Robert; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001
18 Rheumatoid Arthritis
Summary: One overall goal of this project is to delineate changes in putative antigen and non antigen driven T-cell clonal repertoire in psoriatic arthritis synovia before and after receiving potential disease modifying therapy in pilot trials. Once progress has been made towards this end parallel studies will be initiated in rheumatoid arthritis as the second overall goal. The first objective is to validate this approach of repertoire analysis to gain insight into the mechanism and efficacy of therapeutic interventions and for advancing insight into the cognitive immune recognition events driving the disorder. This project is based on the preliminary observation that the vast majority of synovial Tcells in untreated psoriatic arthritis consists of apparently non antigen driven single sequence clones, with the balance containing oligoclonally expanded, and putatively autoantigen- driven, clones of both CD4 and CD8 lineage. After methotrexate, the uninflammed synovium, in striking contrast, exhibited a profound decrease in this polyclonal component and a marked expansion of clones identical in sequence to those found as a minor feature in the active synovitis sample from the same joint. Accordingly, we hypothesize that methotrexate is an example of an agents that acts to reduce the non antigen-specific polyclonal recruitment that underlies clinical synovitis, but does not significantly affect clonal expansions of autoreactive T-cells involved in the fundamental immune recognition events driving the psoriatic arthritis. The proposed experiments exploit the potential to determine whether novel therapeutic agents affect either the putative antigen specific oligoclonal or the non antigen specific polyclonal component of synovitis, or both. The methotrexate studies will be continued along with pilot studies exploring treatment of an additional group of patients with a novel CD3 Mab that appears to anergize activated TH1 cells, the sTNFR:Fc competitive inhibitor Embrel and, potentially CD40L Mab. With the hypothesis that SDF-1 plays a significant role in the localization of a autoimmune response to the joint and its subsequent development into autoimmune disease, an envisioned future trial of a CXCR4 blocking agent is preliminary sketched as an example of a concept developed out of a fundamental gene discovery effect on the distinctive phenotype of cultured rheumatoid arthritis synoviocytes. In a second objective additional proposed studies are proposed to increase information on the nature of the surprising CD4 clonal expansions that are made more evident upon methotrexate administration and initiate an understanding of their role in psoriatic arthritis. It is hypothesized that they illustrate an instance of the "three cell interaction" involved in the generation of effector cytotoxic T lymphocytes under the influence of a cognate regulatory helper cell interacting with a dendritic cell. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIOXIDANTS AND FEMALE HORMONES IN THE ETIOLOGY OF RA Principal Investigator & Institution: Karlson, Elizabeth W. Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: The candidate is an Instructor in Medicine in the Department of Medicine, Division of Rheumatology, Immunology and Allergy at the Brigham and Women's Hospital and Harvard Medical School. Her research area is the epidemiology of rheumatic diseases, and the social and biological determinants of outcome in rheumatic diseases. Dr. Matthew Liang, Director, Multipurpose Arthritis and Musculoskeletal Diseases Center (MAMDC), Professor of Medicine at Harvard Medical School and Professor of Health Policy and Management at Harvard School of Public Health, will be her sponsor and co-mentor along with Drs. Frank Speizer, Charles Hennekens, Walter Willett and Meir Stampfer from the Channing Laboratory and Division of Preventive
Studies 19
Medicine. The research training program consists of the two studies described below, Research Seminars in the MAMDC, Channing Laboratory and Division of Preventive Medicine, courses at the Harvard School of Public Health, and close review by an Advisory Committee. The goal of the proposed studies is to define the role of dietary and hormonal risk factors in the development of rheumatoid arthritis (RA) in women. Specifically, it will test the potential protective role of antioxidants and N-3 fatty acids on the risk of RA, whether postmenopausal estrogen reduces risk and whether menopause increases risk of RA. The study utilizes information from two separate, complementary cohorts, the Nurses' Health Study, a prospective cohort of 121,700 women aged 30-55 years at baseline, followed since 1976, and the Women's Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals, aged 45 years and older. RA will be confirmed by a screening questionnaire regarding rheumatic symptoms and review of medical records. The study will identify potentially modifiable risk factors for primary prevention of RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTI-PROPERDIN MOAB AS A NOVEL THERAPEUTIC FOR ARTHRITIS Principal Investigator & Institution: Bansal, Rekha; Director; Novelmed Therapeutics, Inc. Bioenterprise, 11000 Cedar Rd Cleveland, OH 44106 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 14-MAR-2004 Summary: (provided by applicant): The complement system is an important host defense system, however, inappropriate and/or excessive activation of the complement system has been implicated as contributing to the pathogenesis of many disease states, including rheumatoid arthritis (RA). Rheumatoid arthritis (RA) is characterized by the occurrence of painful, swollen joints and none of the drugs currently administered to RA patients has been shown to cause regression of the disease. Therefore, there is a clinical need for potent new therapeutic agents for RA. There is evidence that the complement alternative pathway (AP) contributes significantly to the generation of proinflammatory agents in RA. Complement activation products such as C3a, C5a, and sMAC have been found within inflamed rheumatic joints and a positive correlation has been reported between the degree of complement activation and the severity of RA. Gliatech Inc. has identified a potent inhibitor of the AP, which consists of a blocking monoclonal antibody (GT6067) to properdin. Based on its ability to prevent AP activation in models of immune complex-mediated inflammation, there is reason to believe that such a MoAb holds great promise as an effective therapeutic agent for the treatment of RA. The focus of this study is to evaluate GT6067 in an antigen-induced model of arthritis in rabbits. This rabbit model possesses several key similarities with human rheumatoid arthritis and has been widely used in studies to identify novel RA therapeutic agents. Both Rekha Bansal, Ph.D. (P.I.) and James B. Parent are co-authors of the issued patent" Gupta-BansalR., Brunden, K. R. and Parent, J. B., A process of inhibiting complement activation via the alternative pathway. U.S. Patent 6,333,034B1, December, 2002 Key Words Complement; Monoclonal Antibodies; Properdin; Inflammation; Reverse Passive Arthus; Arthritis Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
20 Rheumatoid Arthritis
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Project Title: ARTHRITIS AND PHYSICAL TREATMENT Principal Investigator & Institution: Sun, Hui B. Anatomy and Cell Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, IN 462025167 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The long-term objectives of this proposal are to elucidate the effects of mechanical stimuli to tissue degradation of rheumatoid arthritis and to develop a physical treatment for relieving pain and stiffness of arthritic joints. Using two human synovial cell cultures isolated from rheumatoid arthritis patients, we have recently found that mechanical shearing at a few dyn/cm 2 transiently decreases the transcriptional levels of matrix metalloproteinase (MMP)-1, MMP-13 genes as well as ets-1 transcription factor, while the same shearing increases the mRNA levels of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2 and c-fos. These preliminary gene expression results suggest a potential use of mechanical shear stress as a therapeutic tool and allow us to test the following hypothesis: An appropriate nonstationary temporal profile of gentle mechanical shear stress at a few dyn/cm2 can maintain simultaneously a reduced mRNA level of MMP-1, 3, and -13 as well as an increased mRNA level of TIMP-1 and 2 through the down-regulation of ets-1 transcription factor. Two specific aims of this project are (i) to evaluate the proposed five non-stationary shear stress profiles for decreasing MMP rRNAs and increasing TIMP mRNAs, and (ii) to identify the function of ets-1 on mechanical stress-induced response in the simultaneous regulation of MMPs and TIMPs. We will isolate RNA from the stress-treated synovial cell cultures and determine the cDNAs levels of the specific MMPs and TIMPs as well as AP-1 and ets gene family members using a reverse transcription-polymerase chain reaction procedure. We will also measure the level of MMP proteins by immunoblotting and determine MMP activities by using zymography and a fibril degradation assay. By transfecting ets-1, we will test the function of ets-1 under mechanical stimuli. The proposed project will contribute to answer whether a non-invasive physical treatment can be developed for preventing from tissue degradation in arthritis joints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITOGENIC IGS--WHAT ARE THEY? WHY ARE THEY MADE? Principal Investigator & Institution: Mathis, Diane J. Professor of Medicine; Joslin Diabetes Center Boston, MA 02215 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: Rheumatoid arthritis is a common and debilitating autoimmune disease whose etiology and pathogenesis remain unknown. Small animal models of RA provide a means to dissect disease mechanisms. A mouse model that spontaneously develops a joint disorder with most of the characteristics of RA in humans was recently described. Disease in K/BxN mice is joint-specific, but is provoked by systemic T lymphocyte selfreactivity, resulting in pervasive T cell stimulation and broad B cell activation; both T and B cells are required. The critical role of B cells is to produce arthritogenic immunoglobulins: small amounts of serum from K/BxN mice can precipitate arthritis within days in healthy recipients, even those lacking lymphocytes; the serum activity resides in the IgG fraction and is neither rheumatoid factor nor anti-collagen antibodies. The two major goals of the experiments proposed here are to define the target(s) of the arthritogenic Igs generated in KBxN mice, and to determine what factors are responsible for their selective production, amongst the multitude of potentially autoreactive Igs.
Studies 21
More specifically, we propose to: (i) Identify the self-antigen(s) recognized by the arthritogenic Igs following three strategies - based on production of arthritis-promoting monoclonal antibodies, biochemical purification of tissue proteins, or screening of prokaryotic cDNA expression libraries. (ii) Elucidate the factors dictating selective secretion of the arthritogenic Igs, focussing on how the overwhelming T cell stimulation characteristic of this model, with its potential for universal non-cognate "help" for B cells, influences the fate and activity of B cells with various Ag specificities. Comparisons will be made between B cells that recognize self versus non-self Ags, and that see their Ags at different sites, in different forms or at different concentrations by crossing the KBxN strain with various already existing Ig or Ig/Ag transgenic or knockin lines. (iii) Determinate how tolerance of B cells expressing an arthritogenic specificity is maintained and broken by engineering the appropriate Ig gene knock-ins, and monitoring the behavior of their B cells in the normal context and in KBxN mice. We anticipate that these studies will provide important clues to the pathogenesis of arthritis in the K/BxN model and, hopefully, by extrapolation, in human patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATHEROCLEROSIS IN RHEUMATOID ARTHRITIS COHORT Principal Investigator & Institution: Del Rincon, Inmaculada; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 18-JUL-2001; Project End 30-JUN-2006 Summary: This K 23 Career Development Award will accomplish the double objective of training the candidate in patient-oriented research, and advancing current knowledge of the relationship between inflammation and atherosclerosis. For the career development component, the candidate will participate in the Master of Science in Clinical Investigation program, established at her institution with funding from a K30 Award from the NHLBI. This outstanding program is tailored to the candidate's needs, and will provide an in depth exposure to study design, data management and analysis, research ethics and scientific writing. The candidate will benefit from a rich environment of national experts in epidemiology, vascular imaging, cardiology, neurology, rheumatology and biostatistics. The objective of the research component is to examine to what extent atherosclerosis and cardiovascular morbidity are explained by systemic inflammation in rheumatoid arthritis (RA), accounting for the competing influence of established cardiovascular risk factors. The candidate will pursue three Specific Aims: (1) To determine the extent of atherosclerosis that is explained by cumulative systemic inflammation in RA; (2) To determine the role of inflammation in the progression of atherosclerosis in patients with RA; and (3) To determine the role of ongoing inflammatory disease activity as a risk factor for cardiac and cerebrovascular atherothrombotic events in RA. For Specific Aim 1, 680 members of an established cohort of RA patients will undergo two non-invasive procedures to measure atherosclerosis: high resolution B-mode ultrasound of the carotid intima- media thickness (IMT) and ankle-arm systolic blood pressure index. These measures will be compared to the severity of joint damage, which reflects cumulative inflammation in RA. For Specific Aim 2, the candidate will examine the influence of inflammation on the progression of carotid IMT over three years. For Specific Aim 3, the candidate will assess the influence of ongoing inflammatory disease activity on the incidence of cardiac and cerebrovascular events in the RA cohort. This research is a novel approach to understanding the contribution of inflammation to atherosclerosis, and will point the way for future research into the mechanisms of atherogenesis. In addition, it will have implications for the management of patients with RA and other inflammatory diseases,
22 Rheumatoid Arthritis
by extending the current indications for anti- inflammatory therapy to the prevention of atherosclerosis. This would ultimately lengthen life expectancy and improve the quality of life of people with inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATHEROSCLEROSIS IN RA Principal Investigator & Institution: Stein, Charles M. Associate Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Premature cardiovascular disease is a major cause of mortality in rheumatoid arthritis (RA). The mechanisms underlying accelerated atherosclerosis and its relationship to inflammation in RA are poorly understood. Recent studies indicate that inflammation through the effects of inflammatory cytokines, and oxidative stress, through lipid peroxidation, are important in the pathogenesis of atherosclerosis. We postulate that accelerated, inflammation-promoted atherosclerosis occurs in RA. Thus, we propose to test the hypotheses: 1) that structural and functional vascular damage is more frequent and more severe in patients with established RA than matched controls and is related to cumulative disease severity; 2) that this impairment of vascular integrity is associated with clinical and laboratory markers of inflammation, plasma homocysteine concentrations, and oxidative stress. To address these two hypotheses the relationship between longstanding inflammation and vascular integrity will be determined in a cross-sectional study of 75 patients with established RA in whom prospectively obtained clinical data are available for 15 years, and 75 matched non-RA controls. Endothelium-dependent, flow-mediated dilation of the brachial artery measured by ultrasound, and coronary calcium volume measured by electron beam computed tomography (EBCT) will provide functional and structural measures of vascular integrity, respectively. F2-isoprostane excretion, a reliable index of lipid peroxidation in vivo, homocysteine and lipid concentrations will be measured. Vascular integrity, oxidative stress, lipids and homocysteine will be compared in controls and RA patients. In the RA patients the relationship between RA activity and damage indices obtained over 15 years and vascular function and damage measures will be determined. Using the same techniques we will address hypothesis 3) that the rate of progression of vascular disease in patients with early RA can be altered by control of inflammation. In a prospective cohort of 100 patients with early RA receiving usual clinical care and 100 matched non-RA controls followed over 24 months the relationship between clinical and biochemical measures of inflammation and vascular integrity will be determined by comparing "responders" and "non-responders". These proposed studies will provide a basic understanding of the interrelationship between inflammation, lipids, oxidative stress and vascular damage, and will suggest strategies for reversing or preventing such damage in RA and, potentially, other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATIPRIMOD TO TREAT MULTIPLE MYELOMA AND BONE RESORPTION Principal Investigator & Institution: Jacob, Gary S.; Callisto Pharmaceuticals, Inc. 420 Lexington Ave, Ste 2500 New York, NY 10170 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): The goal of this proposal is to evaluate the potential of atiprimod, a drug previously explored for treating rheumatoid arthritis, to treat
Studies 23
human multiple myeloma (MM) and other metastatic osteolytic bone diseases. Atiprimod is an orally bioavailable drug that originally completed phase I/lla clinical trials in rheumatoid arthritis patients, with patient exposure of up to one year without serious side effects and no observable toxicity. Recent data on atiprimod's ability to induce apoptosis and inhibit proliferation of multiple myeloma cell lines and to inhibit osteoclast-mediated bone resorption, along with an increase in our understanding of the growth factors that drive multiple myeloma make atiprimod a unique therapeutic opportunity, as the drug simultaneously affects the multiple key growth factors of this disease along with the possibility of also inhibiting bone destruction, a major sequela of multiple myeloma. Atiprimod therefore also may be useful in treating primary and metastatic bone cancer as it provides a new mechanism to inhibit osteoclast-driven bone resorption, a major debilitating effect of these cancers. The specific aims of this Phase I proposal involve the use of cell culture experiments and appropriate animal models to evaluate atiprimod's ability to inhibit MM proliferation. We will evaluate the mechanism-of-action of this drug using techniques to determine how it inhibits cell growth, promotes apoptosis and inhibits secretion of VEGF. Using an in vitro model of adhesion of MM to BMSC cells that enables us to study juxtracrine and paracrine production and biological significance of IL-6, VEGF, stromal cell-derived growth factor 1, and IGF-1 in the BM milieu mediating growth, survival, drug resistance, and migration of MM cells, we will focus on how atiprimod exhibits its anti-MM activity. Atiprimod will also be evaluated in two animal models of human multiple myeloma at Dana-Farber Cancer Institute. Successful accomplishment of these studies will lead to a Phase II proposal to evaluate atiprimod in human multiple myeloma patients. Because atiprimod has already been in human safety clinical studies and there is a wealth of clinical and preclinical studies already available on the drug, we would expect to be able to expediously file an IND for atiprimod to treat MM patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTOIMMUNE ARTHRITIS: NEW DIRECTIONS Principal Investigator & Institution: Stuart, John M. Chief; Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): We propose to hold a scientific meeting entitled: "Autoimmune Arthritis: New Directions," on October 23 and 24, 2002 in Memphis, TN. The meeting will take place in the facilities of the University of Tennessee and will be jointly supported by the University, the NIH and Industry. Participants in the meeting will include internationally recognized experts on the subject of autoimmunity in the development of arthritis, both MD and PhD investigators will be included to provide cross-fertilization of basic science approaches to the understanding of clinically relevant problems. The primary focus will be on the animal model of Collagen-Induced Arthritis and its potential relationship to inflammatory arthritis in humans particularly Rheumatoid Arthritis. The animal model was discovered at the University of Tennessee 25 years ago. It provided the first proof that tissue specific autoimmunity could cause inflammatory arthritis. Since the discovery of CIA, this model has become widely used as a system for the study of inflammatory arthritis in general and of Rheumatoid Arthritis (RA) in particular. Although substantial progress has been made in understanding the pathogenesis of disease, recent discoveries including association with RA susceptibility genes, mapping of susceptibility loci, the confusing role of interferon gamma in disease pathogenesis, and the emergence on new therapeutic modalities have cast new light on disease pathogenesis and make this a topical subject. The objective of
24 Rheumatoid Arthritis
this meeting will be to disseminate information on the latest advances in understanding the development of autoimmune arthritis. The program will specifically address the following objectives: 1) Clarify the role of the major histocompatibility complex (MHC) in the pathogenesis of autoimmune arthritis 2) Establish how non-MHC genes contribute to both susceptibility and severity of disease 3) Determine the role of cytokines in regulating the expression of disease. 4) Investigate the ability of specific immunotherapy to prevent disease. Divergent views on these subjects have developed in different laboratories and in different parts of the world. This meeting will address those differences and provide a forum for developing new approaches and collaborations. Young Investigator travel awards are being provided to encourage involvement of trainees and other young investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION
AUTOIMMUNE
ARTHRITIS--GENETICS
AND
CELLULAR
Principal Investigator & Institution: Glant, Tibor T. Professor; Rush-Presbyterian-St Lukes Medical Ctr Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 29-FEB-2004 Summary: The overall theme of the Program project outlined in this application is the genetics, cytokine regulation and inflammatory cell migration into rheumatoid synovium of an autoimmune arthritis, induced by systemic immunization of mice with cartilage proteoglycan (aggrecan). This proteoglycan (aggrecan)-induced arthritis (PGIA) shows many similarities to human rheumatoid arthritis (RA) as indicated by clinical assessments such as radiographic analyses, scintigraphic bone scans and various functional tests, and by histopathologic studies of diarthrodial joints. The development, and then the progressivity, of this RA-like disease is based upon autoimmune reactions which develop against the mouse (self) cartilage proteoglycan. Arthritis develop only in genetically susceptible BALB/c mice or their F2 hybrids. It is accompanied with inflammatory cell migration into the joint, mediated by Th1 type cytokines. We combined three research projects in one program to utilize a very unique condition of accumulated information and experience of investigators. Project 1 will identify nonMHC-linked loci int he mouse genome which harbor genes responsible for proteoglycan arthritis, and then to identify these genes by positional cloning. Project 2 will evaluate the function and balance of Th1 and Th2 cytokines, manipulate the Th1 cytokine dominance in pre-arthritic stage of the disease and explore the mechanisms as how the anti-inflammatory cytokines suppress inflammation in synovium. In addition, this project will perform preventive studies in SCID mice using human synovium and antiinflammatory cytokines. Gene therapeutic approaches for delivery of Th2 cytokines in a site-specific fashion. Project 3 will study the function of CD44 in inflammatory cell migration and the different aspects of anti-CD44 treatment, and what the conditions of receptors of receptor shedding are in vitro and in vivo. This project will also utilize human synovium (normal or arthritic) in SCID mice to delineate how CD44 expression might be controlled by intracellular events (signal transduction). Each of the projects are highly integrated with each other and centered around a unique theme and supported by two Cores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AVONEX IN JUVENILE RHEUMATOID ARTHRITIS Principal Investigator & Institution: Sundel, Robert; Children's Hospital (Boston) Boston, MA 021155737
Studies 25
Timing: Fiscal Year 2001 Summary: This pilot study will evaluate the safety and efficacy of interferon B in the treatment of polyarticular juvenile rheumatoid arthritis (JRA), and to establish a dosing range for this medication in the treatment of polyarticular JRA. JRA is an incurable idiopathic condition that affects at least 70,000 children in the United States (Cassidy JT, Nelson AM, The frequency of juvenile arthritis. J Rheumatol 1988; 15:535). Polyarticular disease, which makes up at least 1/3 of this number, is one of the most severe subtypes owing to its tendency to cause pain and damage of multiple joints. A recent summary of outcomes in polyarticular JRA reported that 45% of children with this form of arthritis have active disease 10 years after onset of symptoms, and 54% have radiographic evidence of joint damage (Levinson JE, Wallace CA, J Rheumatol 1992; 19:6). Although new medications-especially methotrexate-appear to have improved the prognosis of children with polyarticular JRA, a uniformly safe and effective therapy is elusive. Interferon B is an ideal agent to test as a novel therapy for polyarticular JRA. Large scale use in patients of all ages with autoimmune disease has documented its safety, and it inhibits many of the processes thought to be central to the pathogenesis of joint inflammation in JRA (Cirell R, Tyring SK. Major therapeutic use of interferons. Clin Immunother 1995; 3:27-87). Subjects will receive each of two dosages by intramuscular injection once weekly of interferon B for 12 weeks each in a cross-over fashion. The order in which each patient receives each dose will be randomized, and both patient and physician will be blinded to the dose being administered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL TREATMENTS FOR RHEUMATOID ARTHRITIS Principal Investigator & Institution: Nicassio, Perry M. None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Behavioral interventions for rheumatoid arthritis (IRA) have had a salutary impact on patients' ability to manage difficult symptoms and other demands of this medical condition. Yet, the effects of behavioral treatments for RA on underlying disease activity and mood disturbance are largely undetermined. The proposed project compares cognitive-behavioral therapy (CBT), Tai Chi Chih (TCC), a form of movement-based meditation, and education control (EC) on measures of psychological adaptation (e.g., helplessness, coping), mood disturbance, sleep quality, pro-inflammatory cytokines, and RA disease severity. An important feature of the CBT intervention is that it incorporates strategies to enhance mood and diminish depressive symptoms. TCC has recently shown promise as an effective intervention in increasing physical activity and health functioning in older adults. Because of its emphasis on relaxation and exercise, TCC offers an interesting theoretical contrast to CBT. Two Ph.D. level psychologists will administer the CBT and EC interventions, while a highly experienced TCC instructor will administer the TCC protocol. A total of 210 IRA patients will be randomly assigned after a pre-treatment evaluation to one of the three interventions and will be assessed again at Week 8 of treatment, at post-treatment (Weeks 16-17), 8-month follow-up, and 1-year follow-up. A primary objective of the study will be to compare the clinical efficacy of CBT and TCC against EC. CBT and TCC are expected to contribute to significantly greater improvement in psychosocial functioning and IRA disease severity than EC. CBT, in turn, is hypothesized to lead to greater improvement than TCC on clinical endpoints because it teaches a variety of skills that patients can use to manage RA. This study will also explore the mechanisms through which CBT and TCC promote improvement in IRA disease severity. We
26 Rheumatoid Arthritis
anticipate, for example, that improvement in RA disease severity resulting from CBT and TCC will be mediated by reductions in pro-inflammatory cytokines (IL-1, TNF, IL6). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOMECHANICAL FACTORS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Guilak, Farshid; Associate Professor; Surgery; Duke University Durham, NC 27706 Timing: Fiscal Year 2003; Project Start 10-JUN-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Rheumatoid arthritis is a chronic arthropathy characterized by inflammation, proliferation and destruction of the articular cartilage. Although historically cartilage has been considered to be an "innocent bystander" of the disease, recent evidence suggests that the degradation of cartilage in arthritis involves an imbalance of the anabolic and catabolic activities of the articular chondrocytes, secondary to synovitis and joint inflammation. Chondrocyte metabolic activity is strongly influenced by soluble mediators (e.g., cytokines) and biophysical factors (e.g., mechanical stress). In particular, biomechanical factors may play an important role in the onset and progression of degenerative arthritis secondary to joint inflammation in rheumatoid arthritis. However, the sequence of biomechanical and biochemical processes regulating these events in vivo is still unclear. The primary hypothesis of this study is that, in rheumatoid arthritis, a loss of cartilage biomechanical function and the presence of inflammatory cytokines alters the metabolic response of chondrocytes to mechanical stress. Aim 1 of this project is to measure the mechanical properties of the cartilage extracellular and pericellular matrices in RA, and to incorporate this data in a theoretical model of the micromechanical environment of the cell. In Aim 2, we will determine the role of stress magnitude in the stimulation of nitric oxide and prostaglandin E2 production by chondrocytes, and determine the influence of these inflammatory mediators on matrix turnover. In Aim 3, we will determine whether mechanical stress has an additive or antagonistic effect on with certain inflammatory cytokines (interleukin 1, tumor necrosis factor alpha, and interleukin 17) in controlling the PGE2 synthesis and matrix metabolism. Currently, there is little information on the biomechanical changes in articular cartilage with RA. Understanding the biomechanical and molecular mechanisms of chondrocyte response to physiologic loading in an inflammatory environment may enable new therapies that are specific to the stage of the disease. As many pharmacologic therapies for RA are focusing on the NOS2 and COX2 pathways, investigation of the interaction of physical therapies with these pathways will hopefully lead to more safe and effective treatments for RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BMS 188667 & BMS 224818 INTRAVENOUS FOR RHEUMATOID ARTHRITIS Principal Investigator & Institution: Olsen, Nancy J. Professor; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001 Summary: Blockade of the second signal required for T cell activation in the immune response will alter the course of rheumatoid arthritis. The two agents to be tested bind to CD86 and CD80, which are signaling molecules on antigen presenting cells. SPECIFIC AIMS: This multi center trial will test the safety, preliminary clinical activity and immunogenicity of a new treatment for patients w/Rheumatoid Arthritis (RA). The
Studies 27
therapy that is being tested is multiple doses of BMS-188667 and BMS-224818. The major objectives of this study are to assess the preliminary efficacy of pharmacologic blockade of CD80 and CD86 w/these two drugs. The treatment is given via an intravenous infusion on study days 1, 15, 29 and 57. The patients will be followed for safety through study day 169. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARTHRITIS
BMS
188667/BMS
224818
INTRAVENOUS--
RHEUMATOID
Principal Investigator & Institution: Simon, Lee S.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN MECHANISMS OF RESILIENCE AND VULNERABILITY Principal Investigator & Institution: Davidson, Richard J. Vilas Professor; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002 Summary: (adapted from investigator?s abstract): This project builds on studies in Davidson?s laboratory that have highlighted the important role of prefrontal cortex and amygdala in the production and regulation of affective reactivity and affective style. This corpus of work has also focused on relations between differences in the central circuitry of emotion and peripheral measures of endocrine, autonomic and immune function. The first study in this project will examine the central and peripheral biology of resilience using subjects from two ongoing longitudinal samples that are being studied in Project 1. Subjects will be selected based upon their life history profile in conjunction with measures of psychological well-being as being either vulnerable or resilient. These individuals will then participate in two laboratory sessions. The first session will consist of a functional MRI (fMRI) session during which w hole brain echo planar images using BOLD contrast will be obtained in an event-related paradigm while subjects view positive, negative and neutral pictures. Structural images will also be obtained at this session for both anatomical localization of the functional data and for morphometric measurement of the hippocampus. The second session will consist of a psychophysiological assessment during which measures of brain electrical activity, impedance cardiography, startle and salivary cortisol will be obtained while subjects anticipate receiving reward or punishment, as well as during a mental stressor task. Vulnerable subjects are predicted to show more right frontal and amygdala activation, greater startle reactivity to threat and slower recovery following punishment, greater cortisol reactivity and increased sympathetic activation. The second study will examine patients with rheumatoid arthritis (RA) and fibromyalgia (FMS) along with matched controls who will be evaluated in Project 2. The study in this part of the project will provide an intensive biological assessment of the changes produced by a mindfulness meditation intervention. The assessment procedure used in Study I will also be used in this study. Subjects will undergo this two-session assessment before, just after, and 6 months following an 8-week mindfulness meditation intervention. The investigators predict that the mindfulness intervention will increase left anterior activation, decrease amygdala reactivity to negative stimuli, improve the recovery following punishment, increase pre-ejection period (PEP, i.e., decrease sympathetic activation) in response to
28 Rheumatoid Arthritis
mental stress and decrease cortisol compared with the initial assessment. Moreover, these biological changes are expected to predict improvements in clinical status among the patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAPRINE ARTHRITIS ENCEPHALITIS VIRUS INFECT: IMMUNITY, GENOME: GOAT AIDS MODEL Principal Investigator & Institution: Mdurvwa, Emmanuel G.; Tuskegee University Tuskegee Institute, AL 36088 Timing: Fiscal Year 2001 Summary: Caprine arthritis encephalitis virus (CAEV) belongs to the lentivirus subfamily of retroviruses. It integrates into the host cell genome and induces a persistent infection of domestic goats. CAEV infection causes encephalomyelitis in young goats, and mastitis, chronic progressive arthritis and synovitis in adult goats. The arthritis which results is similar in pathology to rheumatoid arthritis (RA) in humans. There is recent evidence that a novel CAEV variant occurs in humans and generates immune cross-reactivity to human immunodeficiency virus- I (IUV- 1). It is evident that CAEV is important not only as a pathogen in goats but as a vehicle for studying human diseases. We will use CAEV-induced disease 'in goats as a model to study the pathogenetic mechanisms of lentiviruses and also to investigate further some of the mechanisms that lead to arthritis. The obiective of this proposed project is to study molecular mechanisms of CAEV pathogenesis. This is important in the light of the possible use of CAEV-1ike lentivuiuses as -prophylactic agents against human viruses like EDIV-1. Specifically we propose to: i) investigate virus-host cell interactions by identifying and characterizing cell surface receptor(s) and defining the role of viral gp 13 5 and i do tha are essential for interaction with the cellular receptors; and ii) investigate some mechanisms that may be involved in the initiation and progression of arthritis by determining the role of various cytokines and chemokines, oxygen radicals, intracellular calcium fluctuations, circulating immune complexes, rheumatoid factor and also by identifying genes that are differentially transcribed during the infection. These results will provide a better understanding of a disease condition that is very similar to RA and in which the etiology is known. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIOVASCULAR DISEASE IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Morgan, Mary C. Assistant Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 27-JUL-2001; Project End 31-MAY-2006 Summary: (Taken from the applicants abstract): Rheumatoid Arthritis (RA) is a chronic, inflammatory autoimmune disorder that affects 1% of the U.S. population, with women of childbearing age preferentially stricken. There is a significant reduction in life expectancy in women with RA, which is due in part to premature cardiovascular disease. Acute myocardial infarction (MI) and congestive heart failure (CHF) are the leading causes of death in RA. The etiology of cardiovascular disease in RA likely involves an interaction between inflammation-induced and immune-mediated vascular injury, traditional risk factors, and hormonal factors. In RA, synovial inflammation is characterized by CD4+ T cell activation and pro-inflammatory cytokine excess, both within the joint and in the systemic circulation. The influence of such chronic immune system stimulation on atherogenesis and cardiovascular clinical events such as MI and
Studies 29
CHF is unknown. However, recent work has suggested that inflammation is responsible for atherosclerotic plaque disruption with vascular occlusion in non-RA patients. Increasing evidence implicates cellular and humoral components of the immune system in atherosclerotic plaque destabilization. Specifically, pro-inflammatory cytokines and CD4+ T cells have been identified in atherosclerotic lesions in association with plaque rupture and acute ischemic cardiac events, suggesting that they participate in plaque destabilization. This award will provide the opportunity for me, Mary Chester M. Wasko, MD, MSc, to obtain the specific skills necessary to develop into an independent clinical investigator. In this study I propose to: 1) determine the prevalence and predictors of vascular disease in women with RA; 2) compare the prevalence of vascular disease and associated risk factors in RA and systemic lupus erythematosus (SLE), an autoimmune disease also characterized by premature MI and CHF in young women; and 3) compare the prevalence of vascular disease in RA patients with and without a previous cardiovascular event. This study will provide valuable information for designing a future, prospective, multicenter study examining the value of B-mode ultrasound and EBCT in predicting incident cardiovascular events in patients with RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD44 IN RHEUMATOID SYNOVITIS Principal Investigator & Institution: Mikecz, Katalin; Rush-Presbyterian-St Lukes Medical Ctr Chicago, IL 60612 Timing: Fiscal Year 2001 Summary: This research proposal concerns the role of the hyaluronan (HA) receptor CD44 in synovial pathology during rheumatoid synovitis. We have demonstrated in mice with proteoglycan- and collagen-induced arthritis that a monoclonal anti-CD44 antibody eliminates joint swelling and inflammatory leukocyte infiltration. Our results suggest that CD44 participates in a variety of cell-cell and cell-matrix interactions at the site of inflammation. CD44- and HA-mediated events in inflammatory synovitis are current not understood. CD44 is present on synovial cells, and HA is a major constituent of synovial fluid and extracellular matrix in the normal joint. However, the amounts of CD44 and HA increase dramatically during inflammatory processes. Rheumatoid synovial cells and activated leukocytes express CD44 variant isoforms that are not detected in normal synovium. In contrast to normal joints, rheumatoid synovial tissue produces HA molecules that are poorly associated with matrix and diffuse into the extracellular space thus effecting joint swelling. Leukocytes, via the CD44-HA interaction, can be recruited and activated by HA present in the interstitial compartment of synovial tissue. Our preliminary results suggest that the production of IL-1 and TNFalpha by synovial cells is augmented by HA. Furthermore, CD44 and HA appear to be associated with the invasion of articular cartilage by rheumatoid pannus. In this study, we will compare synovial tissues and cells from normal and inflamed joints, in both murine and human systems, with respect to the molecular and functional properties of HA and CD44. We will delineate some of the regulatory and signaling mechanisms which may contribute to persistent leukocyte and synovial fibroblast activation. We also intend to determine if abnormal cell-matrix and cell-cell interactions in the rheumatoid synovium can be corrected by modulating CD44 function. The results of in vitro experiments will be conveyed to in vivo studies on a chimeric model of destructive synovitis, utilizing human rheumatoid synovium and cartilage engrafted into SCID mice. We believe that the findings of the studies proposed here will provide a better understanding of CD44- and HA-mediated events in arthritic processes, and open new avenues for therapeutic intervention in rheumatoid arthritis.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELLULAR INFLAMMATION
MECHANISMS
OF
ENDOGENOUS
ANTI-
Principal Investigator & Institution: Devchand, Pallavi R. Instructor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 30-NOV-2003 Summary: (Taken from the applicant=s abstract): About 1% of the US population (2.1 million people) have rheumatoid arthritis(RA). The most common RA is a late-onset disease, beginning at middle age with increased frequency in adulthood. While the exact causes for the different types of RA vary, the symptoms in each (swelling, redness, heat and pain) are reminiscent of the cardinal signs of inflammation. The social and financial impact of RA on both individual and nation are substantial, and due primarily to the debilitating symptoms of the disease (daily joint injury and inflammation). One approach to relieving the discomfort of this disease, is to treat the symptoms, i.e. an antiinflammatory treatment. Our knowledge of the cellular mechanisms involved in the resolution of acute inflammatory reactions that are neutrophil-driven is limited. Lipoxin A4 is a potent lipid-signaling molecule that mediates protective actions. This eicosanoid provides a model system for the evaluation of key targets in anti-inflammatory pathways. This research proposal is intended to test the hypothesis that in vivo, ALXR is a ligand-activated cell-surface receptor that tranduces the anti-inflammatory LXA4 signal, in part via a nuclear receptor pathway, to regulate the dynamics of an acute inflammatory reaction. A combined approach using transgenics, eicosanoid chemistry and molecular and cell biology techniques will be used to evaluate three main aspects of LXA. signaling in mature myeloid cells: 1.) To establish, in vivo, that the Lipoxin A4 receptor (ALXR) is a primary site of action for LXA4 and aspirin-triggered lipoxins. 2.) Identify nuclear events associated with LXA4 signaling and understand how these events counter-regulate pro-inflammatory transcription factors; and 3.) Use a woundhealing animal model to understand how ALXR modulates the dynamics of an acute inflammatory reaction towards resolution. The control of leukocytes is important not only for therapeutic use in disorders associated with uncontrolled inflammation (e.g., R A), but also has potential as a preventative measure against second organ injury during routine surgical procedures. Knowledge of endogenous anti-inflammatory lipid mediators and their sites of action could provide a platform for new therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOKINE RECEPTOR ANTAGONISTS IN INFLAMMATORY DISEASE Principal Investigator & Institution: Shahrara, Shiva; Medicine; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): There are many similarities in inflammatory responses observed in atherosclerosis and rheumatoid arthritis (RA). Chemokines and their receptors are important in both diseases. The long-term objectives of this application are to study the clinical and biological effects of C-C chemokine receptor 2 (CCR2) and CCR1/CCR5 antagonists in rodent arthritis. Furthermore we plan to determine the effect of key proinflammatory (TNF-alpha and IL-1beta) and Th1 promoting (IL-12 and IL-18) cytokines on CCR5 and CCR2 post-receptor signaling
Studies 31
events in the 2D61L-12 T cell line and endothelial cells in the presence of CCR5/CCR2 antagonists. Using CCR2/CCR5 antagonists in a model of inflammatory disease (RA) in vivo in addition to the knowledge acquired from studying the mechanism of proinflammatory cytokines effects on CCR2/CCR5 signaling pathways in vitro will help us understand and design more efficient in vivo studies in both RA and atherosclerosis. Several studies have used antagonists, binding proteins and antisense sequences to target proinflammatory cytokines, including TNF-alpha (antagonist; Etanercept), IL-18 (binding protein) and chemokine receptors CCR2/CCR5 (antagonists, antibodies and gene knockouts) in hope of mitigating the inflammatory reaction in atherosclerosis and RA. In order to investigate the effect of IL-12 and IL-18 on CCR5 and the effect of TNFalpha, IL-1beta and IL-8 on CCR2 downstream signaling pathways, we will immunoprecipitate CC chemokine receptors in cytokine treated cells and detect associated pathways by Western blot analysis. The purpose of using CCR antagonists is to validate that the cytokines exert their effect through these receptors. Additionally we will use CCR2/CCR5 antagonists in an in vivo inflammatory model of RA (rat adjuvant induced arthritis (AIA)) to examine their ability to decrease the severity and delay the onset of the disease. For this purpose we will determine the progression of indicators of inflammation, such as arthritis index, joint circumference, paw volume, joint count, arthritis severity, cell type recruitment and markers of bone destruction. Achieving these goals may give us valuable information in regard to molecular inflammatory mechanisms involved in atherosclerosis and RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHONDROPROTECTION TRITERPENOID
BY
A
NOVEL
RETINOID
AND
Principal Investigator & Institution: Vincenti, Matthew P. Research Assistant Professor; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: (Applicant's abstract): Rheumatoid arthritis (RA) and osteoarthritis (OA) are debilitating disorders that are characterized by progressive degradation of articular cartilage and bone. While the etiologies of these two diseases are quite different, the degradative components are similar in that the interstitial collagens of cartilage and bone are digested by a group of proteolytic enzymes that are collectively known as the matrix metalloproteinases (MMP). One MMP that has been recently implicated in the progression of RA and OA is collagenase-3, or MMP-13. Of the MMPs, MMP-13 is the most efficiently degrades type II collagen, the primary collagen present in articular cartilage. MMP- 13 is expressed in osteoarthritic cartilage and rheumatoid synovium, and is induced in chondrocytes that have been stimulated with the inflammatory cytokines interleukin-l (IL-I) and tumor necrosis factor-alpha (TNF). Thus, inhibition of MMP-13 in OA and RA is an important goal for therapies of chondroprotection. We have found that a novel retinoid, BMS-189453, inhibits MMP-13 synthesis in a mouse collagen-induced arthritis model. We have also demonstrated that a novel steroid, 2Cyano-3,12-dioxoolean-1,9-dien-28-oic Acid (CDDO), also inhibits MMP-13 synthesis in chondrocytes and has potent anti-inflammatory properties. In this application, we propose studies that will define, on the cellular level, the mechanisms of MMP-13 gene repression in chondrocytes by BMS-189453 and CDDO. Specifically, these studies will define transcription factors and signal transduction intermediates that are targets of these compounds. Since steroids and retinoids inhibit collagen degradation more effectively together, we will test the combination of BMS- 189453 and CDDO, to see if lower doses of each can be used. We will extend this work to establish the
32 Rheumatoid Arthritis
chondroprotective efficacy of BMS-189453 and CDDO, alone and in combination, in the STR/ORT spontaneous mouse model of OA, and in the mouse collagen-induced arthritis (CIA) model of RA. Our goals are to establish the potency of each compound in an inflammatory (CIA) and non-inflammatory (STR/ORT) model of arthritis, and assess the potential of combinatorial treatment, which may lead to therapies with fewer side effects. This work will examine cellular/molecular events and whole animal models to characterize the chondroprotective potential of a novel steroid and a novel retinoid for the treatment of arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLAIMS DATA PROJECT Principal Investigator & Institution: Kahn, Katherine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001 Summary: The purpose of this study is to evaluate the utility of claims data as a data source to evaluate quality of care in new onset rheumatoid arthritis; to measure the quality of care for patients with new onset rheumatoid arthritis with regard to arthritis co-morbid conditions and health care maintenance, and to identify factors associated with better attainment of quality standards. This study will prospectively follow a cohort of 400 patients with new onset rheumatoid arthritis for two years through patient surveys and claims data. Subjects will be enrolled through one large managed care organization (MCO) located in Southern California which represents an average of 2.8 million covered lives per year. Using a claims based algorithm, the 1998 through 1999 claims data for this MCO will be screened for incident cases of rheumatoid arthritis. Patients between ages 18 and 62 will be eligible for enrollment. A screening survey which will ascertain 1) whether a patient has been diagnosed with rheumatoid arthritis and/or 2) if the patient meets the 1987 American Rheumatism Association (ARA) criteria for rheumatoid arthritis by self report will be sent by mail to all eligible patients to invite participation. The first 400 responding patients who have had a prior diagnosis or meet the ARA criteria will be enrolled. Patients will complete telephone surveys which assess health status every six during the study. By using data elements from claims data, patient self report. and medical records, the structure, process, outcomes and quality of care will be assessed. Items measured in the claims data will be validated through the patient self report and medical record review. This study will inform us regarding the predictive value of claims data for identifying patients with rheumatoid arthritis and describing utilization. It will also describe the utility of claims data for assessing the process and quality of care for rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITIS
CLINICALLY
IMPORTANT
CHANGES
IN
RHEUMATOID
Principal Investigator & Institution: Ward, Michael M. Associate Professor; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-AUG-2002 Summary: Proper interpretation of the results of controlled clinical trials requires an assessment of not only the statistical significance of treatment differences but also of the clinical importance of such differences. Efforts to define criteria for important improvement in rheumatoid arthritis (RA) have thus far not considered the patient's perspective, even though patients' values represent the normative standard on which
Studies 33
improvements should be judged. The specific aims of this project are to determine if group criteria for important improvement in arthritis activity measures can be defined by assessing the agreement among patients of judgments of important changes in arthritis activity, and to determine if preference measures are useful measures of the importance of clinical changes. Because the importance of changes can be meaningfully judged only for measures that are sensitive to change, the sensitivity to change of arthritis activity measures will also be assessed. This observational case series study will measure changes in 12 arthritis activity measures, changes in patient preference measures, and judgments of the importance of changes in arthritis activity over one to four months in 240 patients with active RA. Consensus among patients regarding the magnitude of change in each measure considered important would allow group criteria for important improvement to be defined that were based on patients' valuations. Lack of consensus among patients, and therefore inability to define meaningful group criteria for important improvement, may indicate that clinical trials should include endpoints that more directly reflect patients' valuations of health, such as preference measures. This study will therefore also examine the reliability, construct validity, and sensitivity to change of patient preference measures, and will determine if preference measures better reflect changes judged to be important than do changes in traditional arthritis activity measures. This study will allow investigators to plan studies with knowledge of clinically important differences in arthritis activity measures, and will help clinicians and patients to understand better the relative benefits of different treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITIVE FIBROMYALGIA
FUNCTION
&
EXECUTIVE
CONTROL
IN
Principal Investigator & Institution: Glass, Jennifer M. Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Fibromyalgia (FM) is a disorder characterized by widespread musculoskeletal pain and the presence of tender points. Other symptoms, including fatigue, sleep disturbance and neuropsychological complaints contribute significantly to the morbidity associated with FM. One of the most prominent complaints in patients with FM is impaired cognitive ability. However, there is limited data on actual cognitive function in FM. Nonetheless, these cognitive complaints interfere with work and disrupt the lives of FM patients. The data available from our current work on cognitive function in FM and from other research, point toward a deficit in executive control of cognitive processes, especially working memory. Two experiments are proposed that will investigate various aspects of executive control and task-switching ability. The design includes standard neuropsychological tests as well as techniques developed in cognitive psychology. The latter techniques involve manipulation of experimental factors such as delay between encoding and recall that affect particular cognitive processes, such as decay from memory. This type of design allows a detailed view of the specific cognitive processing mechanisms that are affected in FM. Because FM is associated with other symptoms that could impact cognitive function, two special control groups are included in the design in addition to healthy controls. A group of rheumatoid arthritis patients will provide a control for the attentional demands of managing chronic pain. A group of depressed patients will provide a control for depression in FM, since patients with FM frequently report more depressive symptoms than healthy controls. We hypothesize that FM is associated with cognitive dysfunction that cannot be explained solely on the basis of pain or depression.
34 Rheumatoid Arthritis
This research will lead to a better understanding of the characterization of cognitive dysfunction in FM, as well as the potential causes of this dysfunction. The emphasis on executive control processes is important because these are critical in many demanding work and life situations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPUTERIZED RHEUMATOLOGY
PATIENT
SELF-ASSESSMENT
FOR
Principal Investigator & Institution: Soll, Andrew H.; Cpm Systems, Inc. 1665 Michael Ln Los Angeles, CA 90272 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Proposed work develops content and tests the feasibility of CarePrep, a Web-based patient self-assessment instrument, in patients with rheumatoid arthritis (RA). RA is a common disorder that usually causes rapid loss of function, but early, aggressive treatment improves outcomes. Instruments that measure health-related quality of life (HRQL) are useful to assess treatment in RA populations, and probably are useful in monitoring and adapting therapy in individual patients. Whereas paper HRQL instruments are difficult to use, Web-based instruments provide an attractive approach. The CarePrep interview has already been built for general medical and gastroenterological assessment. CarePrep uses a modular design wherein every element can be configured. Configuration profiles can be crafted for a variety of clinical or research tasks; profiles are selected at appointment time. Aims: 1) The wellestablished instruments for HRQL, the arthritis-specific Health Assessment Questionnaire (HAQ) and the generic RAND-36 (or Short Form 36) will installed into CarePrep. A streamlined HRQL tool (CPQL) with screening questions and configured branching will also be developed. The existing CarePrep review of systems (ROS) will be adapted to characterize symptoms, identifying extraarticular sites of disease activity and detecting potential drug toxicity. A graphic will gather patient-derived tender joint counts, a reliable index of disease activity. A modified Delphi process will be used to structure critique by experts. The CarePrep output is prioritized, problem-oriented report designed for efficient physician review; scores for joint counts and HRQL domains will be included. 2) The application will be pilot tested and focus groups held. 3) Testing 100 RA patients, accuracy of the ROS will be assessed by physician rating of CarePrep reports. The sensitivity of screening CPQL questions will be assessed by bypassing branching thresholds so that all HRQL questions will be asked. The patient's CarePrep joint count will be compared to a physician count. 4) Feasibility testing will be conducted that mimics anticipated use of CarePrep in practice settings. Patients will do the computer interview and then evaluate the experience. Practicing physicians will review the report, evaluate the patient, and then assess the utility of the report. We anticipate that CarePrep will be well accepted by patients and physicians and provide efficient monitoring of RA Status, thereby allowing more cost-effective care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPUTERIZED RHEUMATOID HANDS
RADIOGRAPHIC
OUTCOMES
FOR
Principal Investigator & Institution: Duryea, Jeffrey W.; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2005
Studies 35
Summary: (provided by applicant): Rheumatoid arthritis (RA) is a very painful condition with tremendous societal impact. Nearly one percent of the population suffers from RA and the annual cost to the North American healthcare system from arthritis in general has been estimated at $64 billion. Symptoms range from mild discomfort and pain to loss of joint function as the disease progresses to its end-stage. This enormous healthcare problem is best met by the prescription and development of effective therapies. In order to evaluate these therapies, highly accurate and reproducible methods are required to quantify the state of the disease. Radiographic evaluation of hand films is currently used to assess disease progression though the use of semiquantitative subjective scoring systems. These methods, however, are subjective and suffer from significant reader variation. In addition, the need for specialized training makes the systems costly and difficult to implement on a widespread basis. There is currently no truly quantitative method to assess arthritis progression in the affected joints. To address this need we propose to apply sophisticated image processing, multivariate analysis, neural networks, and regression tree methods to hand radiography. We will perform a quantitative and systematic study of radiographically visible structural changes due to RA. This work will provide previously unavailable objective and disease sensitive radiographic outcome measures of RA progression. The result will be a computer-based system with improved disease sensitivity, which will lead to more accurate evaluation and appropriate prescription of therapies. This work will play a major role towards alleviating the effects of this debilitating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROLLED FIBROMYALGIA
FAMILY
STUDY
IN
PATIENTS
WITH
Principal Investigator & Institution: Arnold, Lesley M. Associate Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, OH 45221 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: Fibromyalgia, a chronic musculoskeletal pain disorder of unknown etiology, is a significant public health problem. Evidence from studies of phenomenology, comorbidity, family history, and pharmacologic treatment response suggest that fibromyalgia may be associated with major mood disorder, and possibly to a proposed group of conditions known as affective spectrum disorders. Prior psychiatric research has demonstrated that major mood disorder is highly familial. Family history studies provide a method by which to assess how medical disorders co-aggregate in families and, therefore may share a common risk factor or pathophysiologic mechanism. To date, few studies have explored the morbid risk of major mood disorder (and other proposed affective spectrum disorders) in probands with fibromyalgia and their first- degree relatives. All of these studies have used the family history method, which entails interviewing probands regarding their knowledge of psychiatric illness in relatives. Although most of these studies have provided important preliminary data suggesting an association between fibromyalgia and major mood disorder, this method has been demonstrated to be less sensitive in detecting illness in relatives than direct interview (the family interview method). In order to provide further evidence of a relationship between fibromyalgia and major mood disorder, we propose to study the prevalence of psychiatric and rheumatologic disorders in probands with fibromyalgia and their firstdegree relatives as compared to probands with rheumatoid arthritis and their relatives using the family interview method. In addition to assessing the degree of co-aggregation of these disorders within families, we will also study the occurrence of other conditions within the proposed group of affective spectrum disorders in relation to fibromyalgia,
36 Rheumatoid Arthritis
and the association between the severity of fibromyalgia symptoms and the presence of major mood disorder within families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COORDINATE REGULATION OF APOPTOSIS AND CELL CYCLE IN RA Principal Investigator & Institution: Perlman, Harris R. Medicine; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2002 Summary: The work proposed for this grant focuses on the coordinate regulation of proliferation and apoptosis in rheumatoid arthritis (RA). Analysis of human RA synovial tissues (ST) sections revealed increased rates of synovial fibroblast proliferation and low rates of apoptosis, though the functional significance of reduced apoptosis remains to be elucidated. However, analysis of the rates of in vivo proliferation and apoptosis are limited in human-STs as tissue sections were taken late in disease course. Thus, utilization of animal models is vital for an understanding of the molecular pathways of proliferation and apoptosis in RA. Recently, adenoviral mediated delivery of Fas ligand (Ad-FasL), a known apoptotic inducer ameliorated experimental arthritis, suggesting that enhancing the rate of apoptosis by gene therapy may be a potential effective therapy. A caveat to Ad-FasL therapy is that high levels of Fas ligand is cytotoxic to many tissues of the body, thus development of other genes to be delivered to the RA joint is essential. We demonstrated that the anti-apoptotic protein and cell cycle modulator, Bcl-2 was highly expressed in RA compared with osteoarthritis synovial tissues, particularly in the CD68- negative, fibroblast-like synoviocyte population. In order to determine the importance of endogenous Bcl-2, an adenoviral vector expressing a hammerhead ribozyme to Bcl-2 (Ad-Rbz-Bcl-2) mRNA was employed. Ad-Rbz-Bcl-2 infection resulted in reduced Bcl-2 expression and cell viability in synovial fibroblasts isolated from RA-synovial tissues. In addition, Ad-Rbz-Bcl-2induced mitochondrial permeability transition, cytochrome c release, activation of caspases 9 and 3, and DNA fragmentation. These data suggest that Bcl-2 is necessary for synovial fibroblast survival. In this proposal we describe studies to delineate the mechanism of the induction of mitochondrial permeabilty transition following Ad-RbzBcl-2 infection. In addition we will investigate whether adenoviral mediated delivery of the Bcl-2 ribozyme is efficient in ameliorating adjuvant- induced arthritis in rats. The expected outcome is the suppression of AIA through the inhibition of fibroblast proliferation and increased apoptosis. This approach could lead to the development of a new therapeutic strategy for gene therapy in patients with rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITIS
COPING
SKILLS
TRAINING
FOR
EARLY
RHEUMATOID
Principal Investigator & Institution: Keefe, Francis J. Professor and Associate Director; Psychiatry; Duke University Durham, NC 27706 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis and a major health problem. Although medical interventions are being used much earlier in the course of RA, these interventions do not address the challenges of coping with the early stages of this disease. To date, only one, very recent study has evaluated the efficacy of coping skills training (CST) during the early course
Studies 37
of RA. Although its findings suggest CST may be helpful, the study had methodological limitations (e.g. lack of control for attention, relatively short-term follow-up). It also used a traditional CST intervention that did not specifically address the unique challenges posed by the early course of RA. The proposed study seeks to determine whether a comprehensive coping skills training intervention can improve pain, psychological disability, and physical disability in patients with early RA. 225 patients with early RA will be assigned to 1 of 3 conditions: 1) Comprehensive Coping Skills Training, 2) Arthritis Education, or 3) Standard Care. Patients in the comprehensive coping skills training condition will receive training in a variety of cognitive and behavioral coping strategies and training in specific techniques for improving communication, setting short- and long-term goals, and enhancing maintenance. Patients in the arthritis education condition will attend sessions providing them with detailed information on rheumatoid arthritis and its treatment. Patients in the standard care condition will continue to receive the standard medical care provided to RA patients. Measures of pain, physical disability, and psychological disability and traditional clinical outcome measures will be collected pre- and post- treatment and at 6, 12, and 18 months follow-up. A self-efficacy scale and daily measures of coping, life events, mood, and pain will be gathered at each evaluation in order to analyze how these variables relate to long-term outcome. If comprehensive CST is effective, it could lead to new research and a greater integration of CST methods into the medical management of early RA. Future studies could examine whether comprehensive CST alters the long-term disease course of persons with RA. Finally, future studies could examine whether comprehensive CST alters the immune responses of RA patients to daily stressors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CYTOKINE QUANTITATION Principal Investigator & Institution: Finkelman, Fred D. Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 28-FEB-2006 Summary: The importance of cytokines in rheumatic diseases is illustrated by: 1) animal studies that demonstrate an important role for IL-1beta and TNF- alpha in collageninduced arthritis, down-regulation of collagen-induced arthritis by IL-10 and IL-4, and suppression of murine systemic lupus erythematosis by TNF-alpha; and 2) human studies that demonstrate the efficacy of TNF-alpha antagonists in the therapy of rheumatoid arthritis. The Cytokine Quantitation Core will facilitate studies of the roles of cytokines in rheumatic and related immune disorders by making available to members of the research base: a unique assay that allows measurement of in vivo cytokine production real-time PCR for measuring cytokine gene expression a new technique for identifying cytokine-secreting cells without killing these cells standard techniques for cytokine measurement, such as cytokine ELISAs and RNAse protection assays. Research base members have already collaborated on the use of some of these assays to study: 1) the roles of IL-2 and IFN-gamma in the regulation of collageninduced arthritis; 2) TGF-beta regulation of disease in murine models of SLE; 3) IL-4 and IL-10 regulation of human juvenile rheumatoid arthritis; 4) cytokine regulation of host protection against gastrointestinal nematode infections; and 5) regulation of type 2 cytokine responses. The Core will facilitate ongoing collaborations in studies of rheumatic diseases by; increasing the efficiency and economy of apply presently available techniques; promoting the use of these techniques by core group members;
38 Rheumatoid Arthritis
and supporting further development and dissemination of novel and improved techniques for measuring cytokine secretion and cytokine gene expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--INCEPTION COHORT OF RHEUMATOID ARTHRITIS PATIENTS Principal Investigator & Institution: Fries, James F. Professor; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2002; Project Start 08-APR-2002; Project End 31-DEC-2006 Summary: This Core will establish, maintain, and provide access to inception cohorts totaling over 1500 rheumatoid arthritis (RA) patients enrolled within their first year of disease and will follow these patients using standard ARAMIS protocols within full Health Assessment Questionnaire (HAQ) administration each six months, for a period of longitudinal follow-up of nine years. These cohorts are (1) large, (2) broadly representative, (3) geographically diverse, (4) encompass alternative management strategies, (5) contain DNA typing data (DRBI *0401 and *0404), and (6) include standardized central laboratory determination of CRP and Rheumatoid Factor, (7) contain frozen cells and serum for future studies, (8) enable search for causative agents in RA through use of newly available protein micro-array technology on stored serum, (9) consist of consecutively seen patients without exclusions, and (10) be maintained for long-term follow-up, including standardized reading of hand radiographs at 4 and 8 years of disease. The Core tasks builds upon investigator and staff skills at physician and patient recruitment and in maintenance of large data sets over the long- term. These inception cohorts will provide a unique and powerful resource in support of Projects 1, 2, 3 and 4 and for national and international collaborations with other investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--METHODOLOGY AND DATA MANAGEMENT Principal Investigator & Institution: Chang, Roland W.; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001 Summary: The Methodology and Data Management Core is critically important to the success of this MAMDC and its EEHSR Component in particular. The centralized availability of expertise in database and study form construction; data entry, monitoring, and retrieval, and the various analytic techniques used to test hypotheses and control for potential confounders are essential resources for all investigators. The Core has assisted educators, epidemiologists, and health services researchers from several divisions and departments in studying a wide variety of disease and demographic groups including systemic lupus erythematosus, osteoarthritis, juvenile dermatomyositis (JDMS), rheumatoid arthritis, and the elderly. Core resources have been used efficiently because of the economies of scale in addition to excellent coordination with the EEHSR component. Recognizing that newer analytic techniques have become available and more accepted and that this proposal represents an expansion of our work in clinical epidemiology and health services research, this proposed Core is both larger to support a greater volume of work and broader t utilize these new analytic techniques. As a result of the Executive Committee's decision to emphasize longitudinal and cost-effectiveness research, experts in advanced statistical techniques (generalized estimating equation (GEE), classification and regression trees (CART), econometric approaches to controlling selection bias, meta-analysis),
Studies 39
economics, and decision analysis (stochastic tree modeling, continuous- risk utility assessment) have been recruited as Core co-investigators. Clinical Epidemiology has also been formally included within the Core structure. The Core will support the four EEHSR proposals in this grant application and the funded activities of the JDMS registry and Children's Memorial Hospital. It will continue to contribute to the MAMDC research environment by providing data management and methodologic assistance to investigators who engage in arthritis related research. The institution of a EEHSR/Core research conference and enhanced viability and support for health services research on Northwestern University's Chicago Campus will further heighten the Core's influence on the environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--RESEARCH RESOURCES Principal Investigator & Institution: Firestein, Gary S. Professor of Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: The primary goal of this SCOR is to understand how human rheumatoid synovium is maintained in its chronic inflammatory state. This new information will help SCOR investigators propose and develop novel therapeutic interventions. To support these studies, a Research Resources Core will be created to help organize the collection of human clinical material as well as provide specialized support for the in vivo studies involving animal models of arthritis. The project requires human synovial tissue specimens, synovial mononuclear cells, or synovial fluid from patients with established and early rheumatoid arthritis (RA). One purpose of this core is to develop an implement an efficient, timely, and centralized mechanism for the acquisition and distribution of these research materials. Animal models of rheumatoid arthritis have also been used extensively to study the pathogenesis of chronic inflammatory arthritis. Proper conduct and evaluation of these animal models requires specialized expertise to ensure reliable and interpretable results. Therefore, the Core will help coordinate and centralize the efforts of the investigators and provide ready access to experienced investigators in animal models of arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYR61-MEDIATED ANGIOGENESIS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Lau, Lester F. Professor; Molecular Genetics; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a chronic, painful, incurable, and potentially debilitating disease for which effective therapies are still lacking. One of the earliest histopathological features of RA is the increase of blood vessels in the synovium, which is thought to facilitate the infiltration of leukocytes. synovial hyperplasia, and persistent inflammation. Thus. although angiogenesis itself may not be the cause of RA, it can exacerbate the patholobiology of RA. By analogy to studies in tumor biology in which angiogenic inhibitors have been shown to severely restrict tumor growth, it follows that targeting angiogensis in the RA synovium. may be an efficacious therapeutic approach. We propose to study the role of Cyr61, a novel angiogenic inducer. in RA. Cyr61 can also induce expression of matrix metalloproteases (MMPs), enzymes that promote joint destruction. However. the potential role of Cyr6l has not been systematically examined in RA. Our hypothesis is that Cyr6l plays a critical
40 Rheumatoid Arthritis
role in the angiogenic response in RA, and may serve as an attractive therapeutic target in this disease. We seek to evaluate the role of Cyr61 in RA in two specific aims. First, we will assess the correlation between Cyr61 expression and angiogenesis in human RA synovium by in situ hybridization and immunohistochemistry. The expression of Cyr61 in inflammatory arthritis will be investigated further in a murine model of collageninduced arthritis (CIA) using similar approaches. Then we will explore Cyr61 as a potential therapeutic target. We will test whether blockade of Cyr6l function, using monoclonal antibodies or inhibitory peptides, can prevent or ameliorate arthritis and joint destruction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINE REGULATION IN EXPERIMENTAL ARTHRITIS Principal Investigator & Institution: Finnegan, Alison; Professor; Rush-Presbyterian-St Lukes Medical Ctr Chicago, IL 60612 Timing: Fiscal Year 2001 Summary: An imbalance in the expression of Th1 and Th2 type cytokine is implicated in the pathogenesis of rheumatoid arthritis. The correlation between the dominance of the Th1 type inflammatory cytokine, IFN-gamma, over the Th2-type anti-inflammatory cytokine, IL-4, and chronic arthritis suggests that the ration of Th1:Th2 cytokines is important in regulating inflammation. A critical question is whether the ration of Th1:Th2 cells can be changed and whether this alternation leads to long- term suppression of disease. It is important to understand how Th2 cytokines function to suppress arthritis and whether susceptibility and resistance to arthritis is regulated by the balance in Th1: Th2 type cells. In a murine model of inflammatory arthritis induced by immunization with cartilage proteoglycan (PG), susceptible BALB/c mice develop a higher IFN-gamma to IL-4 ratio, whereas resistant DBA/2 mice develop a higher IL-4 to IFN-gamma ration. This balance between Th1 and Th2 cytokines may regulate susceptibility and resistance to disease. Increasing the level of IL-4 by administering IL-4 protects BALB/c mice from the development of arthritis and suppresses the acute symptoms of established disease. Reducing the level of IFN-gamma by a deficient in the Stat4 gene results in a lower incidence and severity of arthritis. Based these observations we hypothesize that arthritis is a Th1 type disease and that shifting the balance to a Th2 type response will lead to long-term suppression of disease. To test this hypothesis we propose in aim one and two to confer either resistance or susceptibility to arthritis by manipulating cytokines. We will neutralize cytokines with mAbs, use mice with disruptions in cytokine genes IFN-gamma, IL-4 and IL-10 and transcription factors, Stat4 and Stat6, and reconstitute cytokine defects with exogenous cytokines. In aim three, the mechanism of suppression by Th2 cytokines will be defined in disease transfer and cell migration studies. As a model to study intervention in humans, Th2 activity will be studied by engraftment of SCID mice with human synovial tissue. In aim 4 as a model for prevention, we will examine study, site- specific delivery of cytokines to the joint by replication deficient adenoviral vectors encoding regulatory cytokines. The overall goal of this study is to advance the successful treatment of arthritis through understanding the role of Th1 and Th2 cytokines in the pathophysiology of arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOKINE REGULATION OF COLLAGEN-INDUCED ARTHRITIS Principal Investigator & Institution: Ortmann, Robert A. Internal Medicine; University of Missouri Columbia 310 Jesse Hall Columbia, MO 65211
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Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Collagen-induced arthritis is a well-studied animal model of human rheumatoid arthritis. An autoimmune process evolves after immunization with heterologous type II collagen in an adjuvant that induces an inflammatory response. The nature of the inflammatory response induced may be as critical as the antigen used, for mouse strains that have been previously believed to be resistant to disease can become susceptible when the immunization protocol is modified. The long-term objectives of this application are to develop an independent program of research that leads to an improved understanding of the etiopathogenesis of inflammatory arthritis based on a clearer characterization of the inflammatory responses necessary for an autoimmune disease to develop. Initially, characterization of immunomodulatory Th2 cytokines in disease progression will be performed. IL-4 and IL-10 deficient mice will be immunized with type II collagen, and the development of arthritis will be monitored. The immune response to collagen will be studied as determined by cytokine and chemokine expression in the absence of endogenous IL-4 or IL-10. The T cell response to antigen resulting from different immunization protocols will also be studied, as differences in the T cell repertoire may be responsible for the presence or absence of disease. T cell receptor V3 gene usage as well as epitope specificity of collagen-reactive T cells will be determined. Levels of collagen-reactive antibodies and binding specificities will be determined to assess the effect on B cell reactivity. Finally, innate immune responses to these immunization protocols will be ascertained. The expression and function of toll-like receptors will be studied by flow cytometry and immunoblotting, and the ability to produce cytokines such as IL-12 and IL-18 under different immunization conditions will be determined. By better understanding unique inflammatory pathways that are required for the development of disease, specific immunotherapy strategies for the treatment of autoimmune processes such as rheumatoid arthritis may be designed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINE-INDUCED ACTIVATION OF SYNOVIAL FIBROBLASTS Principal Investigator & Institution: Fiore, Stefano; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-DEC-2005 Summary: Exaggerated activation of leukocyte immune functions in rheumatoid arthritis (RA) leads to accumulation of inflammatory mediators. The resulting imbalance, with prevalence of inflammatory Thl1 cytokines, contributes to chronic inflammation and tissue damage. A significant role in these processes has been attributed to the recruitment of tissue components, such as the synovial cell lining. For example, cytokine-induced activation of synovial fibroblasts amplifies the cytokine signaling cascade and the release of matrix-degrading enzymes. This contributes to the destructive processes occurring in RA joints. We hypothesize that lipoxins (LX), a novel class of naturally occurring lipid mediators with marked anti-inflammatory actions, activate feedback mechanisms that prevent the exaggerated amplification of these inflammatory processes. We have previously elucidated and cloned a specific LX receptor (LXA4R) that mediates LX anti-inflammatory actions in leukocytes. We recently found that LX functional receptors are expressed in human (hLX! R) and mouse (mLXA4R) synovial fibroblasts. We propose to determine if expression of LXA4R will subject synovial fibroblasts to LX regulatory activities. This goal will be pursue by: 1) characterizing, at the molecular and functional level, LXA4 signaling pathways in synovial fibroblasts; and 2) assessing LXA4 regulatory actions toward cytokine-induced
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activation of synovial fibroblasts. Since, a decrease of the Th2/Th1 cytokines ratio is observed in RA, and Th2 cytokines positively regulate 15-LO gene transcription, a third Aim will evaluate synovial fibroblast 15-lipoxygenase (15-LO) pathway and LX biosynthetic potential. Decreased 15-LO activity can negatively impact the synthesis of 15-LO derived anti-inflammatory eicosanoids, such as LX and 15-hydroxy derivatives of arachidonic acid. Therefore, elucidation of cytokine-dependent regulation-of 15-LO pathways in synovium will elucidate 15-LO pathways and generated mediators in negative feedback loops relevant to the pathophysiology of RA and offer new targets for novel therapeutic strategies. Finally the biology and therapeutic potential of LX will be investigated in twomouse models of inflammatory arthritis: the antigen-induced and the proteoglycan-induced models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DBPA/B PROTEINS OF BORRELIA BURGDORFERI & LYME ARTHRITIS Principal Investigator & Institution: Parveen, Nikhat; Molecular Genetics & Microbiol; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2006 Summary: (provided by applicant): Lyme disease presents a unique clinical system to study cellular and molecular mecahnisms responsible for chronic inflammatory diseases. The disease, caused by the spirochete Borrelia burgdorfen, is the most prevalent arthropod borne disease in the United States. It is a multisystemic illness that affects skin, muscles, joints, heart and nervous system. If left untreated, chronic manifestations are frequenctly observed and Lyme arthritis is the most common symptom in North America. My Iong term qoal is to identify the virulence factors of B. burgdorferi involved in attachment to host cells and in colonization of various tissues, and characterize their role in the pathogenesis, diagnosis and prevention of chronic Lyme disease. Glycosaminoglycans (GAGs), ubiquitously expressed on the surface of all nucleated cells, are recognized by various Lyme spirochetes and several bacterial molecules are involved in this adherence. Decorin binding lipoproteins DbpA and DbpB of B. burgdorferi show affinity for heparin and dermatan sulfate GAGs in addition to the proteoglycan decorin. My hypothesis is that DbpA and DbpB contribute to the colonization of various tissues by B. burgdorferi binding to GAGs and decorin present on the host cells and trigger an inflammatory response in skin and joints causing erythema migrans and Lyme arthritis. The major question to be addressed in this study are: (1) Do DbpA and DbpB contribute to the GAGsmediated attachment of B. burgdorferi to host cells and to the inflammatory response in the joints of susceptible mice? (2) Does deletion of dbpA and dbpB genes affect attachment of B. burgdorferi to the host cells? (3) Are DbpA and DbpB lipoproteins essential virulence factors of B. burgdorferi that trigger Lyme arthritis? Si,qniflcance: Lyme arthritis exhibits several symptoms similar to those of rheumatoid arthritis. However, unlike rheumatoid arthritis, the causative agent is known in Lyme disease and hence, it is feasible to analyze the molecular mechanisms involved in this form of destructive arthritis. In addition, B. burgdorfer/ infected mouse exhibits symptoms similar to those of human Lyme disease, and hence, murine model provides an ideal system to analyze the mechanisms of Lyme borreliosis. This study will characterize the role of two spirochete lipoprotein adhesins in Lyme arthritis in the murine model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DENVER AUTOIMMUNITY CENTER OF EXCELLENCE Principal Investigator & Institution: Kotzin, Brian L. Professor; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 28-SEP-1999; Project End 31-AUG-2003 Summary: The proposed Denver Autoimmunity Center of Excellence combines the efforts of investigators with faculty appointments at the University of Colorado Health Sciences Center. Affiliated institutions include the Barbara Davis Center for Childhood Diabetes, the National Jewish Medical and Research Center, the Children's Hospital of Denver, the University Hospital of Denver, the Rocky Mountain Multiple Sclerosis Center, as well as the Denver Arthritis Clinic. Faculty have been recruited from the Departments of Immunology, Pediatrics, Medicine, Neurology, Dermatology, Pathology, and Preventative Medicine/Epidemiology, and the Human Medical Genetics Program. Within the Departments of Pediatrics and Medicine, subspecialties include endocrinology, rheumatology, clinical immunology, nephrology, pulmonary and gastroenterology. There are unique resources for clinical investigation and strong basic faculty, and in many instances a track record for combining basic and clinical investigation. The proposed Autoimmunity Center includes a strong research and clinical base in type 1 diabetes, celiac disease, systemic lupus, rheumatoid arthritis, multiple sclerosis, autoimmune skin disease, autoimmune pulmonary diseases as well as other autoimmune disorders. One unique clinical resource involves ongoing studies of newborns from both the general population and relatives of patients with type 1 diabetes who are HLA typed using cord blood and then evaluated prospectively for the development of autoantibodies associated with type 1A diabetes and disease A major strength of the current proposal we believe sit he breadth of work in Denver studying T cell recognition and biology, genetics, and the biology of inflammatory and cytokine mediators. In the current proposal, two clinical trials are proposed. Clinical Project 1 will evaluate subcutaneous insulin vaccination to prevent the appearance of anti-islet autoantibodies in infants at high risk for the development of autoantibodies and disease. Clinical Project 2 will test humanized anti-C5 mAbs in patients with active lupus nephritis. The three proposed basic components are: 1) to define the T cell specificities and distribution of insulin- and islet antigen- reactive T cells in murine models and patients with type 1; diabetes; 2) to determine the effects of inhibition of IL-18 and complement on cytokine patients with type1 diabetes; 2) to determine the effects of inhibition of IL-18 and complement on cytokine production and disease in collageninduced arthritis and rheumatoid synovium; and 3) to define the non- MHC genetic contributions to different clinical subtypes of autoimmune polyendocrine syndrome II. The three basic projects will provide important information to design future clinical trials , to monitor the effectiveness of immunologic therapies, and/or provide surrogate markers to correlate with immunologic therapies in autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION AND PRODUCTIVE WORK ACTIVITY Principal Investigator & Institution: Lerner, Debra J.; New England Medical Center Hospitals 750 Washington St Boston, MA 021111533 Timing: Fiscal Year 2001; Project Start 08-SEP-2000; Project End 31-AUG-2004 Summary: (Applicant's abstract): While depression is a leading cause of work disability in this nation, disability reduction efforts remain hampered by a lack of research. This study's long-term goal is to prevent work disability due to depression. A longitudinal study is proposed that addresses on-the-job work disability among employed primary
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care patients with depression. The sample will include 350 patients who have Major Depressive Disorder (MDD) and/or dysthymia and are employed at baseline, and two comparison groups: 1)) 200 workers with rheumatoid arthritis (PA), a physically limiting condition with one of the highest work disability rates; and 2) 100 "healthy" controls. The study has 3 specific aims: 1) to prospectively assess and compare the rates at which four types of work disabilities (job loss, work time loss, reduced work hours and on-the-job limitations) occur among the groups; 2) to identify variables that contribute to successful and unsuccessful work outcomes among patients with depression; 3) to determine whether the variables that contribute to work disability are the same for depression and RA. The project's health-relatedness is its focus on a major public health problem (work disability due to depression) within an increasingly important segment of the mental health care delivery system (primary care). Subjects will be recruited from primary care practices, 18-62 years of age, employed at baseline and not planning to stop working for at least 2 years. Data will be collected from patient surveys (baseline and months 3, 6, 12 and 18), patient charts and clinic pharmacy records. We will also administer a new validated survey instrument; The Work Limitations Questionnaire, which assesses on-the-job performance and productivity and, thus, captures aspects of work disability not reflected in job loss and absenteeism data. The statistical analysis will: 1) establish the magnitude of the four types of work disability and work productivity costs within the depression sample); 2) identify variables that predict work disability or a sustained ability to work; and 3) determine the differential impact of a mental and a physical illness on work disability rates, the predictors of work disability and productivity costs. Study results will contribute to the design of disability prevention and productivity improvement programs and policies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF A BOTANICAL ANTI-ARTHRITIS DRUG, PMI001 Principal Investigator & Institution: Fridlender, Bertold; Phytomedics, Inc. 65 Stults Rd Dayton, NJ 08810 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): An extract of the roots of Tripterygium wilfordii, a plant with a long history of medicinal use in China, demonstrated great promise as a potential prescription botanical drug for rheumatoid arthritis. In-vitro, in-vivo and human clinical studies performed in the U.S.A. and in China indicate that the extract of Tripierygium roots (PMI-001) is effective against arthritis and other autoimmune disorders. PMI-001 contains triptolide and other related molecules that inhibit IL-2 release and COX-2 transcription, a dual mechanism that is unique among current arthritis treatments. The main difficulty to PMI-001 development as a successful botanical drug has been obtaining a supply of roots that are consistent in quantity, quality and efficacy. The proposed work will establish large-scale greenhouse based hydroponic cultivation of Tripterygium in order to optimize PMI-001 safety and efficacy and assure its continuous and cost-effective supply. This will be accomplished through determining optimum conditions for plant propagation, cultivation, harvesting and extraction. In addition, analytical methods and efficacy bioassays will be developed and validated, establishing the framework for the future QAIQC methods and GMP procedures necessary for the FDA approval of this novel, safe and efficacious product. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF THE NORTH CAROLINA RA COHORT Principal Investigator & Institution: Jonas, Beth L.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001 Summary: Rheumatoid arthritis (RA) is a chronic multi system disorder with predominant findings in the diarthroidal joints. Estimates of the prevalence of RA vary from 0.5% in some rural African communities to 5% among some Native American tribes. The clinical manifestations vary tremendously from mild synovial inflammation that is easy to control to a multi system inflammatory disease that progresses despite aggressive immunotherapy. The factors that predict disease severity and disease outcome are poorly understood. Genetic factors, such as the shared epitope, have been shown to play a significant role in disease susceptibility and severity among some Caucasians, but the data in African Americans and other racial groups are weak and variable. There are likely other genes that are important and there are data that suggests that disease expression in RA is multigenic. Little is understood about the role of socioeconomic status, environmental factors and health behaviors in the expression of RA in most populations. Since there are likely multiple genes and these genes may be predictive of the clinical characteristics of the disease, data on genotype is only useful if the disease phenotype is well characterized. One of the weaknesses of much of the research on the immunogenetics of RA is the failure to correlate the genetic data with solid clinical, patient-based information. Comprehensive and complete evaluation of patient-based factors and clinical status will allow us to better understand the meaning of the genotype and allow us to make more rational predictions about disease course and outcome based on the genetic data. In addition, we will have the opportunity to better study the interaction between genetic and environmental factors in the future. The purpose of this project is to develop a prospective, longitudinal, cohort study of RA among residents of North Carolina. The patients will come from the University of North Carolina Rheumatology and Orthopedic Clinics and the 10 Rheumatology practices throughout the state that comprise the participants of the North Carolina Arthritis Health Project. a cohort representative of both tertiary care and community based practices. The major focus of these studies is to determine the role of socioeconomic status, attitudes, health behaviors, and genetics in determining severity and damage in RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISABILITY IN VALUED LIFE ACTIVITIES IN PERSONS WITH RA Principal Investigator & Institution: Katz, Patricia P. Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This project will describe disability in valued life activities (VLAs) among persons with rheumatoid arthritis (RA), as well as factors associated with maintenance of those activities and factors that may protect against negative psychological outcomes following VLA disability. The same physical manifestations of RA that may cause difficulty in mobility or in performing a self-care activity may also cause difficulty in more complex, discretionary activities such as hobbies or socializing with friends. The wide range of activities that individuals find meaningful or pleasurable, above and beyond activities necessary for survival or selfsufficiency, is what we term "valued life activities". Performance of VLAs appears to be linked to psychological well-being and satisfaction with function. Although loss of
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VLAs has been found to be a risk factor for the onset of depressive symptoms, effects of difficulties in VLA performance are not known. Also, many individuals who lose the ability to perform VLAs do not develop depressive symptoms; factors that protect individuals from psychological distress after VLA disability have not been identified. This study will estimate VLA disability and identify factors associated with maintenance of VLAs, psychological outcomes of VLA disability, and factors associated with maintenance of psychological well-being after VLA disability, building on the Verbrugge and Jette disablement process model. Subjects will be queried about these topics in annual telephone interviews. Items to assess VLA disability and psychological outcomes will be included in the interview, as well as questions about potential risk and protective factors for VLA disability and psychological distress. These items will consist of existing scales and survey items when available, and items developed specifically for this study. Analyses based on the study model (Figure 1) will focus on 3 major areas: (1) description of VLA disability among individuals with RA over a 5-year period, (2) description of psychological outcomes of VLA disability, and (3) identification of factors associated with maintenance of VLAs and maintenance of psychological well-being after VLA disability. Mathematical models will be developed to describe these relationships in the context of the study model, using both cross-sectional and longitudinal analyses. The findings from this study will provide information that may help minimize VLA disability and the psychological distress that might result from VLA disability, thereby improving quality of life of persons with RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISABLEMENT PROCESS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Escalante, Agustin; Associate Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-MAY-2004 Summary: (adapted from investigator's abstract): The broad objective of this research is to understand disability in rheumatoid arthritis (RA) within the theoretical framework of The Disablement Process Model. This model postulates a main disease-disability pathway in which pathology causes impairments, which lead to functional limitations, which, in turn, cause disability. Risk factors that precede and interventions or exacerbation's that follow the onset of the process of disablement, modify the main pathway. The specific aims of this application are: (1) To define the temporal sequence of events in the development of disability due to RA attributable to altered articular structure; (2) To define the temporal sequence of events leading to disability in RA attributable to pain; (3) To define the temporal sequence of events leading to disability in RA attributable to symptoms of depression; (4) To evaluate the modifying effect of medical interventions and co-morbidity. The models and hypotheses of this application are based on cross-sectional analyses on a cohort of 455 persons with RA participating in Dr. Escalante's current ORALE Study (Outcome of Rheumatoid Arthritis Longitudinal Evaluation). The ORALE cohort will be augmented to 760 members by the end of the first year of this application. Four yearly follow-ups are planned after the initial baseline assessment, to be conducted during the first through fourth years of this 5-year application. Main pathway factors that will be assessed include the inflammatory response, serum rheumatoid factor, bone destruction and extra-articular signs and symptoms, corresponding to pathology; articular signs and symptoms, strength, ambulation and manual dexterity, corresponding to impairments; activities of daily living, under functional limitations; and physical disability. Risk factors are age, gender and ethnicity, the HLA-DRB1 genotype, education, occupation, income, functional
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health literacy and acculturation. Psychosocial modifiers include and social support, learned helplessness, self-efficacy, coping strategies, stress, symptoms of depression, and coexistent medical conditions. Interventions to be measured include anti-rheumatic drugs and joint surgery, the lag between disease onset and initiation of anti-rheumatic therapy, compliance, and rehabilitation interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIVERSITY OF T LYMPHOCYTES IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Goronzy, Jorg J. Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 20-DEC-1993; Project End 31-MAR-2002 Summary: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a progressive destruction of the joint architecture. CD4+ T cells are likely to have a central role in promoting the synovial inflammation as well as the extraarticular spreading of the disease. Recent studies have led to the model that the global repertoire of CD4+ T cells is important in setting the stage for the inflammatory response. RA patients have several unique features of the CD4+ T cell repertoire. First, the repertoire of CD4+ T cells is influenced by the disease associated HLA-DRB1 polymorphism. Second, RA patients have a different BJ gene segment usage in the naive CD4 population compared to HLA matched controls, suggesting the existence of a genetic risk factor which is involved in BV-BJ gene recombination and/or thymic selection. Third, RA patients carry CD4+ T cells which undergo clonal expansion in vivo. Clonogenic CD4+ T cells recognize self antigens with a wide tissue distribution and are more resistant to apoptosis inducing stimuli. They lack the major costimulatory molecule, CD28, but are dependent on alternate costimulatory signals to proliferate and to escape anergy induction. It is the hypothesis of this proposal that these alternate costimulatory signals facilitate the proliferation and clonal expansion of autoreactive T cells in RA patients and that effector functions mediated by these clonogenic T cells contribute to synovial inflammation and to extra-articular disease. In the first specific aim, we will analyze how the different unique features of the T cell receptor repertoire of CD4+ T cells in RA patients are related and whether thymic selection mechanisms predispose patients to generate CD4+ CD28- autoreactive T cells. In the second specific aim, we propose to identify the costimulatory pathways in CD4+ CD28- T cells. These alternate costimulatory signals may be responsible for the defective downsizing of these T cells in vivo and for their resistance to apoptosis inducing signals in vitro. We propose to analyze pathways which are known to be important in controlling lymphoproliferation, to determine whether these pathways are intact in CD4+ CD28- T cells and to determine how they are regulated by the alternate costimulatory molecules. Finally, we have designed experiments to characterize effector functions of CD4+ CD28T cells and their dependence on costimulatory signals. In combination, these approaches will allow us to determine how autoreactive CD4+ CD28- T cells are clonally expanded in RA patients and how they function in the rheumatoid inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DNA VACCINE MEDIATED IMMUNOTHERAPY OF RHEUMATIC DISEASE Principal Investigator & Institution: Robinson, William H. Neurology & Neurological Scis; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005
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Summary: My career goal is to develop treatments for patients with devastating clinical immune disorders. During the time of this award, with Dr. Lawrence Steinman as my mentor I propose to develop selective immune therapy for an animal model of rheumatoid arthritis (RA). RA is a chronic autoimmune inflammatory synovitis affecting 1 percent of the world population. Using collagen-induced arthritis (CIA) in mice as a model for RA and DNA vaccination as a tool for generating and modulating immune responses, I propose to answer several questions pertaining to therapeutic immunization against CIA. I will also develop and study peptide pulsed peripheral monocytes for therapy of CIA and autoimmunity. I will address the following specific aims: (1) Can we protect against CIA by injection of DNA encoding: (a) the Vbeta8.2 region of the T-cell receptor, (b) collagen or collagen peptide, and (c) tandem DNA constructs encoding collagen, collagen peptide, or Vbeta8 TCR plus Th2 promoting cytokines including IL-4, IL-10, and TGF-beta? (2) We will examine the mechanisms of DNA vaccine-mediated protection against CIA using (a) cytokine assays, (b) flow cytometry, (c) soluble tetrameric major histocompatibility complex class II-peptide complexes, (d) T cell proliferation assays, (e) bone marrow chimeric mice, and (f) DNA microarrays. (3) Can we protect against CIA by injection of collagen peptide pulsed peripheral monocytes? These experiments will be carried out at the Stanford University Beckman Center. During the course of the proposed award period the candidate will continue to practice clinical Rheumatology on a 10 percent basis and take formal coursework in immunology and the ethical conduct of research. The overall goal of the proposed training program is to prepare this candidate to establish an independent laboratory in an academic division of Rheumatology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY AGGRESSIVE TREATMENT OF POLYARTICULAR JRA Principal Investigator & Institution: Wallace, Carol A.; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, WA 98105 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): This is a 2-part application. PART 1: An abbreviated protocol for a randomized actively controlled trial of early aggressive therapy in polyJRA. PART II: A plan for development of essential components for the trial's conduct. PART 1: The overall goal of this trial is to improve the physical functional ability and health related quality of life outcomes of children with poly articular juvenile rheumatoid arthritis (poly-JRA). Specific Aim: To compare the efficacy and safety of an aggressive treatment regimen initiated within the first 6 months of disease in children with poly-JRA to that of the current standard-of-care in producing a state of complete clinical response and improve outcome via a randomized, open trial 6 months in duration. Primary hypotheses are: 1) That aggressive therapy initiated within 6-months of poly-JRA disease onset will result in a higher proportion of children entering a state of complete clinical response as compared to the proportion of children who achieve such a response by use of the current standard-of-care after 6 months of therapy. 2) That early aggressive therapy will result in better physical./functional ability as compared to the current standard-of-care after 6 months of therapy. 3) That early aggressive therapy will result in higher health related quality of life as compared to that produced by the current standard-of-care after 6 months of therapy. PART 2: The overall goal is to develop a written plan for the execution of the clinical trial described in PART 1, and to secure funding for the effort to allow commencement of the trial. SpecificAim 1: To determine by questionnaire survey the barriers to the effective participation in trials by the clinical sites involved in this trial as well as other potential sites, including ability to
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open for patient enrollment in an expeditious manner, recruitment of study participant, follow-up, case report form completion. Specific Aim 2: To convene a meeting of senior investigators, methodologists, and regulatory personnel to develop strategies for overcoming the barriers identified in Specific Aim 1. Specific Aim 3: To develop criteria for defining one of the primary outcome variables, complete clinical response, and the related term, clinical remission, to be used in the proposed trial. Specific Aim 4: To prepare and submit an application to fund the clinical trial described in PART 1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETANERCEPT THERAPY IN FOLLICULAR LYMPHOMA Principal Investigator & Institution: Freedman, Arnold S.; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 12-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Although several novel therapeutic approaches have been developed for treatment of follicular lymphomas (FL), the overall survival has not yet been significantly improved. In vitro studies have provided evidence that FL cell survival is influenced by signals from the neoplastic microenvironment. FL cells associate with stromal elements known as follicular dendritic cells (FDCs), which provide anti-apoptotic signals to FL cells and chemotactic factors that likely contribute to the localization of FL cells within lymphoid follicles. Since FDCs provide survival and homing signals to lymphoma cells, targeting these cells in the microenvironment may be a novel treatment approach for FL. TNF( is overexpressed by FL cells, and TNF( upregulates the expression of adhesion molecules, cytokines and chemokines which are critical to FL cell-FDC interactions. Etanercept is a soluble, dimeric, recombinant human p75 TNFR, fused to the Fc fragment of human IgG1, developed for neutralization of TNF( and is an approved therapy for rheumatoid arthritis with an favorable toxicity profile. We hypothesize that TNF( blockade will affect the tumor microenvironment and therefore alter FL celI-FDC interactions, and FL cell survival. To investigate this hypothesis we propose three specific aims. First, to undertake a clinical trial of etanercept for patients with relapsed FL. Second, to investigate effects of etanercept on the tumor microenvironment directly and indirectly through studies of surrogate markers. We will investigate effects on FDCs, surrogate peripheral blood and serum markers as well as utilize PET scanning to assess the potential biologic activity of etanercept. Third, to investigate the effects of etanercept on T cell activation. Since TNF( is important in T cell function, it will be important to understand the effects of etanercept on T cells in these patients. This study is a novel approach to treating FL, where targeting the microenvironment of the tumor may inhibit the growth and survival of the neoplastic cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAS FIBROBLASTS
LIGAND
GENE
TRANSFER
APOPTOSIS
SYNOVIAL
Principal Investigator & Institution: Zhang, Haidi; Div/Pharmaceutics/Indust Pharm; Long Island University Brooklyn Campus Brooklyn Campus New York, NY 11201 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 30-JUN-2005 Summary: (provided by the applicant): Rheumatoid arthritis (RA) is characterized by hyperplasia of synovial membrane and bone destruction. Fibroblast-like synoviocytes play an important role in the pathogenesis of rheumatoid arthritis because of their proliferation and secretion of an impressive array of cytokines/chemokines, adhesion
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molecules, and proteases, which result in the progressive bone and joint destruction. Synovectomv is a surgical approach to remove the inflammatory synovium, ameliorate the inflammation and delay the progress of joint destruction. An efficient medicallyinduced programmed cell death (apoptosis) in the inflammatory synovium might play a role similar to synovectomy but without surgical tissue damage. The proposed research project focuses on developing the "FasL gene scalpel" for the replacement of the synovectorny for the treatment of rheumatoid arthritis and other arthropathies. This project simplifies the current problems of gene delivery, gene target and gene expression regulation in human gene therapy. The induction of apoptosis in the inflammatory synoviocytes is the main purpose of FasL gene transfer intra-articularly. A transient, localizable, immune tolerance and dose dependent gene transfer may be achieved by a direct intra-articular injection of the FasL gene carried by a suitable vector which infects synoviocytes but not chondrocytes in cartilage. To carry out this purpose, they have investigated the effects of FasL gene transfer on the human RA synovium. The results showed that the fibroblast-like synoviocytes can be infected by adenovirus-FasL as well as undergo apoptosis after infection in a dose-dependent fashion and that the inflammatory synovium from RA patients can be eliminated in situ in a RA-SCID mouse model by a repeated local administration of adenovirus vector mediated FasL gene transfer. In this application, they propose to produce an adenovirus carrying human Fas Ligand gene and GFP in the same vector to examine whether FasL gene transfer in human RA synovium in SCID mouse model in vivo through the mechanism of "bystander effects." If the bystander effects exist in FasL gene transfer into synovium, it would be possible to carry out a therapeutic level of gene transfer with non-viral vector and lower dosage of DNA. They are going to investigate the possible side effects involved in FasL gene transfer into synovial fibroblasts and synovium, such as induction of pro-inflammatory cytokines/chemokines production as well as their correlation with Fas/FasL interaction, in order to find an approach to control them. They will identify the effects of the long term, multiple FasL gene transfer on the viability and metabolism of chondrocytes in vivo. This is an important factor to evaluate the clinical potential of the FasL gene scalpel. The above studies could elucidate clinical potential and possible side effects of FasL gene transfer intra-articularly, and have a high likelihood of being translated into a novel approach for treating arthritis patients at the inflammatory site. The long-range goals are the development of a novel therapeutic approach--"Gene Scalpels" for arresting inflammatory synovium at an early stage of arthritis by intra-articular administration of an apoptosis inducer, such as FasL, using a suitable vector system, which may replace synovectomy for some arthritis patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAS LIGAND GENE TRANSFER IN ARTHRITIS Principal Investigator & Institution: Chen, Youhai H. Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2002 Summary: (Adapted from the applicant's abstract) - Rheumatoid arthritis and related animal models are inflammatory diseases of the joints mediated by activated synovial cells and infiltrating bone marrow-derived cells. The long-term goal of research of the investigators is to eradicate the arthritic inflammation by somatic gene transfer. They hypothesize that intra-articular Fas-ligand gene transfer may convert an otherwise inflammatory joint into an immune privileged organ by inducing apoptosis of activated synovial cells and by deleting antigen-specific lymphocytes. To test this hypothesis they have developed four specific aims: 1). To study Fas-mediated apoptosis in the arthritic
Studies 51
synovium following adenoviral vector-mediated FasL gene transfer. The kinetics of apoptosis of both fibroblast-like synoviocytes and bone marrow-derived synovial cells will be studied; 2) to determine the frequencies and functions of collagen-specific lymphocytes in arthritic animals injected with FasL virus. Intra-articular expression of FasL may induce type II collagen-specific immune tolerance by selectively depleting collagen-specific lymphocytes. Thus, intra-articular injection of FasL virus may prevent the development of arthritis in other joints. This will be investigated by determining the frequencies and functions of collagen-specific TH1, TH2 and B cells in and outside of the arthritic synovium; 3) to determine the frequencies and functions of vector-specific lymphocytes in arthritic animals injected with FasL virus. Intra-articular FasL gene transfer may also induce apoptosis of vector-specific lymphocytes and help diminish the immune barrier impeding viral vector-mediated gene therapy. This will be investigated by examining the frequencies and functions of vector-specific lymphocytes in and outside of the arthritis joints and by monitoring the lengths and levels of transgene expression in vivo; 4) to study FasL gene transfer in spontaneous autoimmune arthritis. If FasL gene transfer eliminates activated synovial cells that mediate arthritic inflammation, it should be effective in diminishing arthritis regardless of its etiology or initiating antigens so long as the disease is mediated by activated synovial cells expressing the Fas molecule. To test this theory, they will study FasL gene therapy in a spontaneous arthritis model in which systemic autoimmunity leads to joint-specific inflammation. Information generated from these studies may help elucidate the mechanisms by which FasL gene transfer diminishes autoimmune arthritis and may lead to the development of a novel strategy for treatment of autoimmune arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION AND DIAGNOSIS OF AUTOIMMUNE DISEASE Principal Investigator & Institution: Aune, Thomas M. President; Arthrochip, Llc 117 Bromley Park Ln Franklin, TN 37069 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 14-FEB-2004 Summary: (provided by the applicant): Autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes, and multiple sclerosis, are thought to arise from abnormalities of innate or adaptive immune responses. Autoimmune diseases are often difficult to diagnose, as the symptoms can be typical of other conditions and quite vague, such as musculoskeletal complaints and pain, headaches or dizziness. No available blood test can accurately exclude the possibility of an autoimmune disease in a subject with these symptoms. At best, a battery of tests and a period of observation are usually required to establish that a patient does in fact have an autoimmune disorder. Thus, a single test that could readily exclude the possibility of an autoimmune disease would allow physicians to focus their efforts on patients who have the greatest likelihood of serious disease. Using microarray technology, we have compared differences in gene expression in peripheral blood mononuclear cells among individuals with four distinct autoimmune diseases, normal control individuals before and after immunization, and individuals with other chronic diseases. Surprisingly, we find that each individual with autoimmune disease has a common gene expression signature that is independent of the specific autoimmune disease but is totally distinct from the normal immune response and is not observed in individuals with other chronic diseases. Based upon these observations, we have developed a simple test for excluding the possibility that a subject has an autoimmune disorder. The main advantage of this test is that it is a quicker and more accurate test than those currently available. This test has thus far predicted autoimmune patients from normal patients with 100 percent
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accuracy. The first goal of this proposal is to collect gene expression data from a sufficient number of individuals to design a test with optimal predictive power. The second goal is to validate the test by examining a cohort of individuals who do not yet carry a clear-cut diagnosis of an autoimmune disease. Long-term goals are to use results from microarray experiments to develop tests that have predictive value for the therapeutic management of individuals with autoimmune diseases. These include tests that classify diseases, predict severity, and predict the best therapeutic options. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE ACTIVATION
EXPRESSION
PROFILES--JRA
AND
MACROPHAGE
Principal Investigator & Institution: Grom, Alexei A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2003; Project Start 22-AUG-2003; Project End 31-JUL-2008 Summary: This project will focus on gene expression profiles in the systemic form of Juvenile Rheumatoid Arthritis. Specific Aim 1 will focus on the gene expression profiles that will distinguish patients with systemic JRA from other clinical forms of the disease, and identify patients bound to develop progressive erosive arthritis at later stages of the disease. Specific Aims 2 and 3 will focus on Macrophage Activation Syndrome and its relationship to clinically similar familial hemophagocytic lymphohistiocytosis (FHLH). MAS is a well recognized life-threatening complication of soJRA. As in FHLH, its development is associated with uncontrolled expansion of T-cells and macrophages. The pathogenesis of FHLH has recently been associated with decreased natural killer (NK) and cytotoxic cell functions secondary to mutations in the gene encoding perforin. All MAS patients included on our preliminary studies had profoundly depressed NK function suggesting that this abnormality is likely to be central to the development of MAS as well. Moreover, patterns of perforin expression in some of the MAS patients were similar to those in FHLH carries. Therefore, in Specific Aim 2 we will assess the extent of NK dysfunction in soJRA and identify gene expression profiles associated with this particular immunologic abnormality. Specific Aim 3 will focus on the changes in the gene expression profiles specific to the acute phase of MAS and FHLH themselves rather than the underlying immunologic abnormalities. We expect that the comparison of the obtained expression profiles should clarify the relationship between MAS and HLH, a better understood disease with a known genetic defect. The long-term goal of this proposal to define the pattems of immune gene dysregulation which leads to the development of soJRA and MAS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR TREATMENT OF AUTOIMMUNE DISEASES Principal Investigator & Institution: Melo, Marco; American National Red Cross Rockville, MD 20855 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 28-JUN-2002 Summary: The goal of this proposal is to introduce a novel gene therapy approach for reversing progressive autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. Initial studies will emphasize animal models in which disease producing epitopes have been identified. The rationale is based on the finding that adult mice injected i.v. with bone marrow or peripheral cells expressing bacteriophage lambda cI epitope 12-26 in frame with an IgG carrier become profoundly tolerant to this determinant at both the B and T cell levels. This state of unresponsiveness can be
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induced in previously immunized animals. Since the bone marrow-derived cells in the periphery continue to produce and present the tolerogenic epitopes to newly generated T cells, the experiments proposed herein will offer an opportunity to both induce and maintain tolerance to autoantigens by host antigen presentation. My hypothesis is that B cells are tolerogenic APC and that this protocol favors B cell presentation. Retroviral vectors, constructed to express myelin basic protein or collagen epitopes on an IgG scaffold, will be used to infect bone marrow and peripheral hematopoietic progenitor cells, which will then be injected into adult mice before and after induction of experimental allergic encephalomyelitis (EAE) or collagen induced arthritis. The aims of this project are: 1) To develop novel genetically-engineered constructs for the expression of myelin basic protein (MBP) and its immunodominant determinants as part of an IgG tolerogenic carrier. 2) To test the efficacy of these novel constructs to abrogate the immune response to MBP in susceptible strains in order to prevent and treat EAE. 3) To optimize this protocol for transfection into long-term bone marrow cultures containing B cell precursors for transfection with these constructs. 4) To test if our findings in the EAE model can be applied to another autoimmune models, e.g., collagen induced arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY TO PREVENT AUTOIMMUNE DISEASE Principal Investigator & Institution: Fathman, C Garrison. Professor; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 14-AUG-2006 Description (provided by applicant): We hypothesize that autoimmune diseases progress through several (at least two) "checkpoints", an early inflammatory and late phase destructive disease. We believe it might be possible to design common "prevention" strategies to arrest disease progression in one or both of these phases by the following. (1) Autoantigen reactive CD4+ T cells transduced with retroviral vectors to express "regulatory proteins" may provide tissue specific immunotherapy through the expression of the regulatory proteins at the site of autoimmune inflammation. (2) FcR non-binding anti-CD3 and anti-TNF antibodies might block disease progression. We plan to study the non-obese diabetic (NOD) mouse, that spontaneously develops insulin-dependent diabetes mellitus (IDDM) and shows many of the characteristics of human IDDM, and collagen induced arthritis (CIA) in the DBA/l mouse model, which shares certain characteristics of human rheumatoid arthritis (RA), to attempt these "disease prevention" strategies. We will use the antigen specific properties of autoantigen reactive T cells to develop an adoptive immunotherapy protocol to study the potential of one (or combinations) of various "regulatory" proteins to prevent both of these diseases. We will study the "anti-inflammatory" cytokines, IL-10 and IL-4, an antagonist of a "pro-inflammatory" cytokine receptor, IL-12 p40, and compare local delivery by retroviral transduction of auto antigen specific T cells with SC fV constructs of anti-CD3 and anti-TNF antibodies, to systemic use of the parent antibodies, in these two animal models, singly and in combinations. Additionally, we plan to analyze potential mechanistic effects of anti-CD3 on antigen reactive T cells compared to costimulatory blockade by looking at the expression of a novel anergy specific gene, GRAIL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC ARCHITECTURE OF AUTOIMMUNE DISEASES Principal Investigator & Institution: Kantor, Aaron B.; Surromed, Inc. 2375 Garcia Ave Mountain View, CA 940431104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Phenotypic and genetic markers are urgently needed in autoimmune diseases for early and accurate diagnosis and monitoring disease progression and therapeutic intervention. We are proposing comprehensive phenotypic analysis for the identification of biological markers and genetic mapping of these quantifiable inheritable traits. Rheumatoid Arthritis (RA), a chronic inflammatory disorder that preferentially affects women will serve as a model disease. This application describes SurroMed's comprehensive phenotyping platform and the power of genetic analysis conducted at Myriad Genetics using a rich resource of family material. Phase I focuses on recruitment of RA multi-case families, technology development, and an initial analysis of human serum from affected RA family members and unaffected first-degree relatives. The approach includes both broad discovery-based and hypothesis-driven strategies. We will test the hypothesis that there are multiple quantitative differences in cellular and serum phenotypic variables between RA subjects and unaffected first-degree relatives. If our efforts are successful, in Phase II, we will test the hypothesis that variation in the levels of multiple biomarkers are significantly inheritable. Potential results of the work include biomarker and genetic products for the clinical assessment of disease. The methods developed here will also be broadly applicable to other conditions, especially autoimmune and immunological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC POLYMORPHISMS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Matteson, Eric L.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): About one-third of patients who have rheumatoid arthritis (RA) develop symptoms of inflammation outside the synovium, so-called extra-articular manifestations (ExRA), such as pericarditis, pleuritis, interstitial lung disease, Felty's syndrome, scleritis, keratitis, and vasculitis including mononeuritis multiplex as well as vasculitis involvement of internal organs, and the central nervous system. ExRA manifestations have been reported to occur mainly in patients with severe articular disease and are associated with an excess morbidity for disease related and other conditions, and increased mortality. Suggested predictors of ExRA features include genetic, clinical and serologic factors. The highest frequencies of RA-associated HLA-DR molecules are seen in patients with extraarticular RA. This study seeks to identify genetic risk factors predisposing patients who develop ExRA. Special emphasis will be put on the effect of different HLA polymorphisms and allelic combinations on the targeting of RA to different organ systems. The specific aims are to: 1. Expand a DNA bank from patients and ethnically matched controls to create the facility for large scale association studies in RA. The genetic information from the DNA bank will be linked to a database of clinical parameters collected during long-term follow-up of RA patients seen at Mayo Clinic. 2. Evaluate the impact of a series of candidate genes on the clinical phenotype of RA, including HLA class I genes, HLA class II genes and polymorphisms of inflammatory cytokines. 3. Assess the use of phenotypic immunologic markers as predictors of the clinical course of RA including deficiency for CD28, and aberrant expression of CD158 and 161 on T lymphocytes. The long-term goal
Studies 55
is to establish profiles of genetic risk determinants associated with different patterns of RA to eventually be used as biomarkers in risk assessment and clinical management. This proposal is meant as the cornerstone for a long-term investigative initiative into the nature of RA, and will provide the resources and foundation for the development of a series of clinician-investigators at the beginning of their careers. The mentorship program proposed in this grant is critical to this long-term goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC TRAITS OF SIBLING PAIRS W/ RHEUMATOID ARTHRITIS Principal Investigator & Institution: Pisetsky, David S.; Duke University Durham, NC 27706 Timing: Fiscal Year 2001 Summary: Rheumatoid Arthritis (RA) is a complex polygenic disorder. On the basis of twin and family studies, it is likely that anywhere from three to ten different genes may be involved in this disease. Only one of these genetic regions, located in the HLA complex on chromosome 6, has been defined. A major challenge for researchers is to identify the remaining regions which are involved in predisposition to RA. The purpose of this contract is to identify 1000 families in which two or more siblings are affected with rheumatoid arthritis. Detailed clinical information on affected siblings will be obtained and entered into a database. In addition, hand x-rays, serum and peripheral blood DNA will be obtained from each affected sibling. DNA will also be obtained from the parents of these siblings, when available. This database, serum and DNA repository will form a resource for the entire scientific community to allow for a comprehensive analysis of genetic susceptibility to rheumatoid arthritis. Access to the database and DNA repository by qualified scientists will be governed by an oversight committee. PROGRESS TO DATE: Study enrollment began in November 1997 with a projected endpoint of July 31, 1999. Twenty eight families have been enrolled including 48 females and 16 males. Two families were withdrawn from the study because only one sibling was found to meet study criteria. Study visits have been completed for 16 families with 13 visits completed on the GCRC. Subjects have been recruited by physicians at DUMC and VA Medical Center in Durham, by notifying the Duke Affiliated Rheumatology Trials Consortium (DART) members, mailings to Rheumatologists in North Carolina, South Carolina and Florida requesting patient referrals, and participation in a national toll-free information line for prospective participants. The advertising campaign includes advertisements in Athritis Today, the National Arthritis Foundation Magazine and additional publicity provided by the National Institutes of Health. There are no preliminary results to date. SIGNIFICANCE: This study will help elucidate the genetic causes of rheumatoid arthritis. In addition, the following resources will be available at the conclusion of the study: a) family trees from at least 1000 families with two or more sibs with RA, without personal identifiers and b) DNA samples from affected sib pairs and their parents (when available). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS ANALYSIS OF RA SIB PAIRS Principal Investigator & Institution: Gregersen, Peter K. Professor; North Shore University Hospital 300 Community Dr Manhasset, NY 11030 Timing: Fiscal Year 2001; Project Start 05-JUL-1997; Project End 30-JUN-2005
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Summary: (provided by applicant): This application is a competitive renewal of a project which has the overall goal of identifying susceptibility genes for rheumatoid arthritis which lie outside of the major histocompatibility complex (MH( We have completed a genome wide screen for allele sharing on an initial population of 300 affected sibling pairs with RA. We have identified five markers with evidence of linkage at the p
Project Title: HEART DISEASE IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Gabriel, Sherine E. Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's Abstract) The hypotheses to be tested in this proposal are built on findings from two intriguing, but rather disparate lines of investigation. The first is the recent data suggesting that the excess mortality experienced by people with rheumatoid arthritis (RA) may result from increased rates of coronary heart disease (CHD) among RA patients compared to the general population. The second is the rapidly growing body of evidence indicating that chronic systemic inflammation (such as that which occurs in RA) plays an important role of chronic inflammation in CHD. We propose 3 specific aims to investigate this subject: First, we will use a cohort study to test the hypothesis that the incidence of acute MI (the central manifestation of CHD) is higher in RA subjects compared to controls. Second, we will identify high-risk RA subgroups and, using a novel adaptation of the case-cohort design, investigate interactions between RA and the major CHD risk factors (e.g. smoking, hyperlipidemia, exogenous estrogens). Third, we will conduct studies on archived autopsy heart tissue to test the hypothesis that coronary atherosclerosis is more extensive in RA subjects compared to matched controls. A unique set of circumstances allows us to address each of these aims rigorously and efficiently. We will incorporate and extend our already assembled population-based RA incidence cohort and identify validated definite acute MI outcomes using the cardiovascular surveillance techniques developed through out NIH-funded companion study, "Coronary Disease Morbidity and Mortality in a Population" (HL59205). Our population-based data resources, with essentially complete
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enumeration of a geographically defined population, allowed us to design an analytic plan which nearly quadruples the statistical power of our risk factor analyses, compared with typical cohort analyses. Third, the availability of extensive autopsy material (the autopsy rate in this community is four-fold higher than the national rate and all autopsies have been performed at the same center since 1930) provides us with a unique opportunity to assess the pathologic characteristics of atherosclerosis among RA subjects compared to controls. When combined with our experienced multidisciplinary investigative team, these resources lend us a capability, not available elsewhere, to rigorously examine the risks and determinants of coronary heart disease in patients with RA. These results will lay the foundation for a program of research aimed at elucidating the mechanisms for CHD in RA patients and at improving our understanding of the role of inflammation in the pathogenesis of CHD in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAPY
HIPPOCAMPAL
FUNCTION
DURING
CORTICOSTEROID
Principal Investigator & Institution: Brown, E Sherwood. Assistant Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract) This Mentored Clinical Scientist Development Award (MCSDA) application defines a training program to facilitate the development of the Pl as an independent researcher in the area of mood disorders. The educational activities outlined will enable the Pl to explore the biological basis of corticosteroid effects on brain function. During the course of this award, Dr. A. John Rush will serve as the PI's mentor. Additional experts providing instruction and training include: Drs. Frederick Petty (clinical trials), Bruce S. McEwen (glucocorticoids and the hippocampus), and Alan Frol and C. Munro Cullum (cognitive neuroscience). Measurement of hippocampal volumes from MRI scans will be performed by Dr. John Csernansky's group at Washington University. The training entails increasing the PI's knowledge of neuropsychological testing and clinical research methodology. The Pl plans to use cognitive testing to develop a paradigm in humans for exploring pharmacologic interventions which may prevent or reverse hippocampal changes associated with corticosteroids. In order to achieve the stated training goals, the Pl has developed a program that includes didactic courses, tutorials, and a research project. The proposed project will afford a hands-on experience, reinforcing the information and techniques learned through mentoring and classroom environments. The Pl will first examine memory, mood, and hippocampal volume in asthma and rheumatoid arthritis patients receiving chronic oral prescription corticosteroid therapy, a population the Pl has actively researched for over three years. In animals, agents which inhibit the release of glutamate appear to prevent and reverse hippocampal damage secondary to corticosteroids. Thus, the first experiment in the training plan will be followed by a clinical trial of the glutamate release inhibitor, lamotrigine, to determine if neurocognitive changes associated with corticosteroids can be reversed in humans. Through this award, the Pl will extend his previous research experience by adding new skills and knowledge which will be used for investigations at the interface of neuroscience and clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HLA SUSCEPTIBILITY GENES IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Nepom, Gerald T. Director; Benaroya Research Inst at Virginia Mason 1201 9Th Ave Seattle, WA 98101 Timing: Fiscal Year 2001; Project Start 25-SEP-1994; Project End 31-JUL-2004 Summary: Genetic associations between rheumatoid arthritis and specific HLA class II genes provide clues to understanding the molecular basis for disease susceptibility. There is a remarkable structural relationship among different RA susceptibility genes, in which each of the associated class II alleles encodes a sequence of key amino acids termed the "shared epitope." In this proposal, we outline mechanistic models to account for the shared epitope association with RA, and interpret these models in the context of an HLA-directed pathway for the development of disease. We propose to test specific hypotheses developed from these alternative models, through a series of aims which will characterize the structural basis for TCR recognition of the shared epitope region, identify altered T cell activation resulting from recognition of shared epitope, and investigate and test mechanisms by which the shared epitope may be involved in the generation or modulation of self-recognition during antigen presentation and processing. We propose that the shared epitope association with RA is not solely based on a specific peptide binding motif and peptide determinant selection, but rather is influenced by a strongly biased direct recognition of shared epitope residues by direct T cell contact. The implications for T cell development, selection, and activation will be tested using a combination of human T cell clones and murine transgenic animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HLA-DP PREDISPOSITION
SEQUENCE
POLYMORPHISM
AND
DISEASE
Principal Investigator & Institution: Erlich, Henry A. Senior Scientist; Children's Hospital & Res Ctr at Oakland Research Center at Oakland Oakland, CA 94609 Timing: Fiscal Year 2001; Project Start 03-FEB-1992; Project End 31-AUG-2004 Summary: Our goal is to understand the functional significance and evolution of the polymorphism at the HLA-DP region and its relationship to disease susceptibility. Polymorphism at other HLA class II loci, DRB1 and DQB1 has been implicated for some time in predisposition to a variety of diseases. The role of the extensive polymorphism at the DPB1 locus (>80 alleles identified thus far) in disease predisposition is much less well understood. It is our hypothesis that specific combinations of alleles at multiple HLA loci determine the extent of susceptibility to a given disease. We will focus on three diseases: pauciarticular juvenile rheumatoid arthritis, type 1 diabetes, and cervical carcinoma. These diseases appear to have DPB1 associations as well as associations with specific alleles at the DRB1 and/or DQB1 locus. Our high resolution immobilized probe typing methods for the class II and class I loci will be applied to patient and control samples from a variety of populations. Family based material allows the analysis of haplotype sharing, transmission ratios, and linkage disequilibrium patterns as well as stratification analysis to see whether some of the associated alleles at DPB1, or any other individual HLA locus, confer increased risk or simply reflect linkage disequilibrium with high risk alleles at other HLA loci. Studying how HLA allelic diversity has evolved and how it is distributed in various human populations can provide insights into functional significance. The hypothesis that the patchwork patterns of polymorphism at the DPB1 and at other HLA loci reflects the operation of gene conversion (segmental exchange) will be tested by using a PCR-based method to measure the frequency of rare
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variant DPB1 sequences in sperm and the evolution of DPB1 diversity will be analyzed via phylogenetic analysis of exon2 and adjacent intron sequences from human and nonhuman primates. The hypothesis that HLA disease associations reflect the differential tendency to promote Th1 and Th2 responses following specific antigen stimulation of CD4+T cells will be examined using quantitative kinetic PCR to monitor cytokine expression. This method will be applied to HPV-infected cervical samples and an in vitro system with GAD peptide stimulation to study the HLA associations with cervical cancer and type 1 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HLA-DRB1 ALLELE SPECIFIC SIGNALING ABERRATION IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Holoshitz, Joseph; Associate Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001 Summary: The association of rheumatoid arthritis (RA) with particular HLA DRB1 alleles containing a shared epitope in their third allelic hypervariable region is well documented. However, how those MHC genes confer RA susceptibility is presently unknown. The currently leading hypothesis postulates that RA-associated alleles encode DRbeta chains, which may allow presentation of putative self-antigens. The identity of such arthritogenic antigens, however, remains unknown. The proposed research is offering a novel paradigm based on exciting preliminary data in the applicant's laboratory. According to that hypothesis, shared epitope-contining beta chains interfere with certain G protein-coupled receptor (GPCR) signaling events in a way that renders cells expressing them refractory to activation. This hypothesis is based on the observation that HLA-negative cells transfected with cDNA encoding shared epitopecontaining DRB1 alleles acquire the same signaling defects, which are found in cells of patients with RA and healthy individuals naturally expressing those DR genes. Furthermore, analysis of point-mutated cDNA transfectants demonstrates that the very same residues on the DRbeta chain, previously found to correlate best with RA susceptibility are essential for the observed aberration. Preliminary results suggest that the mechanism may involve GPCR desensitization. The goal of proposed research is to allow general examination of the role of G protein receptor kinases (GRKs) -mediated desensitization of GPCRs in the aberration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HSV GENE VECTORS FOR TREATMENT OF ARTHRITIS Principal Investigator & Institution: Glorioso, Joseph C. Professor and Chairman; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 20-APR-1997; Project End 31-MAR-2002 Summary: (Adapted from the applicant's abstract) - Rheumatoid arthritis is a chronic inflammatory disease affecting an estimated 10 million individuals in the United States alone. Currently, no effective long-term treatment other than joint replacement surgery is available. The overall aim of this proposal is to develop an in vivo gene therapy protocol for the treatment of arthritis. The first-generation gene therapy protocol using retroviral-mediated gene transduction demonstrated that antagonists of two cytokines, interleukin-l (IL-l) and tumor necrosis factor alpha (TNFa), can provide a significant therapeutic outcome in animal models of arthritis. These results are encouraging and
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provide the foundation of these proposed studies; however, it will never be practical to treat the millions of Americans who suffer from arthritis using an ex vivo strategy. Ex vivo treatments require sophisticated laboratories and protocols for transduction and selection of explanted cells. The goal of these studies is to develop an in vivo protocol in which gene transduction requires nothing more than an injection into the afflicted joint and thus, could become widely available in settings as simple as a physician's office. In vivo gene delivery will be accomplished with the injection of engineered Herpes simplex virus 1 (HSV1) vectors. HSV-l vectors have the advantages of high infectivity and the potential to express multiple transgenes. The major disadvantage of HSV vectors, their cytotoxicity, has largely been overcome by the deletion of the cytotoxic genes, ICP4, ICP22, ICP27, and UL41. These multiple deletion mutants are capable of replication only in complementing cell lines. They show greatly reduced cytotoxicity both in cell culture and in rabbit synovium with the acquired capacity for durable transgene expression in vivo. By using these replication-defective vectors, the principal investigator will be able to transduce synoviocytes in vivo to express antagonists of IL-l and TNFa, setting the stage for a simple and effective gene therapy treatment for arthritis. Four specific aims are proposed: 1) To construct HSV-l gene therapy vectors with further reduced cytotoxicity by deletion of the ICP0 gene; 2) to engineer HSV-1 vectors for coordinated expression of therapeutic genes; 3) to assess the effect of prior immunization with HSV on vector persistence and expression and to determine the effect of "antigenic stealthing" genes; 4) to assess the efficacy of HSV-l vectors for the direct in vivo gene therapy of the antigen-induced rabbit model of arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN LYMPHOCYTE ACTIVATION--ROLE OF DENDRITIC CELLS Principal Investigator & Institution: Steinman, Ralph M.; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2001 Summary: Dendritic cells are a trace subpopulation of white blood cells. When antigens are presented on dendritic cells to the immune system, strong immune responses are induced. Methods have been developed to isolate dendritic cells from human blood, inflamed joints and skin. We use dendritic cells to study different aspects of the immune response in transplantation, arthritis, psoriasis, and resistance to tumors and infectious disease (influenza, AIDS). Our aims include: a) Develop monoclonal antibodies and DNA probes to cell surface and intracellular constituents of dendritic cells. b) Outline the range of inflammatory cytokines and cytokine receptors that are made by dendritic cells from blood and from diseased tissues. c) Clone T cells that may mediate autoreactivity in rheumatoid arthritis and psoriasis, and protective immunity in tumors, influenza, and AIDS. d) Study the transmission of a cytopathic infection with the AIDS virus from dendritic cells that have been exposed to the virus (HIV-1) to CD4+ T cells. Compare dendritic cells isolated from blood, skin, and inflammatory sites. Test the effect of different types of immune T cells and anti-HIV antibodies on this transmission. Generate HIV-specific immune T cells of both CD4 and CD8 subsets. Evaluate the effects of immune T cells on HIV-infected monocytes. e) Develop methods for generating large numbers of dendritic cells from immature progenitors, and use these to present antigens from tumors and infectious agents (influenza, HIV-1) to human T cells. f) Evaluate mechanisms whereby dendritic cells present superantigens to T cells, including attempts to identify superantigens that may be carried by dendritic cells in autoimmune disease. g) Evaluate in human allogeneic bone marrow chimeras
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the ontogeny and kinetics of dendritic cell engraftment, the role of dendritic cells in immune reconstitution, and the identification of dendritic cell progenitors and conditions supporting their growth. h) Use dendritic cells to generate antigen-specific cytolytic T lymphocytes (CTLs) to viral, tumor, and auto antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN RETROVIRUS-5 AND ARTHRITIS Principal Investigator & Institution: Patel, Robin; Assistant Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Osteoarthritis and rheumatoid arthritis are the most common joint diseases of mankind. To date, no infectious agent has been convincingly associated with rheumatoid arthritis or osteoarthritis, although preliminary data ,suggest an association with human retrovirus-5, a newly identified retrovirus. That human retrovirus-5 is associated with both rheumatoid arthritis and osteoarthritis is, on initial consideration, striking, because these diseases are felt to be epidemiologically, clinically and pathologically distinct. However, it is possible that rheumatoid arthritis and osteoarthritis are both associated with human retrovirus-5, but that the immunologic response to the infection differs in each instance. The response may depend on the genetic background of the patient. Alternatively, genetic polymorphisms amongst human retrovirus-5 isolates may account for its association with two, seemingly unrelated, disease processes. The purpose of this proposal is to establish the association of human retrovirus-5 with rheumatoid arthritis and osteoarthritis, and to further characterize human retrovirus-5 by sequencing the entire viral genome and culturing the putative retrovirus. To achieve these goals, three specific aims are proposed. Specific Aim 1: Study the association of human retrovirus-5 with rheumatoid arthritis and osteoarthritis. Specific Aim 2: Sequence the entire viral genome of human retrovirus-5. Specific Aim 3: Culture human retrovirus-5. Intraoperative synovial tissue and whole blood specimens from 50 patients with rheumatoid arthritis and 50 patients with osteoarthritis, and synovial tissue specimens from 15 patients with normal joints will be collected and tested by nested polymerase chain reaction for human retrovirus-5 proviral DNA. Positive samples will be sequenced. The frequency of detection of human retrovirus-5 proviral DNA in synovial tissues and blood from rheumatoid arthritis and osteoarthritis patients will be compared to that in patients with no known joint disease. These samples will be used as sources of human retrovirus-5 in experiments to extend the known sequence of the human retrovirus-5 genome and culture the novel virus. Identification of a specific infectious agent associated with these arthritides would potentially allo for the development of preventive strategies such as vaccination and novel therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYALURONAN-MEDIATED NITRIC OXIDE PRODUCTION BY MACROPHAG Principal Investigator & Institution: Levesque, Marc C. Assistant Professor; Medicine; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 30-JUN-2002 Summary: Rheumatoid arthritis (RA) is a common disease that causes important suffering, disability and increased mortality, and represents an example of a chronic inflammatory immune response. RA is characterized by the overproduction of
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hyaluronan (HA) and production of low molecular weight HA oligosaccharides which have proinflammatory properties. Nitric oxide (NO) and TNFalpha are two important inflammatory mediators in RA. The mechanisms that induce NO production in human synovial macrophages and the downstream inflammatory effects of NO are poorly understood, especially in the context of diseases such as RA. Likewise, the mechanisms that perpetuate the continued production of TNFalpha in RA have not been completely characterized. This proposal will test the postulate that low molecular weight HA oligosaccharides perpetuate an inflammatory cycle of nitric oxide (NO) and TNFalpha production by synovial macrophages in RA, via the cell surface HA receptor CD44, that leads to further production of fragmented HA oligosaccharides. The specific aims are to: 1.) Compare the ability of HA oligosaccharides of different molecular weight to induce NO production by human monocytes and tissue macrophages. 2.) Determine whether HA oligosaccharides induce NO production by monocytes and synovial macrophages from patients with RA. 3.) Determine the ability of HA oligosaccharides to induce human macrophage cytokine production. 4.) Determine whether NO production by monocytes and synovial macrophages induces HA fragmentation. These studies will lead to future work that defines the molecular events involved in CD44 signaling and NO production by human macrophages and will also provide the rationale for therapeutic trials in RA patients that target inhibition of NO production and inhibition of CD44-HA interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF A GENDER-SPECIFIC RAT ARTHRITIS LOCUS Principal Investigator & Institution: Gulko, Percio S.; North Shore-Long Island Jewish Res Inst Jewish Research Institute Manhasset, NY 11030 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Collagen-induced arthritis (CIA) in rats is a wellestablished experimental animal model that has been used to gain insight into the pathogenesis of rheumatoid arthritis (RA), a chronic and commonly disabling disease with a prevalence of 1% in most populations. Both CIA and RA are complex trait diseases regulated by MHC and non-MHC genes, and both have an increased susceptibility among females, with a RA female to male ratio of 3:1. The factors that account for the increase female preponderance of RA are poorly understood. Gonadal hormones, particularly a reduction in their levels, have been implicated in disease pathogenesis, but that does not account for all the gender differences in disease expression. The underlying hypotheses of this proposal are that the non-MHC loci governing susceptibility and severity of CIA in rats will be highly relevant to the pathogenesis of RA, and also that at least part of the genetic susceptibility to CIA differs between females and males, with certain genes regulating disease in one gender but not in the other. The identification of these sex-specific genes, and the sex factors regulating their penetrance will be of great relevance to the understanding of the factors accounting for the increased female susceptibility, and could generate new targets for the development of more specific therapies, for prevention, diagnosis and prognosis. In a study of CIA in a F2 intercross between MHC identical inbred CIA-susceptible DA rats and CIA-resistant ACI rats, gender had a major effect in susceptibility and in arthritis severity. A genome-wide scan done separately for females and males led to the identification of a new non-MHC locus, Cia12, on chromosome 12, that regulates CIA in females, accounting for 24% of the genetic contribution to the variance in arthritis severity, but not in males. The rat Cia12 interval, and its syntenic regions in the mouse
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and human genomes contain loci regulating several forms of autoimmune diseases, including arthritis, suggesting that this gene may be relevant to different diseases, underscoring the broader relevance of this study. To identify this gene and to confirm and characterize its sex-specific effect a combined approach was planned. On Aim 1, speed-congenic lines will be generated, introducing the Cia12 interval from ACI rats into DA background, and vice-versa, and both genders will be studied separately for CIA. On Aim 2, gonadal hormones and neuro-endocrine manipulation are anticipated to determine the sex-specific mechanisms regulating Cia12. On Aim 3, sub- phenotypes involved in the autoimmune response, perhaps more directly regulated by Cia12 than the complex arthritic phenotype, will be identified and used in the narrowing of the interval of interest. This aim will also provide additional insight into the Cia12 gene function. On Aim 4 the specific gene will be identified based on candidate gene analysis or positional cloning, and disease-causing allelic variations characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDO: A NOVEL ENDOGENOUS SUPPRESSOR OF INFLAMMATION Principal Investigator & Institution: Varga, John M. Professor of Medicine; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2003 Summary: (Taken from the applicant's abstract): Rheumatoid arthritis (RA) is characterized by chronic progressive synovial inflammation and subsequent destruction of articular structures. The pathogenesis of rheumatoid synovitis involves complex interaction between T lymphocytes, autonomously activated fibroblast-like synovial cells (FLS) and networks of inflammatory cytokines. Activation of FLS with increased expression of matrix metalloproteinases (MMP) and cyclooxygenase-2 (Cox-2) enzymes are key steps in pannus formation and tissue invasion, and contribute to that catalyzes the initial and rate-limiting step in the metabolism of the essential amino acid tryptophan (TRP. IDO causes depletion of available TRP, culminating in local TRP starvation in tissue, and reduced TRP concentration in serum. IDO expression is induced by interferon-y (IFN-y) in multiple cells, including FLS. IDO activity is elevated in RA and other chronic inflammatory states, but the true physiologic role of this enzyme remains unknown. Recent observations from our laboratory and other investigators indicate that TRP depletion catalyzed by IDO exerts profound effects on immune and inflammatory pathways. We therefore now propose that IDO functions as a novel endogenous suppressor of inflammation, and modulates the course of inflammatory arthritis. Here we will examine the role of IDO in inflammatory arthritis in three interrelated Specific Aims. In Specific Aim 1, we will establish the fundamental importance of IDO and TRP catabolism in suppression of MMP and PGE production in normal FLS by IFN-y, and determine if constitutive IDO activation confers resistance of transfected cells to inflammatory stimuli in vitro. The cellular mechanisms underlying IDO-mediated suppression of inflammatory responses will be investigated in Specific Aim 2. In Specific Aim 3, we will examine if inhibition of IDO function in vivo murine collagen-induced arthritis using a competitive IDO inhibitor modulated the course of experimental arthritis. The potential of IDO and TRP starvation to modulate both early and late steps in the synovial inflammatory response makes an approach to synovitis treatment based on TRP depletion particularly appealing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IG-REACTIVE T CELLS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Salter, Russell D. Professor; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Between 70-80% of rheumatoid arthritis (RA) patients produce antibodies against IgG, called rheumatoid factors (RF), suggesting that IgG is a common auto-antigen in the disease. Although anti-IgG antibodies are present in other diseases and during immune responses to pathogens, these are generally low affinity IgMs that are detectable only transiently. In RA however, RF are persistent, usually of moderate to high affinity, and may include multiple isotypes. In addition, IgM RF can show evidence of somatic hypermutation. We therefore hypothesize that activation of T cells reactive with IgG could mediate affinity maturation and/or isotype switching in RF-producing B cells in at least a subset of RA patients. To address this, we have developed class II MHC tetramers containing peptides of Ig kappa chain that are shown to bind increased numbers of CD4+ T cells in some RA patients. In specific aim 1, we propose to determine how tetramer reactivity relates to expression of particular class II HLA proteins, including subtypes of HLA-DR4 shown previously to be associated with RA. In specific aim 2, we will test whether increased tetramer reactivity found in some patients correlates with the presence of multiple isotype rheumatoid factors, and with several markers, which can be used to measure disease severity. These experiments should critically assess the hypothesis that T cell help is required for production of multiple isotype RF, and may distinguish subsets of patients based on tetramer reactivity that have different prognoses, and who might benefit from distinct treatment regimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IL18 AND COMPLEMENT IN COLLAGEN INDUCED ARTHRITIS Principal Investigator & Institution: Arend, William P. Professor; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001 Summary: The long-term objectives of this project are to determine the roles of IL- 18 and the complement system in the induction of IL-1 and TNFalpha in collagen-induced arthritis (CIA) in mice and in rheumatoid synovial cells. IL-1 and TNFalpha are important mediators of tissue damage in rheumatoid arthritis (RA) and in CIA through stimulation of production of metalloproteinases in synovial fibroblasts and chondrocytes. The mechanisms of excess production of these cytokines in RA or CIA are probably multiple and largely unknown; IL-18 and the complement system are two potential inducers of IL1 and TNFalpha. The hypothesis to be examined in these studies is that inhibition of IL-18 with the specific IL-18 binding protein (IL-18BP), and of complement with the murine inhibitor, Crry, will attenuate the onset or ameliorate the course of CIA. This question will be addressed through three specific aims: 1) to examine the effects on CIA in mice of prevention of receptor binding of IL-18 with soluble IL-18BP; 2) to examine the effects of CIA in mice of blocking both the complement system and IL-18; and 3) to examine the relationship between production of IL-18, TNFalpha, and IL- 1beta in rheumatoid synovial tissue and cells. These experiments will utilize the administration of recombinant IL-18BP, the creation of mice transgenic for either, or both, proteins, and studies on isolated rheumatoid synovium tissue and cells. These studies are relevant to RA where IL-1 and TNFalpha are key mediators leading to inflammation and tissue destruction. The complement system and
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IL-18 may be important inducers of IL-1 and TNFalpha. These studies are further relevant to other autoimmune and inflammatory diseases where inhibition of injurious mechanisms at the proximal levels of complement and IL-18 may be efficacious. This research project will contribute towards the broad objective of the Autoimmunity Centers of Excellence program to study the mechanisms of new interventional approaches in both animal models of disease and in human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IL-18 IN RHEUMATOID INFLAMMATION AND ANGIOGENESIS Principal Investigator & Institution: Koch, Alisa E. Gallagher Research Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a prototype inflammatory disease characterized by leukocyte infiltration, which is in large part mediated by chemokines and cellular adhesion molecules. Angiogenesis, or new blood vessel growth, is integral to the development of the inflamed RA synovial tissue (ST) pannus. Without angiogenesis, leukocyte infiltration could not occur. A novel cytokine, interleukin (IL)-I8 has recently been identified. This cytokine stimulates T helper 1 (Thl) cytokine production by T cells. The functional role of this cytokine in RA is still unclear. In this proposal we hypothesize that IL-18 contributes to RA joint inflammation and angiogenesls. We plan to determine the mechanism by which IL-18 serves as an inducer of chemokine production in RA ST fibroblasts and whether this chemokine production occurs via G proteins, src family kinases, mitogen activated kinases, or PI3 kinases. Besides chemokines, cellular adhesion molecules are needed for leukocyte ingress into inflamed STs. We will examine whether IL-18 induces leukocyte-endothelial adhesion molecule expression and the mechanism of this expression. Finally, leukocyte ingress would not take place without angiogenesis. We will ascertain the mechanism by which IL-18 mediates angiogenesis in RA in terms of the endothelial signaling pathways, which are activated. Finally, we will study IL-18 gene-deficient mice to determine if they have impaired angiogenesis. We will employ these gene deficient animals bred on an arthritis-susceptible strain to examine whether arthritis associated angiogenesis in the joints is decreased. Several years ago cytokine modulation as a therapy for RA was simply a hope. Currently, cytokine modulation aimed at ablating tumor necrosis factoralpha is one of the best treatments available for RA and IL-1 targeting is beginning to be used therapeutically. IL-18, by virtue of its ability to induce chemokine release, adhesion molecule expression, and angiogenesis, appears to be a very critical cytokine to target. Our proposal should answer some key questions, which may determine the ability of IL18 to be a therapeutic target in RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNE DEVIATION INDUCED BY GENE VACCINATION-APPLICATIONS TO ARTHRITIS Principal Investigator & Institution: Corr, Mary P.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: Rheumatoid arthritis is a chronic inflammatory disease primary affecting peripheral synovial joints. The etiopathogenesis of rheumatoid arthritis appears to be multi-factorial, including hereditary susceptibility, postnatal events in immune
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maturation, repeated exposure to environmental antigens and amplifying cytokine networks that perpetuate inflammation. The causative antigens may be directly expressed at the site of immune attack pr be cross reactive with antigenic epitopes naturally occurring in the joint. We postulate that stimulating a subset of T cells that respond to a joint specific antigen to secrete IL4 or IL10 by manipulating the antigen presenting environment may abrogate disease. In our preliminary experiments we have developed a system whereby limited epitopes are expressed by plasmid DNA injected into the dermis or muscle tissues of mice. The T cell response to these antigens is additionally biased not only by the epitope expressed, but also by different costimulatory molecules expressed in the vicinity. This method of providing different elements involved in priming of an immune response creates a local immunologic window. In our laboratory we have also developed a unique system to limit antigen presentation to an isoform of CD1. We aim to 1) assess the effects of different costimulatory molecules on deviating the immune response to collagen 2) determine if providing additional antigenic chaperones or covalently linking the antigen chaperones potentiates immune deviation 3) evaluate a regulatory role for the CD1D1 restricted responses in collagen induced arthritis and 4) determine if the findings form our three strategies in the collagen induced arthritis model apply to a different transgenic mouse model in which the mice spontaneously develop arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOGENETICS OF COLLAGEN INDUCED ARTHRITIS IN MICE Principal Investigator & Institution: David, Chella S. Professor of Immunology; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-JAN-1983; Project End 28-FEB-2006 Summary: (provided by applicant): Collagen induced arthritis is an animal model for rheumatoid arthritis that shares a number of clinical, hematological, serological, and radiographic features with human disease. Type II collagen is a major component of articular hyalin cartilage and is a potential autoantigen in RA. Predisposition to RA has been linked to the MHC class II genes with haplotypes HLA-DQ8/DR4 showing the highest relative risk, and DQ6/DR2 being resistant. We generated transgenic mice expressing the above class II genes in the absence of endogenous class II molecules to generate a new humanized mouse model for rheumatoid arthritis restricted by human HLA class II molecules. Several interesting findings have emerged from our studies so far. In the current proposal, we will generate HLA-DQ transgenic mice expressing HLADQ4 and -DQ9 linked to RA in Asian and South American populations, and HLADR*O4O2 and *0404 which differ only in the HVR3 region residues to determine the role of the "shared epitope" in human RA. Double, triple, and quadruple transgenic mice will be generated to simulate human haplotypes to understand the interaction, gene complementation, and additive effect of multiple DQ/DR genes in the human disease. We will replace the mouse CD4 with human CD4 in these lines. Using knockout mice for CD4, CD8, and CD28, we will explore the role of costimulators in the disease process. We will identify the T cell and B cell specific epitopes on type II collagen, and look at the T cell repertoire and the TCR VB CDR3 usage. We will produce HLA class II tetramers in the context of human type II collagen peptides to identify specificity of collagen reactive T cells in the joints. Finally, using synthetic peptides and cyanogen bromide fragment of human type II collagen, we will explore various avenues of immunotherapy in the disease process. These studies should reveal the mechanism by which human HLA class II molecules predispose to human RA, and their role in the
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onset and severity of the disease. Thus, this humanized disease model for RA will have HLA class II, human CD4, and human type II collagen peptides as critical elements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOLOGIC BASIS ENIVR MODULATION OF AUTOIM ARTHRITIS Principal Investigator & Institution: Moudgil, Kamal D. Associate Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: (Taken from the Investigator's Abstract) Adjuvant arthritis (AA), inducible in susceptible rat strains by subcutaneous injection of heat-killed Mycobacterium tuberculosis H37Ra, serves as an excellent model for human rheumatoid arthritis (RA). Both arthritic rats and RA patients develop T cell responses to the 65-kilodalton (kDa) mycobacterial heat-shock protein (Bhsp65). Bhsp65 contains both arthritogenic and protective/regulatory T cell determinants. Heat-shock proteins (hsps) are highly conserved proteins both in prokaryotes and eukaryotes. The investigators have made an interesting observation that the susceptibility to AA of Fisher rats is very directly modulated by environmental agents: Fisher F344 rats bred and raised in a barrier facility (BB-Fisher) are susceptible to AA, whereas Fisher rats bred and maintained in a conventional (CV) facility (CVFisher) are resistant to AA. Furthermore, BB-Fisher rats, when transferred into a CV facility and kept there for several weeks, acquire resistance to AA. However, this acquisition of AA-resistance by BB-Fisher rats can be circumvented if rats are fed neomycin or acidified water (to prevent or diminish colonization of gut by environmental agents) beginning on the day of their transfer into the CV facility. Strikingly, naive CV-Fisher, and not BB- Fisher rats, spontaneously raised T cell responses to Bhsp65, including Bhsp65 C-terminal determinants (BCTD) [the investigators have previously shown that BCTD are involved in regulation of acute AA in the Lewis rat]. Furthermore, AA-resistance of CV-Fisher rats can be adoptively transferred to naive BB- Fisher rats by unfractionated splenic cells of naive CV-Fisher rats restimulated in vitro with BCTD. These preliminary findings provide a novel perspective on the role of microbes in autoimmunity: protection from an autoimmune disease instead of disease induction (the latter effect has been observed in several other animal models of autoimmunity). The investigators will test the following propositions in this exploratory study: A) Environmental agents are directly involved in conferring resistance against AA to CV-Fisher rats. Experimental reconstitution of BB-Fisher rats with microbial flora derived from CV-Fisher rats (for simplicity, these reconstituted rats are referred to as BBCV-Fisher rats) should render these rats resistant to AA. B) Microbial flora (containing hsp6O homologs of Bhsp65 of M. tuberculosis) induce protection from AA in CV- and BBCV-Fisher rats through an immunological mechanism. This hypothesis will be tested by priming T cells that are cross-reactive with Bhsp65 of M. tuberculosis (molecular mimicry). A subset of these T cells serves to afford protection from AA by mechanism(s) to be defined in this study. Alternatively, microbial flora may induce immune deviation of potentially arthritogenic T cells. C) The "acquired" AA-resistance of CV- or BBCV-Fisher rats should be adoptively transferable to naive BB-Fisher rats by a defined T cell subset (CD4/CD81). The results of this study should have important implications both for understanding the influence of environmental factors on the pathogenesis of RA in human populations living under different geographical conditions, and in developing new preventive/therapeutic approaches for RA.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOPROBES FOR LUBRICIN FROM HUMAN SYNOVIAL FLUID Principal Investigator & Institution: Jay, Gregory D. Associate Professor; Rhode Island Hospital (Providence, Ri) Providence, RI 02903 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Specific or related causes in the pathogenesis of osetoarthritis remain unclear despite a great deal of investigation. This justifies a new venue of research into other factors involved in degenerative joint disease. The study of joint lubrication, biotribology, has been fraught with conflicting theories, failure to adequately use molecular techniques, standardize merchanical assays and assign clinical importance to lubrication by synovial fluid. This investigation addresses the molecular of synovial lubrication of animal joints. A considerable literature has demonstrated that these rubbing and pressurized surfaces (i.e., bearings) have low frictional properties (1-4). These properties arise in part from the slippery nature of articular cartilage. Most reports actually deal with the rheology of synovial fluid and may incorrectly assume that its viscosity is the basis for joint lubrication (5-10). Direct measurements documents that synovial fluid lowers the coefficient of friction between cartilage bearings and certain artificial surfaces. A lubricating glycoprotein termed "lubricin" from synovial fluid is responsible for this but no one has proposed a mechanism of how it does so or how to study it in vitro. An arthrotripsometer composed of latex oscillating against glass employed by the PI reproduced critical findings of previous studies using cartilage bearings. It isolated boundary mode lubrication measuring devices previously employed by others. Synovial fluid, saliva, and detergents are the only substances which display this activity (11). The observation that lubricin lubricated the latex: glass bearing is a recent discovery by the PI. This provides an experimental opportunity to implicate failed lubrication in the occurrence of degenerative joint disease in a large number of patients and to causally link this measure to lubricin. A low coefficient of friction (mu) is no necessarily a measure of wear protection but synovial fluid does in fact confer this property to cartilage (12). It is unknown if the absence or paucity of lubricin is significant to the initial or continued pathogenesis of either osteoarthritis or rheumatoid arthritis. This principal goal of this investigation is to develop new immunological probes and with these identify the concentration of lubricin in synovial fluid extracted from healthy and arthritic human joints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INFLUENCE OF SEX AND HLA ON RHEUMATOID ARTHRITIS Principal Investigator & Institution: Moxley, George F. Associate Professor; Internal Medicine; Virginia Commonwealth University Richmond, VA 232980568 Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 30-JUN-2004 Summary: This application is to support a Midcareer Investigator Award allowing continued patient-oriented investigation into the genetic basis of rheumatoid arthritis (RA). The immediate goal is to examine how sex and HLA interact in RA heredity, while the long-term goal is to describe RA disease mechanisms in such detail that effective prevention or therapy will be possible. This award will provide career development support to protect time for this patient-oriented clinical research, develop new research skills, and do mentoring of junior investigators. The applicant will continue studies of sex influence on HLA penetrance in rheumatoid arthritis. The current studies have
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shown that RA is independently associated with several disease susceptibility loci in the HLA region, not just DRB1 variants but also independently with tumor necrosis factor (TNFalpha) variants. The future studies will define the functional correlates of TNF variants by identifying unrelated persons with common HLA genotypes and then examining inducible TNF production and MHC class II density in peripheral blood cells. Such results will be used to develop multivariate models to determine whether these explain sex differences in HLA penetrance. A second ongoing project, in cooperation with investigators at Case Western Reserve University, is to identify RA families suitable for genetic studies. A third project is proposed for this application. RA families will be studied to determine whether there is segregation distortion of RA-associated HLA haplotypes, that is, whether a child (either affected or not) is more likely than expected to inherit a RA-associated HLA haplotype from a mother with the HLA haplotype or a father with the HLA haplotype. Such parent-of-origin effects might represent genomic imprinting. Dr. Moxley has already demonstrated mentoring success, guiding junior investigators through design, performance, problem- solving, analysis, and publication. Virginia Commonwealth University has a rich patient population and strong programs to educate investigators in clinical research and biostatistics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION OF IL-6 AND STAT3 IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Ivashkiv, Lionel B. Associate Professor; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: Rheumatoid arthritis (RA) is a chronic inflammatory process that is characterized by the presence of activated monocytes/macrophages, T cells, B cells, plasma cells, and synovial fibroblasts in inflamed joints. Cytokines have been implicated in the activation of these cells and the pathogenesis of disease. Recent observations in a number of animal models of RA and in RA patients suggest that interleukin-6 (IL-6) plays a critical role in the pathogenesis have not been clarified, but potential mechanisms include activation of macrophages, stimulation of local antibody (rheumatoid factor) production, activation of T cells, and stimulation of myeloid and fibroblast differentiation into cells which directly degrade bone and cartilage. The activity of many cytokines, including IL-6, is mediated, in large part, by a major signal transduction pathway that utilizes Janus protein tyrosine kinases (Jaks) and STAT transcription factors. We have found that Stat3 is constitutively active in RA synovial fluid and tissues cells, that synovial fluids activate Stat3 in control cells, and that the major synovial fluid activator of Stat3 is IL-6. These observations have prompted an investigation of molecular mechanisms of inhibition of IL-6 signaling and Stat3 activation. One rapidly acting investigation of molecular mechanisms of inhibition of IL6 signaling and Stat3 activation. One rapidly acting inhibitory pathway that we have described involves the kinase cascade that activates the extracellular stimulus-regulated kinase (ERK) subfamily of mitogen activated protein kinases (hereafter termed the MEK-ERK pathway). This pathway inhibits signaling upstream of Stat3 activation and is relative specific for IL-6 and related cytokines that share the gp130 signaling subunit. We hypothesize that inhibition of IL-6 signaling is mediated by ERK kinase-dependent phosphorylation of the IL-6 receptor or an associated signaling molecule. We propose to delineate the molecular mechanism of inhibition and identify important regulatory molecules that can be targeted by novel therapies aimed at inhibiting cell activation during RA. Therefore, our specific aims are: (1) identify the IL-6 receptor sequences that mediate inhibition of signaling by the MEK-ERK pathway. (2) Determine the mechanism
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by which ERK-mediated post-translational modification of the IL-6 receptor or associated signaling molecules regulates the function of this receptor. (3) Characterize the functional consequences of ERK-mediated inhibition of IL-6 signal transduction using the M1 myeloid cell differentiation system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERLEUKIN-18 IN INFLAMMATION AND ANGIOGENESIS Principal Investigator & Institution: Park, Christy C. Medicine; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (Adapted from Applicant's Abstract) The study of cytokines is important to understanding inflammation and the immune system. Cytokines function to mediate normal physiologic processes, such as infection control and wound healing, but they can also regulate disease states such as autoimmune disease, rheumatoid arthritis (RA), or asthma. Interleukin (IL)-18 is a proinflammatory Cytokine, initially described as interferon-gamma- inducing factor. It is produced by activated macrophages, Kupffer cells, articular chondrocytes, osteoblasts, kerotinocytes, and synovial fibroblasts. IL-18 is structurally similar to IL-l beta and shares some of its biological actions, such as upregulation of the TH1 Cytokine and cell activation. Previous work has demonstrated its increased presence in RA and in an animal arthritis model. Preliminary evidence from our lab also supports a role for IL-18 in mediating angiogenesis, or new blood vessel growth, which is integral to the vasculoproliferation seen in RA as well as in would healing and tumorigenesis. IL-18 clearly contributes to the Cytokine cascade and maintains inflammation. However, the mechanisms by which IL-18 functions and its contributions to inflammatory disease processes need further investigation. The goal of the proposed research plan is to test our hypothesis that IL-18 contributes to the development of inflammation and angiogenesis in RA. The specific aims of the research are to determine: (I.) the cellular effects of IL-18 on stimulation of inflammatory mediators in RA synovial fibroblasts, which will be accomplished by determining whether IL-18 upregulates chemokines (chemotactic cytokines), arachidonic acid metabolites, degradative enzymes, and cell surface markers of inflammation; (II.) the action of IL-18 on an / inflammatory joint disease model, by employing mice deficient in the IL-18 gene, and examining the development of inflammation clinically and immunohistologically compared to normal mice; (III.) the angiogenic role of IL-18 in vitro and in vivo, by testing IL-18 in various bioassays for angiogenesis, including endothelial cell chemotaxis, proliferation, and tube formation, as well as blood vessel growth in vivo; (IV.) the action of IL-18 in mediating angiogenesis, employing in vivo angiogenesis and granuloma assays; (V.) the mechanisms by which IL-18 functions are regulated in a component of angiogenesis, namely endothelial cell migration. These research aims, if answered by the experimental methods above, will broaden our understanding of IL-18 functions and may ultimately direct the development of novel therapeutic targets against inflammatory and angiogenesis driven diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTRARTICULAR SLPI THERAPY FOR RHEUMATOID ARTHRITIS Principal Investigator & Institution: Labhasetwar, Vinod D. Associate Professor; Pharmaceutical Sciences; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2003
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Summary: (provided by applicant): Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by the loss of joint structure and function, resulting in significant pain and morbidity. In this proposal, we plan to investigate a new therapeutic strategy for the treatment of RA. In normal joints, the cartilage matrix turnover is maintained due to a balance between the activities of proteases and protease inhibitors. This balance is lost in arthritic joints, resulting in a greater protease activity, leading to cartilage and bone degeneration. Secretory leukocyte protease inhibitor (SLPI) has been identified as an endogenous potent protease inhibitor that maintains the critical balance against the proteases in the joint. Since SLPI is not produced by the joint tissue and the arthritic joints loose their ability to sequester SLP1 from the blood, it is hypothesized that intra articular administration of SLPI in a sustained release formulation would be effective in reinstating the balance between the proteases and protease inhibitors, and in inhibiting the progression of the disease. SLPI is also considered to be involved in protecting the cartilage growth factor (Link N) in the joint from protease-mediated degradation. The link N promotes the synthesis of proteoglycan and collagen, which are required for maintaining normal cartilage composition in the joint. Therefore, localized SLPI therapy could also lead to regeneration of the cartilage matrix and restoration of joint functions. Therefore, the objective of the proposed studies is to determine the efficacy of sustained intra articular delivery of SLPI using an injectable thermo reversible (TR) gel system in RA. The specific aims of the research program are: (1) To formulate a sustained release TR gel system for SLP1 using biodegradable and biocompatible Polyethylene oxide-Poly (L-Lactide)-Polyethylene oxide copolymer, and to evaluate the gel for sustained protein release properties, (2) To investigate the kinetics of intra articularly injected SLPI-gel system to provide localized and sustained delivery of the protein, and to determine the therapeutic efficacy of the gel to inhibit the progression of the disease in a rat streptococcal. cell wall-induced model of inflammatory erosive arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: JUVENILE RHEUMATOID ARTHRITIS: MRI ANALYSIS Principal Investigator & Institution: Dardzinski, Bernard; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: Juvenile rheumatoid arthritis (JRA) is the most common chronic inflammatory arthritis of childhood. The end result of ongoing synovial inflammation is degradation of articular cartilage. Whether the control of synovitis halts further cartilage degradation is not known. Irreversible thinning and erosion of cartilage leads to significant morbidity and loss of function. Magnetic resonance imaging (MRI) is proven to be a useful modality for depicting articular cartilage and synovium in both children and adults with inflammatory arthritis. Quantitative T2 mapping of articular cartilage in adults has shown that increased T2 relaxation time is an early marker of cartilage injury. This application will test the hypothesis that increased T2 relaxation time in articular cartilage of the knee in children with JRA reflects early cartilage injury. This quantitative method might possibly detect potentially reversible articular cartilage changes prior to irreversible cartilage erosions detected by conventional MRI. The longitudinal relationship between serial short-term changes in articular cartilage T2 relaxation time, degree of synovial inflammation, and clinical evaluation of disease activity will be determined. Articular cartilage T2 relaxation time in children with limited disease duration undergoing therapy will be quantified and monitored for reversibility. Serum and synovial fluid biomarkers will be measured and compared with alterations in
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articular cartilage T2 relaxation time. We will determine whether changes in T2 relaxation time profiles are predictive of articular cartilage erosions in children with JRA, and quantify and monitor reversibility of articular cartilage T2 relaxation time changes in children with longer disease duration. The long-term goal of this research is to provide a noninvasive, quantitative measure of early and potentially reversible degeneration in articular cartilage of children. These studies may extend the utility of MRI to quantitatively validate clinical outcomes in rheumatic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LEUKOCYTE MICROARRAYS IN JUVENILE RHEUMATOID ARTHRITIS Principal Investigator & Institution: Jarvis, James N. Associate Professor; Pediatrics; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, OK 73126 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Juvenile rheumatoid arthritis (JRA) is a family of illnesses characterized by chronic inflammation and hyperplasia of the synovial linings of joints. Its causes are unknown, and responses to treatment are often poor and associated with significant morbidity. Current theories of JRA pathogenesis have focused entirely on the role of T cells and adaptive immunity, failing to account for welldescribed abnormalities that implicate innate immunity in the disease process. We postulate that JRA pathogenesis involves complex interactions between innate and adaptive immunity. Traditional scientific approaches that focus narrowly and in depth on specific aspects of inflammation or immunity cannot grasp the complex pathogenesis at a single glance. DNA microarrays offer an ideal method for investigating these molecular interactions. Our preliminary experiments using DNA microarrays examined gene expression in peripheral blood buffy coat preparations from three children with polyarticular-onset JRA (poly-JRA). Our preliminary results indicate that the number of differentially expressed genes (compared to healthy age-matched controls) is 25-50 from an array of 2,400 genes. We now propose to continue to use buffy coat leukocyte preparations as the first step in identifying genes differentially expressed in additional children with active poly-JRA (Year 1). Once strong candidate genes have been identified, we will verify their expression and identify cellular localization in a single step using purified cell fractions (monocytes, granulocytes, and lymphocytes) and reverse transcriptase polymerase chain reaction (Year 2). We expect these pilot studies will provide the foundation for novel insights into the intersecting roles on innate and adaptive immunity in polyarticular JRA. Furthermore, these studies are likely to provide the basis for the elucidation of important prognostic markers and targets of novel therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LEUKOTRIENE B4 RECEPTORS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Bodduluri, Haribabu; Pathology and Lab Medicine; University of Louisville University of Louisville Louisville, KY 40292 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Neutrophils are found in large numbers in rheumatoid synovium and have been suggested to be involved in clinical signs of inflammation and pain associated with RA. Neutrophil activation during host defense and inflammation is
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mediated by G-protein coupled receptors (GPCRs) for chemoattractants. Leukotriene B4 (LTB4), a potent chemoattractant for neutrophils activates its receptor (BLT-1) to mediate diverse physiological effects in neutrophils. A second LTB4 receptor (BLT-2) with distinct antagonist specificity and tissue distribution was recently described. GPCRs are regulated by receptor phosphorylation leading to desensitization as well as down regulation. We will test the hypothesis that LTB4 acting through the high affinity receptor BLT-1 mediates its effects on neutrophils in RA, while LTB4 acting through BLT-2 modulates T-lymphocyte activation and function in RA. The goal of the current studies is to develop comprehensive in vivo and in vitro models to determine the role of LTB4 and the relative contributions of BLT-1 and BLT-2 in the development of murine RA. In specific aim 1 we will define the role of BLT-1 in the development and progression of collagen induced arthritis in the BLT-1 deficient mice we have already generated by targeted gene disruption. In specific aim 2 we will use the well-established RBL-2H3 cell model to determine the differences in signaling, desensitization, internalization and antagonist specificity of BLT-1 and BLT-2. These studies take advantage of the novel video microscopy and live cell imaging methods we have recently developed. Leukotrienes are involved in the pathophysiology of many acute and chronic inflammatory diseases such as systemic anaphylaxis, atherosclerosis, RA and asthma. Understanding the precise function of distinct LTB4 receptors in mice deficient in specific receptors and defining the role of these receptors in RA will identify novel targets for therapeutic intervention of RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARTHRITIS
LMP
POLYMORPHISMS
IN
B27-ASSOCIATED
JUVENILE
Principal Investigator & Institution: Colbert, Robert A. Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2001; Project Start 20-AUG-1997; Project End 31-JUL-2002 Summary: Juvenile rheumatoid arthritis (JRA) is a heterogeneous autoimmune disease likely to result from multiple genetic and environmental factors. One genetic factor encoded in the class I region of the major histocompatibility complex (MHC), and associated with late onset particular JRA, is HLA-B27. In preliminary studies we have identified homozygosity for the B allele of LMP2, one of two MHC-encoded proteasome subunit genes (LMP2 and LMP7), as an additional genetic risk factor for susceptibility to arthritis in HLA-B27-positive children. Since proteasomes ar involved in the generation of peptides presented by MHC class 1 molecules like B27, we hypothesize that polymorphisms in LMP7 may also affect susceptibility to JRA. Furthermore, LMP2, LMP7, and their allelic variants may influence the production of peptide epitopes presented by HLA-B27, thus influencing disease susceptibility in these individuals. This proposal outlines a career development program designed to complete the training of a physician-scientist interested in the molecular mechanisms of HLA-B27-associated autoimmune disease pathogenesis. It relies on the strengths and potential of a Howard Hughes Medical Institute research laboratory headed by Dr. John Monaco to provide further training in modern techniques of molecular immunology, particularly with regard to proteasome function, and strong Division of Rheumatology headed by Dr. David Glass, with long-term interests and expertise in genetic associations in JRA. In addition to the basic research component, the training program will provide the candidate an expanded knowledge base in immunology through participation in lab meetings, journal clubs, and research seminars. In Specific Aim 1 we propose to use molecular genotyping to confirm and extend our initial observations wit LMP2, and
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determine whether LMP7 polymorphisms are associated with subgroups of JRA. In Specific Aim 2 we address the role of LMP subunits in influencing the cleavage site specificity of proteasomes by digesting oligopeptides containing known HLA class Irestricted peptide epitopes. Epitopes will be identified and their relative quantities assessed, using mass spectroscopy (MS) and cytotoxic T lymphocyte (CTL) assays. In Specific Aim 3 we will test hypothesis that LMP2 and LMP7 polymorphisms result in functional differences in proteasome activity. In vitro mutagenesis will be used to mimic naturally-occurring polymorphisms in LMP2 and LMP7, and cleavage site specificity of proteasomes containing these allelic variants will be assessed using MS and CTL recognition assays. These studies will define the association between LMP alleles and JRA, and contribute to our understanding of the function of MHC-encoded proteasome subunits and the significance of their allelic variation. Furthermore, they will essential to our determining how polymorphic gene products involved at different sites in the class I antigen processing pathway might interact to predispose certain individuals to JRA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LUBRICIN FUNCTION IN ARTICULATING JOINTS Principal Investigator & Institution: Warman, Matthew L. Assistant Professor; Genetics; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The integrity of the cartilage surface and its surrounding synovium affects the homeostasis and long-term function of an articulating joint. The loss of superficial zone chondrocytes and fibrillation of the cartilage surface are early signs of osteoarthritis. Intimal cell hyperplasia and sub-intimal fibrosis is striking in rheumatoid arthritis where joint destruction is, in part, mediated by aggressive and invasive synovial overgrowth. This application proposes to explore the role of the secreted protein lubricin (also known as megakaryocyte stimulating factor precursor, superficial zone protein, camptodactyly-arthropathy-coxa vara-pericarditis syndrome protein, and proteoglycan 4) in the maintenance of articulating joints. This protein has several important roles in joint homeostasis, including the protection and boundary lubrication of articulating surfaces, and the regulation of intimal cell growth. Genetic deficiency of this protein causes the autosomal recessive CACP syndrome, which is associated with precocious joint failure, and acquired deficiency of this protein likely contributes to joint failure in osteoarthritis and rheumatoid arthritis. Since lubricin is a protein that is synthesized by surface chondrocytes and synviocytes and is secreted into the synovial fluid, we speculate that it may be a useful agent, or target, in the treatment of common joint disease. This application has four major aims: Aim 1) Characterize the lubricin knockout mouse with respect to cell biological properties of synoviocytes, and the biophysical and structural properties of the articular surface (lamina splendens). Aim 2) Delineate which domains in lubricin are important for its post-translational modification and biologic properties, such as protein-protein interactions, lubrication, and cell growth regulation. Aim 3) Create a transgenic mouse in which lubricin expression can be exogenously regulated. This will allow us to explore the temporal role of lubricin in joint development and homeostasis. Aim 4) Identify hereditary and acquired alterations of lubricin function within synovial fluid from patients with CACP syndrome and common diseases of joints including osteoarthritis, rheumatoid arthritis, and traumatic joint injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF INDUCED PROTECTIVE IMMUNITY IN MURINE CIA Principal Investigator & Institution: Haqqi, Tariq M. Associate Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 30-JUN-2003 Summary: Type-II collagen induced arthritis in mice (CIA) is a well studied animal model of inflammatory polyarthritis with many similarities to human rheumatoid arthritis (RA). In this model arthritis is induced in susceptible strains of mice and rats after immunization with hetrologous or autologous type-II collagen in complete Freund's adjuvant and the induction of arthritis is MHC restricted. In previous studies performed by our laboratory we identified a new CIA susceptible strain, BUB/BnJ (H2q, TCR Vba), and showed that induction of arthritis in BUB mice is associated with a restricted use T cell antigen receptor (TCR) variable region genes (Vbeta) in the arthritic joints and was limited to TCR Vbeta3 and Vbeta10 genes. Most recently we demonstrated that mice preimmunized either with a mixture of TCR Vbeta3 and Vbeta10 peptides or with TCR Vbeta10 peptide alone were highly protected against the induction of CIA upon subsequent challenge with chicken type-II collagen (C-II) in CFA. The experiments in this proposal focus on further characterizing and understanding the mechanism of this protective immune response. The fundamental hypothesis of this proposal is that protective immunization induces an anti-Vbeta10 peptide immune response characterized by IFN-gamma producing T cells and IgG2a subtype antibodies (Th1 immune response) and this immune response subsequently results in the elimination or downregulation of the arthritogenic immune response. In order to perform these studies we have developed a highly sensitive ELISA spot assay capable of detecting cytokine production by single T cells, and have used this assay to show that (1) we can preferentially induce either a Th1 type or Th2 type anti-Vbeta10 immunity in vivo by simply altering the immunization protocol; (2) arthritis protected mice had antiVbeta10 specific CD4+ T cells which produced IFN-gamma while arthritic mice had IL-4 producing T cells. We will now fully characterize the recall Th1 or Th2 immune responses after immunization with Vbeta10P using the ELISA spot assay, standard cytokine ELISA and RT-PCR for cytokine message and TCR Vbeta gene usage. We will then determine how the induced anti-Vbeta10 immune response affects the quantity and cytokine profile of pathogenic immunity directed towards type-II collagen and towards a newly identified immunodominant determinant in BUB mice derived from typecollagen. Finally we will study how passive transfer of Vbeta10 specific antibodies and T cells affects the clinical expression of CIA as well as how it affects the pathogenic immune response directed at type-II collagen. The results obtained are expected to provide novel insight into the mechanisms of induced protective immune responses that may be relevant to the treatment of human rehumatoid arthritis and other autoimmune disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF ANTIFOLATE EFFICACY Principal Investigator & Institution: Morgan, Sarah L.; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001 Summary: Low-dose methortrexate therapy suppresses autoimmune arthritis in human and animal models. It is our hypothesis that the effect of methotrexate in the treatment of rheumatoid arthritis is due to the inhibition of aminoimidazole-carboxamide ribotide
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transformylase, a folate-dependent enzyme which catalyzes the last step in the de novo biosynthesis of inosine monophosphate. The resulting accumulation of aminoimidazole carboxamide riboside inhibits adenosine deaminase, therefore, interfering with normal adenosine metabolism. It is well known that children with adenosine deaminase deficiency have severe-combined-immunodeficiency syndrome. This suggests that adenosine deaminase activity is key to immune competence and is associated with the mechanism of efficacy in methotrexate therapy of rheumatoid arthritis. Several studies indicate that supplemental folinic acid (5- formytetrahydrofolate) used in large doses during low-dose methortrexate therapy for rheumatoid arthritis causes a flare in joint inflammation. However, supplemental folic acid (pteroylglutamic acid) does not lessen the efficacy of the therapy. We further hypothesize that if methotrexate efficacy is driven by aminoimidazole carboxamide ribotide transformylase inhibition, folic acid supplementation should not alter urinary levels of aminoimidazole carboxamide, adenosine, and deoxyadenosine, while folinic acid supplementation should prevent the accumulation of these compounds. Our hypotheses will be tested both in patients with rheumatoid arthritis and in Lewis rat adjuvant arthritis. Objectives include A) to determine whether supplemental folic acid and folinic acid during methotrexate therapy normalize adenosine metabolism in patients with rheumatoid arthritis. The information obtained from the proposed research will enhance the understanding of the biochemical action of antifolates/ antimetabolites that are effective in the treatment of human and animal arthritis. To date, six patients have been enrolled in the trial. Because the trial is blinded, no data is yet available. It is planned inthe upcoming year to enroll patients, up to a total of 50 patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF MYCOPLASMA-INDUCED ARTHRITIS Principal Investigator & Institution: Dybvig, Kevin F. Genomics and Pathobiology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: ( applicant's abstract): Mycoplasma arthritidis causes a naturally-occurring, migratory polyarthritis in rodents that bears a close histological resemblance to rheumatoid arthritis of humans. M. arthritidis-induced arthritis has been extensively studied as a model for arthritides caused by infectious agents and also as a model for examining the role(s) of superantigens in the development of autoimmunity. All strains of M. arthritidis are thought to produce the superantigen MAM, but many an MAM must be required for the development of arthritis. One of these factors is the lysogenic bacteriophage MAV1. Avirulent strains of M. arthritidis become virulent when lysogenized with MAV1. MAV1 DNA integrates into the M. arthritidis chromosome at any of numerous sites, and the site of integration does not correlate with virulence. Therefore, the increase in virulence associated with MAV1 does not result from changes in regulation of chromosomal genes flanking MAV1 DNA inserts. We have proposed that MAV1 encodes a determinant that is involved with the development of arthritis. MAV1 is the first factor from any mycoplasma that has been shown to be associated with arthritis, and elucidation of this factor is important for fulfillment of the long-range goals of understanding the mechanisms of mycoplasma-induced arthritis and the role of phages as carriers of bacterial arthritogenic determinants. Factors analogous to the MAV1-encoded determinant may be prevalent in bacteria and mycoplasmas that cause arthritis in humans, and these factors may be important as vaccine candidates and as targets for drug design. The goals of the present application are to identify and characterize the MAV1-encoded determinant and initiate studies to elucidate its
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function. From the nucleotide sequence of the 16-kb MAV1 genome, we have identified a candidate virulence determinant that is predicted to encode a membrane lipoprotein. Specific Aim 1 is to conclusively identify the particular MAV1 gene(s) associated with virulence of M. arthritidis. Specific Aim 2 is to determine whether the MAV1 virulence factor is a cytoplasmic or membrane protein and is produced in vivo. Specific Aim 3 is to explore the role of MAV1 in disease pathogenesis. How lysogenization of M. arthritidis by MAV1 affects the progression of arthritic disease will be examined. Through the use of immunocompromised animals, we will address the question of whether MAV1 contributes to the virulence of M. arthritidis by affecting interactions with host factors such as B and T cells and complement. Thus, the process of dissecting the function of MAV1 in virulence will be begun. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF RHEUMATOID SYNOVIAL FIBROBLAST ACTIVATION Principal Investigator & Institution: Bucala, Richard J. Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2002; Project Start 21-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Rheumatoid arthritis causes significant disability and mortality. The joint capsule or synovium undergoes profound phenotypic changes during this disease, resulting in the hyperplastic and invasive tissue known as rheumatoid pannus. Pannus leads to cartilage and bone destruction, and the synovial fibroblasts within pannus show a persistently activated state characterized by increased proliferation, decreased apoptosis, and sustained growth factor and matrix-degrading enzyme secretion. Precisely how these phenotypic changes are initiated and become perpetuated in synovial fibroblasts is not understood, and this lack of knowledge is an important problem because without this information, more selective approaches to the treatment of arthritis cannot be undertaken. Our long-range goal is to understand the pathogenesis of rheumatoid pannus. The objective of this application is to understand the mechanisms underlying the persistent activation of synovial fibroblasts. The central hypothesis is that the cytokine, macrophage migration inhibitory factor (MIF), induces sustained ERK-1/2 activation, invasive phenotype, and suppression of p53-dependent apoptosis in synovial fibroblasts. We have formulated this hypothesis on the basis of our discoveries showing that immunoneutralization of MIF prevents arthritis development in murine models, and that MIF induces a sustained pattern of activation of the ERK-l/2 MAP kinase cascade in the well-defined, NIH-3T3 cell line. MIF also has been shown to uniquely inhibit p53-dependent apoptosis. The rationale for this research is that once it is known how persistent pathways of cell activation become induced in synovial fibroblasts, new approaches for intervention in joint destruction may be devised. We will test our hypothesis and accomplish the objective of this application by pursuing the following two specific aims: 1) Define the Pathways by which MIF Activates Synovial Fibroblasts, and 2) Determine MIF's Role and Mechanism of Action in the Inhibition of p53-dependent Apoptosis. The proposed work is innovative because it capitalizes on two recently discovered and potentially unifying mechanisms, sustained ERK-1/2 activation and p53 functional inactivation, to explain the hyperplastic and invasive phenotype of rheumatoid pannus. It is our expectation that this work will define the molecular basis for the sustained pro-proliferative and invasive phenotype of rheumatoid synovial fibroblasts. These results will be significant because they will provide a precise understanding of the molecular pathways responsible for the erosive
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properties of synovial pannus and ultimately facilitate the development of new and selective strategies for the treatment of rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROARRAY ANALYSIS--SYNOVIAL GENE EXPRESSION IN ARTHRIT Principal Investigator & Institution: Brahn, Ernest; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001 Summary: An analysis of the expression/regulation of specific genes in the synovium is critical to an understanding of the events that initiate and propagate chronic inflammatory synovitis in collagen-induced arthritis (CIA) and rheumatoid arthritis. Microarray technology represents a high-throughput approach to study and statistically compare numerous genes The LOU rat CIA system has several advantages over human autoimmune systems since it uses syngeneic rats, can be reproducibly studied at any time point in arthritis development, and allows the capacity to simultaneously harvest control tissue as well as the end organ of interest, the synovium. Because of limitations in microarray quantitation, RT-PCR will be needed for confirmation only of the selected genes that have altered expression. This analysis could define which gene products might be important at each stage of disease and could provide targets for fixture therapeutic interventions. Since not all LOU rats (even though they are syngeneic) develop CIA following immunization with collagen, early differences in gene expression, compared to their arthritic littermates, might explain this observation. Specifically targeted therapeutic interventions, such as sTNF-Rl, IL-lra, or p38 MAP kinase inhibitors, can be evaluated by microarray methods in the CIA system (and potentially in RA) to clarify their proximate (e.g. TNF, TNF-R2, IL-1) and subsequent (e.g. metalloproteinase) effects on synovial gene expression. This could result in a better understanding of the in vivo mechanisms of how these agents work (in rats with arthritis regression) or don't work (in rats with arthritis progression). An initial pilot study with normal LOU rat spleen/lymph node/liver (non-lymphoid control)/synovial tissue will define optimal procedures and conditions for rat microarray methodology. This utilizes tissue that is readily available and establishes a naive background level of gene expression for later comparison. Most of the previous studies on gene expression profiles in arthritis utilized a small panel of genes encoding potentially proinflammatory molecules. In contrast, the microarray includes, in addition, genes that encode molecules responsible for anti-inflammatory effects, metallo-proteinases, bmps, differentiation antigens and factors, transcription factors, and signaling molecules. All of these can help to reveal the on-going pathology and also become targets of therapy in the future. After induction of CIA on day 0, synovial and control tissue from rats will be harvested during the course of arthritis development (day 7-subclinical disease, day 10clinically evident arthritis onset, day 17-established arthritis, day 28-late arthritis). Microarray analysis will provide sequential data on gene expression as it relates to arthritis progression. Candidate genes will be confirmed by RT-PCR. By testing a number of individual rats, a common gene expression profile at each time point will be generated. Subsequent studies will analyze the effects of specific biologic interventions with sTNF-RI , IL-Ira, p38 MAP kinase inhibitors as single agent or combination interventions in rats with early (day 10) CIA. Patterns of gene expression will be compared with the typical expression defined in naive and CIA control rats at day l7 and day 28. If a therapeutic agent does not alter the gene expression profile, it would indicate that the agent is blocking certain final mediators of the disease. If a therapeutic
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agent alters the gene expression profile drastically, the changes in the downstream molecules are then responsible for the clinical improvement. This is especially useful when testing therapeutic agents that block signaling pathways. These investigations should identify direct and subsequent effects on gene expression using protocols that selectively target an inflammatory element that has already shown potential utility in rheumatoid arthritis therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF HUMAN VH GENE REPLACEMENT Principal Investigator & Institution: Zhang, Zhixin; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: provided by applicant): The candidate is a molecular biologist who wishes to establish an independent research career in the molecular immunology field. Enhanced training under Dr. Max D. Cooper?s supervision in immunology is proposed for the initial two or three years in order to achieve research independence within the award period. The proposal will focus on the molecular basis and regulatory mechanism of human VH gene replacement and its contribution to normal B cell development, B cell responses, and rheumatoid arthritis in particular. The hypothesis builds on an analysis of a clonal human cell line, EU12, that undergoes continuous in vitro differentiation from proB (CD34+) to preB (CD34 mu SLC+) then to B cells (CD34 mu+LC) and generates intraclonal diversity through serial VH replacements. The ongoing VH replacement in the EU12 cells is verified by the detection of VH replacement excision circles and double stranded DNA breaks at the cryptic RSS sites. (Aim 1) The EU12 cells will be used as an experimental model to dissect the molecular basis for the VH replacement. Purified RAG 1, RAG 2, and HMG 1 proteins will be used in in vitro studies to define the function of the cryptic RSS site. (Aim 2) Using the methods and principles derived from the study of the EU 12 model, normal human bone marrow and tonsillar germinal center B lineage cells will be used to investigate the occurrence and stage(s) of VH replacement in humans. (Aim 3) The regulatory mechanism of VH replacement will be investigated using the EU12 model through evaluating the effects of. (i) modulating surrogate light chain (lamda 5/14. 1) or conventional light chain (kappa and lamdaX) expression, (iii) ligating cell surface receptors (pre BCR, BCR, and CD40), and (iii) stimulating with cytokines (IL 1 beta, TFNaphla, IL 6, and IL 7) on VH replacement. (Aim 4) Determine if VH replacement occurs in synovial B cells thereby contributing to the generation of autoantibodies and to search for potential VH replacement stimuli in rheumatoid arthritis synovial tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MODELING OF MHC II-PEPTIDE ISOMERS Principal Investigator & Institution: Belmares, Michael P. Chemistry; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 30-NOV-2000 Summary: The molecular level modeling of MHC II-peptide systems to obtain a solid theory of the origins of autoimmune systems, particularly rheumatoid arthritis (RA) is proposed. The first modeling efforts will be directed toward a systematic search of the structure of a "kinetic" isomer of an MHC-peptide system where a long and a short lived isomer have been observed (MHC II I-E/kPiggeon Cyt c peptide). Then, a hypothesis has been laid out in the proposal where a specific kinetic isomer of a collagen peptide in
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HLA-DR4 (DRB1 0401 allele) is not recognized as "self" by the immune system. The Tcells recognizing the "kinetic" isomer may not have been eliminated during the early maturation stage. Modeling of the proposed isomer will be done and may be eventually confirmed through experimental techniques at the McConnell lab. Specifically, it is proposed that water molecules solvating the two carboxylates in the P6 pocket of HLADR4 may interfere with the deep burial of the P6 Ala of the collagen peptide observed in the MHC-peptide crystal structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR THERAPEUTICS OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Carson, Dennis A. Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 28-SEP-1998; Project End 31-AUG-2003 Summary: Current concepts of rheumatoid arthritis (RA) pathogenesis indicate that the disease is not caused by a single genetic defect, infection, or autoimmune reaction, but rather by improper control of host immune, inflammatory, and proliferative responses within the joints. This revised application for a Specialized Center for Research (SCOR) in RA focuses on this central theme. It contains four projects. Each concerns a molecular defect that may contribute to immune dysregulation and pannus formation in RA. Furthermore, each project aims to develop a therapeutic strategy to correct how bacterial and host-derived immunostimulatory DNA sequences can induce normal T1-type immune responses within the joints, and will demonstrate how ISS action might be interrupted therapeutically. Project 2: "The Synovium as an Immune Underprivileged Site" (Thomas J. Kipps, M.D. PhD. Project Leader) aims to delineate how the proteolytic environment within the joint prevents deletion of activated immune cells, and will devise gene therapeutic strategies to correct the defect. Project 3 "Immune Deviation Induced by Gene Vaccination: Applications to Arthritis" (Mary P. Corr, M.D. Project Leader) aims to deviate pro-inflammatory Th1 immune responses toward a less inflammatory Th2 phenotype by the creation of an "immunologic window" through genetic engineering of DNA vaccines. Project 4: "Properties of Shared Epitope-Specific T Cells in RA" (Salvatore Albani. M.D. Project Leader will discriminate the functional properties of isolated T cells from RA patients that recognize the shared epitope and will explore how pharmacological invention can change their frequency or function. The four projects will be supported by an Administrative Core (Dennis A. Carson, M.D. Director), that will coordinate the research and monitor its progress, and by a centralized Research Resources Core (Gary S. Firestein, M.D. Director), that will collect and distribute patient samples, and provide assistance with the evaluation of animal models. When completed, the experiments proposed in the SCOR will demonstrate how specific molecular abnormalities can promote the development of chronic arthritis, and will describe specific approaches for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTIDISCIPLINARY CLINICAL RESEARCH CENTER AT BOSTON U Principal Investigator & Institution: Felson, David T. Professor and Chair; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: OF THE OVERALL PROGRAM: (Taken from the application): This proposal represents a competitive renewal of the Boston University Multipurpose Arthritis and
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Musculoskeletal Diseases Center grant which was established in 1977 and built on a strong foundation of outstanding epidemiology and health services research along with basic biomedical research. We have parlayed this excellence in epidemiology and health services research into a Multidisciplinary Clinical Research Center (MCRC) application. The strong record of accomplishment in patient oriented medical research at Boston University has been not only maintained in the last four years but expanded. What we propose creates new directions and areas of research for this already productive group of investigators who work together closely, and it promises to produce further major insights into rheumatic disease causation and treatment. Led by Director, Dr. David Felson and Associate Director, Dr. Timothy McAlindon, this group of full time MCRC investigators who work together in shared office space will meet weekly in Methodology Core group meetings to discuss and review both projects proposed here and other funded and nonfunded clinical research. This Core will provide support for the four proposed projects: Project 1: A Randomized Trial of a Wedged Insole for Treatment of Osteoarthritis of the Knee, David T. Felson, PI; Project 2: Can Case-Control Studies Of Rare Diseases Be Performed Over The Internet, Timothy McAlindon, PI; Project 3: Work Disability: How are Persons with Rheumatoid Arthritis Currently Faring?, Saralynn Allaire, PI; and Project 4: Correlates of Articular Cartilage thickness in knees of subjects from the Framingham Study, David T. Felson, PI. An administrative unit will provide oversight to ensure that these projects are successfully accomplished and that core resources for support of these and other projects are allocated efficiently. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIPURPOSE ARTHRITIS & MUSCULOSKELETAL DISEASES CENTER Principal Investigator & Institution: Hahn, Bevra H. Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 15-JUL-1987; Project End 30-JUN-2003 Summary: The revised proposal from the UCLA MAMDC builds upon our prior work in the basic science of autoimmunity, and in defining and modifying some factors that impact on outcome in patients with rheumatoid arthritis (RA). Twenty- five investigators are participating directly in the proposed projects and core units; many more as expected to use the core to enrich their scientific endeavors. The proposal offers 4 development and feasibility (D&F) studies, all designed to develop the career of a beginning faculty- level investigator, and a biomedical core unit for peptide synthesis. The D&F studies will explore the role of CD1-restricted T cells in host defense against staphylococci, both in normal people and in patients with septic arthritis; 3) the influence of loading MHC Class I and II molecules with T-cell stimulatory peptides via administration of mini-genes on the T cell functions that influence autoantibody formation in murine lupus, and 4) the importance of a chromosome region near the beta2-glycoprotein I locus on ability to make antibodies to cardiolipin, and the influence of those antibodies on lipoprotein metabolism in autoimmune mice with accelerated coronary artery disease. In the education, epidemiology and health services research (EESHR) portion of the proposal, we aim to establish methods for assessing quality of care in patients with new onset RA, assuming that appropriate interventions in this cohort influence outcomes. A core unit and two projects will focus on developing valid methods to measure care as a function of structure (patient demographics and characteristics of the health unit administering care), process (the interventions that happen to patients such as physician visits), and outcome (physical, socioeconomic, administering care), process (the interventions that happen to patients such as physician
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units), and outcome (physical, socioeconomic, psychological characteristics of patients from entry to two years later). The core will develop and validate measuring instruments, train data collectors, collect and clean data, and provide advise regarding data analysis. In one project (Claims Data), claims data on 400 patients with new onset RA from a large managed care organization will be analyzed and validity compared to information obtained from chart review and patient self-report. In the second project (Practice Patterns), information will be obtained from chart review and patient selfreport from 400 patients with new onset RA receiving care at VA Medical Centers, Kaiser Permanente, and Mullikin MedPartners. The purposes of this HSR component is to establish valid measures of quality of care in RA, based on structure process and outcomes. Each project will identify and enter patients, supervise the scientific aspects of data collection and management, and analyze the data. The MAMDC efforts will be supervised and coordinated by an administrative unit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIPURPOSE ARTHRITIS & MUSCULOSKELETAL DISEASES CENTER Principal Investigator & Institution: Winfield, John B. Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-1982; Project End 30-JUN-2003 Summary: The Multipurpose Arthritis & Musculoskeletal Diseases Center at the University of North Carolina at Chapel H. chartered by the School of Medicine as the Thurston Arthritis Research Center, consists of a Biomedical Research Component, an Education, Epidemiology, & Health Services Research (E/E/HSR) Component, a Biomolecular Core, a Numerical Sciences Core, and an Administrative Unit. Ongoing and planned investigation in the Biomedical Research component encompasses many of the issues relevant to autoimmunity, arthritis, and musculoskeletal disease: genetics, regulation, and function of recognition elements in normal and abnormal immune responses; peptide/MHC structure function relationships; induction and regulation of cytokine and inflammatory responses genes; the repertoire of T cell receptor and B cell Ig genes and their role in autoimmunity; T cell activation and signal transduction; molecular genetics of autoantibody formation; contribution of autoantibodies to disease pathogenesis; immunosuppression; inciting agents in autoimmunity; inflammation in experimental arthritis and its therapy; biochemistry and cell biology of cartilage; pathophysiology of mechanical joint injury and its relationship to osteoarthritis; clinical investigation of arthritis, osteoporosis, and systemic connective tissue diseases; and mechanisms of pain. Three Development & Feasibility projects are proposed. "Mechanisms of anti-nRNP/Sm autoantibody spreading"; "The role of beta2GPI in apoptosis"; and "Prevention of Arthritis with Dietary Glycine". A Biomolecular Core provides: serological and clinical databases and a cell bank; flow cytometry; and inbred mouse colony; and a biomolecular imaging facility. Research themes in the E/E/HSR Component include: 1) studies aimed at increasing our understanding of how people adapt to and cope with arthritis; 2) development or validation of measurement procedures related to arthritis; 3) epidemiological studies aimed at describing the prevalence, correlates, and potential determinants of specific arthritic disorders (currently osteoarthritis and SLE) or their sequelae; 4) prevention strategies; 5) outcomes research; and 6) education programs for physicians and other health professionals who treat patients with arthritis. Four projects are proposed in the E/E/HSR Component: "Incidence and progression of knee and hip osteoarthritis in Johnston County, NC"; "Emotional contagion between people having arthritis and their spouses"; "Self-
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management, education and outcomes in rheumatoid arthritis"; and "Osteoporosis prevention among women with rheumatoid arthritis receiving oral glucocorticoid therapy". A Numerical Sciences Core provides: methodological consultation and review; development and maintenance of patient databases; data entry and management; biostatistical consultation; education; and computer technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUTATIONS IN PKA GENE TRANSCRIPTS OF LUPUS T CELLS Principal Investigator & Institution: Laxminarayana, Dama; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is an idiopathic autoimmune disorder of indeterminate etiology with multiple Immune effector dysfunctions, which afflicts females in the child bearing years. Protein kinase A (PKA) plays an important role in regulation of immune effector functions of T cells. Previous research has revealed a disorder of type I protein kinase A (PKA-I) enzyme activity in SLE T cells. Recently the applicant has identified mRNA transcript editing of PKA-I RIalpha-subunit and up-regulation of the transcript editing gene, adesosine deaminases that acts on RNA (ADAR) in SLE T lymphocytes. The RNA editing is the co- or posttranscriptional modification of RNA molecules, which results in the insertion, deletion or substitution of nucleotides, mRNA editing plays an important role in the regulation of gene expression and produces phenotypic variability by diversifying the information encoded within the corresponding genomic sequence. The objective of this proposal is to identify the molecular mechanism(s) leading to mRNA transcript editing in RIalphaand RIbeta-subunits of PKA-I and their role in deficient PKA-I isozyme phosphotransferase activity in SLE T lymphocytes. The specific aims of the project are;(1) to quantify mRNA transcript editing in RIa and RIbeta gene transcripts in T cells from patients with SLE and compare this with normal controls as well as patients with rheumatoid arthritis (RA) to characterize its association with SLE pathogenesis;(2) to characterize mutant RIa- and Ribeta-subunit proteins phosphotransferase activity in T cells from SLE patients;(3) to analyze regulation and expression of the ADAR gene in T cells from normal, RA and SLE patients and determine whether there is a selective association with SLE pathogenesis;(4) to quantify ADAR-mediated adenosine to inosine conversion in controls and SLE lymphocyte gene transcripts; and, (5) to quantify ADAR2 transcript editing in T cells of SLE patients and compare this with that in T cells of normals and RA patients to characterize its association with SLE pathogenesis. Therefore, the major goal of this project is to identify RNA editing events in the gene transcripts of SLE T cells and the subsequent dissection of editing mechanisms. The novel data derived from these experiments will prove crucial in addressing questions of functional, biological significance, and regulatory events responsible for deficient PKA-I isozyme phosphotransferase activity in SLE T lymphocytes. Identification of this new mechanism of transcript mutations will provide new insights into the mechanisms of aberrant T cell immune effector functions in SLE and open a new avenue of research to design molecular tools to control aberrant immune functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MYCOPLASMA SUPERANTIGEN & RA MHC SUSCEPTIBILITY ALLELES Principal Investigator & Institution: Cole, Barry C. Professor; Internal Medicine; University of Utah 200 S University St Salt Lake City, UT 84112
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Timing: Fiscal Year 2002; Project Start 01-MAR-1978; Project End 31-MAR-2007 Summary: (provided by applicant): Autoimmune diseases such as rheumatoid arthritis (RA) are currently considered to be due to a complex interplay of host genetics with environmental triggering agents, which include infectious agents bacteria, viruses or mycoplasms. The overall goals of this project are to determine how microbial products such as superantigens (SAgs) might interact with RA MHC-susceptibility alleles to drive a type 1 inflammatory cytokine profile that might trigger active disease in the human host. As a model we will use the newly developed murine class II knockout mice that display various human MHC molecules that predispose to development of collagen arthritis in mice. Mice expressing these molecules will be tested for their cytokine profiles in response to in vivo exposure to the mycoplasma SAg, MAM and other bacterial SAgs using RT PCR and ELISA methodologies. We shall also investigate the mechanisms of any differences seen including the potential role of MHC binding, cell type, role of co-stimulatory molecules, and region of the SAg molecule responsible. Also we will investigate the pathogenetic effects of M. arthritidis in these "humanized" mice and determine strategies to overcome the effect of the superantigen MAM in initiating disease pathogenesis by modification of the cytokine milieu. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NATURAL VITAMIN E IN CONTROLLING SYMPTOMS OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Roubenoff, Ronenn; New England Medical Center Hospitals 750 Washington St Boston, MA 021111533 Timing: Fiscal Year 2001 Summary: We will study the efficacy and safety of supplemental vitamin E therapy in patients with Rheumatoid Arthritis (RA). Since most patients in the United States are treated with at least one and as many as four medications, it is not realistic to study vitamin E therapy in the absence of other medications. Moreover, it is not likely that vitamin E would be used as the sole drug treatment in many Rheumatoid Arthritis patients even with its demonstrated benefit. Thus, the most important clinical trial should be designed to examine the potential use of vitamin E as an alternative/adjunct to NSAID in the typical multi-modality treatment of RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEW RAT MODEL OF AUTOIMMUNE DIABETES AND ARTHRITIS Principal Investigator & Institution: Guberski, Dennis L.; Biomedical Research Models, Inc. 10 New Bond St Worcester, MA 01606 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2003 Summary: (provided by applicant): The objectives of this proposal are to develop and characterize a new congenic rat model with spontaneous autoimmune disease. In Phase 1 we will establish a foundation colony of LEW.1WR1 rats and begin genetic crosses to introgress traits from BBDR/Wor and LEW.1WR strains. This should increase the incidence of spontaneous diabetes and may induce spontaneous arthritis and thyroiditis. The incidence and age of onset of type 1 diabetes, and the occurrence of spontaneous arthritis will be monitored. In Phase 2, select Quantitative Trait Loci (QTL) markers will be used to construct speed a congenic strain with a high incidence of multiple spontaneous autoimmune disorders. Some 5 percent of the U.S. population is affected by one or more autoimmune diseases. Experimental animal models facilitate the study of the pathogenesis of autoimmune diseases and permit the evaluation of
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treatment protocols that are not immediately feasible or ethical in humans. Animal models also provide populations of genetically uniform subjects that can be maintained under environmentally controlled conditions. It is our expectation that this new model of autoimmunity will expedite the development of safe and effective pharmaceutical agents for the treatment of Rheumatoid Arthritis, Type 1 Diabetes, and Hashimoto's Thyroiditis. PROPOSED COMMERCIAL APPLICATION: This research effort will result in a new characterized model of autoimmune diseases. The animal model will generate income by direct sales and contract research within the 15,000 sq. ft. BRM facility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARTHRITIS
NOVEL
IMAGING
TECHNOLOGIES
FOR
RHEUMATOID
Principal Investigator & Institution: Kimpel, Donald L. Medicine; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, LA 71103 Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 31-AUG-2004 Summary: The development of imaging technology for autoimmune diseases is crucial to mechanistically dissect these complex, chronic diseases. Without comprehending the process that leads to disease, it is difficult to develop therapies aimed at ameliorating or preventing autoimmunity. Our proposal is focused on development of imaging model for rheumatoid arthritis (RA), but the models are widely applicable. RA is a debilitating disease that afflicts a large number of people in the U.S. and the world, about 1-2 percent of the world's population. In addition, there are several rodent models that mimic RA. We are particularly interested in developing techniques and reagents to study the process of leukocyte migration from the blood through the synovium and into the joint. We reason that inhibiting leukocyte transmigration will prevent the disease. Indeed, preventing leukocytes from invading tissue will inhibit most autoimmune diseases as well as prevent graft rejection. Intravital microscopy provides a technique to image in vivo the microvasculature at high magnifications. Fluorescence labeled cells can be visualized traveling through the microvasculature and the rate of movement assessed by offline analyses. Various treatments can be administered to modulate in vivo cell movement through the tissues. To develop in vivo intravital microscopy for RA, we will develop a series of transgenic mice with selected cell-types expressing fluorescent proteins. These transgenic mice will allow imaging of selected cell-types in vivo by intravital microscopy. To image changes in cell adhesion molecule expression, which are essential for leukocyte transmigration, we will develop mice expressing fluorescent proteins with similar kinetics as the cell adhesion molecules. To bridge the gap between animal studies and human RA, we will develop a system to image in vivo human leukocyte and human synovium interactions by using the humanized SCID model system. Upon completion of these studies, we will have developed a comprehensive imaging system to study leukocyte migration during autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL IMMUNOTHERAPEUTIC APPROACH TO AUTOIMMUNE ARTHRITIS Principal Investigator & Institution: Geirger, Terrence L.; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006
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Summary: (provided by applicant): Autoreactive T lymphocytes (ATL) are critical regulatory and effector cells for rheumatoid arthritis and other autoimmune diseases. Eradication of these ATL may ameliorate or cure such diseases. Therapies capable of selectively targeting ATL are not available clinically. This proposal describes the develpment of a novel therapy that uses genetically modified T lymphocytes (GM-TL) to selectively eliminate ATL. The GM-TL will be transfected with a chimeric receptor capable of both recognizing ATL and activating the GM-TL. This receptor consists of- a. class II major histocompatability complex (MHC alpha and beta chains, b. covalently linked autoantigenic peptide, and c. activation domain derived from the T cell receptor complex. The ATL T cell receptor will specifically interact with the MHC-peptide complex of the chimeric receptor. This interaction will activate the GM-TL, which in turn will kill or downmodulate the ATL. By using GM-TL to selectively eliminate ATL it should be possible to modulate or abrogate ongoing autoimmune disease. This will be tested using a well characterized murine model for autoimmune arthritis, collagen induced arthritis (CIA). Chimeric construct design will be optimized using in vitro and in-vivo assays of GM-TL activity. These analyses will examine the capacity of GM-TL to kill or modulate the reactivities of type II collagen specific T lymphocytes. GM-TL will then be adoptively transferred into mice prior to, concurrent with, or following the induction of CIA. Pathologic and clinical measures of outcome will be assessed. These experiments will thus provide the initial studies assessing the usefulness of GM-TL in treating autoimmune arthritis. It will establish a precedent for the analagous use of GMTL as a therapy for human autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL OSTEOCLASTOGENIC T CELL FACTOR Principal Investigator & Institution: Rifas, Leonard; Barnes-Jewish Hospital Ms 90-94212 St. Louis, MO 63110 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: Rheumatoid arthritis (RA) is currently considered an autoimmune disease in which a pathologic immune response attacks synovial cells, cartilage and bone resulting in joint destruction and permanent disability. Loss of bone mass in RA is a common clinical problem occurring as both juxta-articular or localized bone loss and generalized osteoporosis leading to the risk of fracture. The juxta-articular bone loss is associated with an increase in blood- derived T cells infiltrating into the synovial cavity. Activated (Act) T cells are believed to mediate most of the tissue destruction, once the inflammation cascade has begun. The Act T cell is a source of cytokines known to regulate bone turnover, such as IL-6 , TNF-alpha and a new member of the TNF receptor family, TRANCE/RANKL/ODF/OPGL, but a causative T cell cytokine is presently unknown. This project is aimed at discovering whether a cytokine produced by activated T cells, that we have recently found regulates the expression of IL-6 in normal human osteoblasts and regulates osteoclast differentiation, is a novel protein. The identification of a novel T cell factor which may be inducing osteopenia in rheumatoid arthritis and perhaps other autoimmune diseases may lead to the development of inhibitory agents which may prove to be of therapeutic efficacy in preventing bone loss in these diseases. Thus our specific Aims are: To purify, characterize and clone the soluble factor(s) produced by activated T-cells that regulates IL-6 production in human osteoblasts and induces osteoclastogenesis; and 2) Prepare recombinant protein and produce antibodies to the T cell factor for future studies of its function. The factor(s) will be isolated using affinity chromatogphy, anion and cation exchange chromatography, gel filtration chromatography and SDS-PAGE. Identification of the proteins as novel will
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be performed by N-terminal or internal sequencing. Internal sequence synthetic peptides will be synthesized and used for the production of polyclonal antibodies. Cloning will be performed using the rapid amplification of cDNA ends (RACE) technique to obtain a partial human cDNA from adaptor-ligated human T cell cDNA. Primers will be designed and the full length cDNA reading frame will be PCR amplified, primers prepared and ultimately a fusion protein cDNA prepared and ligated into a prokaryotic expression vector in order to produce recombinant protein. Antibodies will be prepared against the protein to characterize its function in vitro. We propose to determine whether the T cell factor induces TRANCE in hOB by probing isolated mRNA with labeled cDNA, generated by RT-PCR methods, and Northern blot analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL THERAPEUTIC INTERVENTIONS IN RA Principal Investigator & Institution: Maldonado, Michael A. Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 27-SEP-1999; Project End 30-JUN-2004 Summary: Novel Therapeutic Interventions in Rheumatoid Arthritis: This proposal is organized as a training vehicle that reflects a new direction in my interests to combine mechanistic and translational investigation in rheumatoid arthritis. The core of this proposal is the desire to model the effectiveness and feasibility of two novel therapeutic interventions in RA, autologous bone marrow transplantation and gene therapy. Both of these modalities are already being investigated by other researchers and there is widespread, keen clinical interest. I believe that with this work we can, with a careful and judicious application of available information, obtain both useful insight into etiopathogenesis and practical therapeutic utility. We propose to perform this work as outlined in the following two Specific Aims: Specific Aim 1. The treatment of arthritis by immunoablation followed by stepwise immune reconstitution by drug resistancetransduced stem cells. The existent technologies for bone marrow reconstitution, peripheral blood stem cell harvesting, retroviral transduction, and in vivo drug selection will be combined to allow the gradual development of individual bone marrow chimeras. Several strategies for immunoablative conditioning prior to bone marrow reconstitution will be addressed. This approach will be applied to several mouse arthritis models. We believe that information gained from this work should have an immediate impact on the collaborative efforts that we have already begun with transplantation specialists at The University of Pennsylvania to develop strategies for bone marrow transplantation as a treatment for RA and other Autoimmune Diseases. Specific Aim 2. Gene Therapy in Arthritis as an Investigational Tool. We will expand FasL gene transfer work to other models of spontaneous and induced autoimmune arthritis and perform experiments designed to delineate the cells targeted by this intervention. This will confirm prior observations made in the collagen-induced arthritis model, validate the universality of this therapeutic approach in RA and serve to further understand mechanisms at play. We hypothesize that FasL gene transfer will be effective in preventing and ameliorating arthritis regardless of its etiology so long as the disease is mediated by activated synovial cells expressing Fas molecule. This work will allow me to develop new skills and a wider understanding of the usefulness of gene therapy approaches as both a therapeutic modality and an investigational tool. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OLDER ADULTS & DRUG DECISIONS: COLLABORATION & OUTCOMES Principal Investigator & Institution: Chewning, Betty A. Associate Professor; None; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Midst growing time pressures on physicians, there is a need to maintain and even enhance the quality of physician-patient encounters, particularly for vulnerable, older adults with chronic conditions. Substantial research suggests that older adults are more passive than other age groups during their visits. Hence, physicians may miss key information about patient concerns and regimens that could affect health outcomes. This research addresses gaps identified by literature reviews calling for studies evaluating interventions that efficiently elicit patient pre-visit expectations for physicians and examine the longitudinal effect of expectation fulfillment on patient outcomes. The goal of this research is to study the impact of an intervention that identifies pre-visit concerns of older adult patients and then prompts both patients and physicians to address these concerns in the visit. Older adults' functional status concerns will be identified briefly in the waiting room using a handheld computer. A printout summarizing patient responses will be given both to the physician and patient. We hypothesize that this prompt will affect the nature of the patient-provider encounter in such a way that health outcomes will be improved. To test these hypotheses, a final sample of 580 patients age 60 or older, with a formal diagnosis of rheumatoid arthritis will be enrolled at their clinic visit. A one-year randomized, controlled experiment will be used in which an experimental group patients receive a computerized assessment and prompt about their visit concerns while a control group receives a parallel placebo computerized assessment of their exercise patterns. In both cases, patient assessment summaries are given to the patients and to their physicians in the medical record. Baseline, 6 month and 12 month data will be collected on each patient. We hypothesize improved health status at 12 months for the primary outcomes of pain and physical function. Selected encounter dynamics hypothesized to help explain these outcomes will also be examined. We will audiotape patient-physician encounters to study these interaction dynamics. The primary analyses will examine differences at 12 months between the control and experimental groups using ANCOVA for continuous variables with baseline values of outcomes as a covariate, Dichotomous outcomes will be analyzed primarily by the Mantel Haenszel test and logistic regression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OPTICAL TOMOGRAPHY FOR THE DIAGNOSIS OF JOINT DISEASES Principal Investigator & Institution: Hielscher, Andreas H. Associate Professor; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, NY 10027 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract): The long-term goal of this study is to develop an optical tomographic imaging method to assist in the diagnosis, characterization, and monitoring of joint diseases. In recent years, considerable progress has been made toward these novel imaging methods. The technology for making light transmission measurements on human subjects is now readily available and has been applied in a variety of pilot studies concerned with monitoring of blood oxygenation determination, hemorrhage detection, functional imaging of brain activity, diagnosis of
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Alzheimer disease, and detection of breast cancer. The application of optical tomography (OT) to imaging and diagnosis of arthritis and musculoskeletal disorders has received little attention, even though imaging of joints with OT appears less challenging than breast or brain imaging. One can expect relatively good signal to noise ratios for the transmitted light intensities because of the comparatively small dimensions of, for example, finger joints. Furthermore, changes in the optical properties of various joint components can be expected for most diseases. For example, it is known that with the onset of rheumatoid arthritis, the synovial fluid in the articular cavity becomes increasingly turbid. Therefore, as a specific example, the applicants proposed to initially apply OT to the diagnosis and monitoring of rheumatoid arthritis in the joints of the hand. There remain two key problems to be solved for a successful implementation of an optical tomographic imaging system for joints. 1) Due to the presence of the almost non-scattering synovial fluid in all joints, commonly employed diffusion-theory-based image reconstruction schemes cannot be applied. 2) Due to the strong variation in optical properties within the joints, widely used perturbation-theory approaches to the image reconstruction problem are insufficient. To overcome these deficiencies of currently available reconstruction algorithms, and to develop an optical tomographic system suitable for imaging finger joints, the applicant plans to perform the following studies: (a) Develop non-perturbation 3D-reconstruction algorithm that uses the theory of radiative transfer for the prediction of detector readings. (b) Determine sensitivity of optical tomographic image system to changes in the optical properties of various joint components and evaluate accuracy of image reconstruction. (c) Correlate OT results with clinical findings of rheumatoid arthritis in finger joints. (d) Optimize the performance of the OT imaging system to achieve minimal computation time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL LY333013 AND METHOTREXATE DRUG INTERACTIONS STUDY Principal Investigator & Institution: Branch, Robert A. Professor/Director; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: This is a two-part study (A&B) designed to evaluate the safety and tolerability of commitant LY333013 and methotrexate administration in rheumatoid arthritis patients. Each part of this multicenter study will be conducted independently and will consist of a single blind, placebo controlled, randomized two period crossover. LY333013 is a prodrug of LY315920 which is a potent inhibitor of human non-pancreatic secretory phospholipase A2 (sPLA2). LY333013 is being developed for oral administration in patients with chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, asthma and chronic bronchitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ORAL TYPE II COLLAGEN & MISOPROSTOL TREATMENT OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Postlethwaite, Arnold E.; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001
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Summary: Tis study proposes to test the hypothesis that induction of oral tolerance to type II collagen is effective in rheumatoid arthritis patients when the PGE1 analog, misoprostol, is given to block NSAID effects on oral tolerance." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OSTEOPENIA IN ADULTS WITH HISTORY OF JUVENILE RHEUMATIOID ARTHRITIS Principal Investigator & Institution: French, Anthony R.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001 Summary: Utilizing a previously identified population-based cohort of adults who developed JRA while living in Rochester, Minnesota, between January 1, 1960, and December 31, 1993, we plan to investigate the prevalence and severity of osteopenia in adults with a history of JRA. This will allow testing of the hypothesis that JRAassociated osteopenia persists into adulthood in a significant number of patients placing them at an increased fracture risk. The first specific aim of this study is to utilize dualenergy x-ray absorptiometry (DEXA) scanning to measure bone mineral densities in a cohort of adults with a history of JRA previously identified using the Rochester Epidemiology Project by 1) delineating the prevalence and severity of osteopenia in this population-based cohort of adults with a history of JRA, and 2) comparing bone loss in the appendicular and axial skeleton in this population of patients. The second specific aim is to apply regression analysis techniques in identifying predictors of osteopenia in adults with a history of JRA including age at diagnosis, gender, JRA subtype, Steinbroker functional class, ANA and rheumatoid factor status, steroid use, calcium intake, and exercise level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITIS
PATHOGENESIS
OF
BONE
EROSION
IN
RHEUMATOID
Principal Investigator & Institution: Gravallese, Ellen M.; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a chronic inflammatory disease that often produces severe destruction of articular cartilage and bone. Considerable evidence indicates that bone erosions in RA are produced by osteoclasts (OCs). An essential factor for the differentiation and activation of osteoclasts is receptor-activator of NF-KB ligand (RANKL), which mediates its effects via a specific cell surface receptor, receptor-activator of NF-kB (RANK). Recently, a novel secreted form of RANKL (secRANKL) has been identified which appears to be regulated by a unique promoter. The studies outlined in this proposal are designed to test the hypothesis that that there is enhanced local expression of RANKL at sites of bone erosion in RA and that regulation of RANKL expression in cells at sites of bone erosion is a critical determinant of focal bone loss. Specific Aim 1 will test the hypothesis that RANKL production by cells derived from RA synovium is critical in the pathogenesis of osteoclastic bone erosion. This Aim will address the following questions: What are the exact cellular sources of RANKL at sites of bone erosion in RA? Where is RANKL expressed in relation to OPG expression and to RANK positive OC precursors? Retrieved human tissues will be utilized initially to answer these questions. Cellular expression profiles will be confirmed and the temporal expression of these factors will
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be determined in two murine models of inflammatory arthritis: collagen-induced arthritis (CIA), and the KJBxN model. Dispersed cells from RA synovium will be used to determine the expression of RANKL isoforms in relevant cell types. Finally, the activity of the secRANKL isoform in osteoclastogenesis will be determined in an in vitro coculture model of osteoclastogenesis. Specific Aim 2 will test the hypothesis that T cellderived RANKL is required for bone erosion in RA. Arthritis will be generated in mice in which T cells provide the only source of RANKL, and in genetically engineered mouse strains lacking T cells, in order to definitively determine the role of T cell-derived RANKL in bone erosion. Specific Aim 3 will identify regulatory elements responsible for the constitutive and inducible expression of the membrane-bound RANKL isoform in cell types present in RA, and will test the hypothesis that the NFAT family of transcription factors is critical in the inducible regulation of the memRANKL gene. RTPCR analysis of RANKL expressing cell-types present in focal RA bone erosions demonstrates differential constitutive and inducible expression of the two known RANKL isoforms. Preliminary data also demonstrate a potential role of NFATs in RANKL regulation in T cells. This Aim will provide data on the regulation of RANKL gene expression in cell types present in bone erosion in RA and may lead to new therapeutic strategies for preventing bone destruction in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PAUCI JRA SYNOVIAL CYTOKINES Principal Investigator & Institution: Glass, David N. Professor of Pediatrics and Director; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2001; Project Start 15-JUN-1989; Project End 31-AUG-2003 Summary: This proposal is based on the hypothesis that cytokines have a role in differentiating between the various clinical phenotypes that comprise juvenile rheumatoid arthritis (JRA), the commonest autoimmune rheumatic disease of childhood. Differences in synovial cytokine expression in JRA are likely to complement those already documented with respect to HLA and T cell receptor genes and will also distinguish some types of JRA from rheumatoid arthritis (RA) in adults. It is hypothesized that, based on preliminary data, IL-4 and IL-10 will protect against the more erosive destructive forms of joint disease in JRA and that this effect will be much more clearly demonstrated by the introduction of quantitative methodology. The proposal is based on three specific aims summarized as follows: 1.1 To determine cytokine profiles in joint tissues and fluids of patients with pauci juvenile rheumatoid arthritis and to make comparison with other arthropathies as follows: 1.2. To study the cytokine profile in the clinical evolution of pauci JRA. 1.3. To determine the cellular sources of cytokines which contribute to the pathogenesis of pauci JRA. These aims will be achieved through the use of quantitative methods RNase protection assays, ELISA and, for cellular sources, immunohistochemistry and FACS analysis. Very central to such studies is the availability of a very comprehensive synovial tissue bank now incorporated into the Cincinnati MAMDC. The tissue is added to on an ongoing basis. In the long term, these studies can lead to experimental protocols to explore the cellular mechanisms involved and help in the selection of therapeutic interventions with immune response modifiers in JRA. These interventions are likely to be different, in part, from those used in RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PERIODONTAL DISEASE AND RHEUMATOID ARTHRITIS Principal Investigator & Institution: Mccracken, Michael S. Prosthodontics; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant) Candidate: Michael McCracken, DDS, PhD, is motivated and committed to an academic career involving clinical research. He has demonstrated his ability to complete projects and work independently in the past, and shows the qualtities necessary to become a productive researcher with the education and training provided by this grant. Mentors: Larry Moreland, MD, has as long track record of mentoring clinical researchers. He is the PI of the NIH-funded K30 program at UAB and is the Director of the Pittman General Clinical Research Center. Dr. Marjorie Jeffcoat has also mentored many young investigators, and is Chair of Periodontics at the UAB School of Dentistry and PI on the Oral Health Research Training Grant. Dr. Moreland and Dr. Jeffcoat have collaborated successfully on several previous projects, and are committed to the research outlined in this proposal. Dr. George Howard is the Chair of the Department of Biostatistics in the School of Public Health. He will work with the candidate with the didactic training portion of the training and with statistical support of the research. Dr. Graciela alarcon has a long history in outcomes research in musculoskeletal diseases. Environment: The UAB Medical Center provides depth and diversity of clinical research endeavors as well as the state-of-the-art physical resources that are necessary to support this K23 application. UAB is situated on more than 70 square blocks in the city of Birmingham. With over 16,000 faculty, staff and employees, an annual budget for l999-2000 of over $1.15 billion dollars, and extramural funding exceeding $286 million dollars in 1998-1999, UAB provides a solid environment for this training program. Research: The proposal for this training opportunity is to investigate the severity of periodontal disease in patients with rheumatoid arthritis. The hypothesis is that patients with inflammatory rheumatoid arthritis are more susceptible to inflammation of the periodontal tissues. Furthermore, it is hypothesized that among patients with rheumatoid arthritis, an association exists between the rate of progression of inflammatory arthritis and the progression of periodontal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOGENETICS OF METHOTREXATE IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Bridges, S L.; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-DEC-2006 Summary: Methotrexate (MTX) is one of the most effective drugs for RA, but 20- 30% of patients have suboptimal clinical responses to MTX, and 15-25% have side effects limiting its use. Thus, it is important to elucidate influences on MTX efficacy and toxicity. We will test the hypothesis that single nucleotide polymorphisms (SNPs) in genes encoding key enzymes involved in folate or MTX metabolism or in the mechanism of actions of MTX (e.g. the adenosine pathway) influence clinical responses to MTX. We are uniquely positioned to utilize clinical outcomes (ACR response criteria, radiographic progression and toxicities) and genomic DNA from patients in two completed clinical trials: 153 MTX-treated RA patients from an Immunex trial comparing MTX and etanercept, and 79 MTX-treated RA patients from a UAB trial of folic acid supplementation. HLA DRB1 alleles and a total of 5 known SNPs in the following 4 key genes will be genotyped: 1) 5,10- methylenetetrahydrofolate reductase
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(MTHFR); 2) 5-methyl- tetrahydrofolate-homocysteine methyltransferase (methionine synthase) (MTR); 3) methionine synthase reductase (MTRR); and 4) adenosine receptor A2A [A(2A)R]. These SNPs were chosen on the basis of being common enough in the general population to allow meaningful analyses, their key roles in relevant pathways, and evidence of their biological activity. Through the MCRC Methodology Core, we will look for associations between SNP alleles and MTX efficacy or toxicity. Although these known SNPs are important, SNP haplotypes may be even more informative, aqs they allow characterization of the effect of multiple SNPs working in concert. Therefore, we will use both "in silico" in sequencing approaches to identify novel SNP haplotypes in these 4 and 3 other critical genes: dihydrofolate reductase (DHFR), 5- aminoimidazole-4carboxamide ribonucleotide transformylase (AICAR- T), and aldehyde oxidase (AO). In addition to data mining of public domain and proprietary (i.e. Celera) SNP databases, we will perform SNP discovery on 40 individuals from two racial/ethnic groups [20 African-American (A-A) and 20 Caucasian]. Differences in frequencies of novel haplotype related to disease status or race/ethnicity will be sought by analysis of 108AA Ra patients and 53-AA controls; 336 RA patients (mostly Caucasian); and 800 controls (mostly Caucasian) from established cohorts. Based on results from these studies, the role of selected novel SNP haplotypes on MTX efficacy and toxicity will be tested in patients from the folic acid and Immunex trials. We will compare the predictive power of two approaches to genetic profiling: the single SNP approach and the SNP haplotype approach. These studies may provide clinically useful markers of MTX efficacy or toxicity in RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHYSIOLOGICAL BENEFITS OF MENTAL WELLBEING IN CHRONIC DISEASE Principal Investigator & Institution: Coe, Christopher L. Professor; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2002 Summary: (adapted form the investigator's abstract): This project proposes to evaluate psychological well-being, symptom expression, and endocrine/immune functioning in women with two musculoskeletal conditions, fibromyalgia (FMS), and rheumatoid arthritis (RA). Specifically, the studies will assess whether a capacity to sustain a sense of psychological wellbeing results in severity and self-reported experience of symptoms. The first study will compare women with FMS, RA, and healthy controls across two phases of the menstrual cycle for symptom expression, pain sensitivity, and physiological function. In a second intervention study, an attempt will be made to enhance psychological wellbeing and positive affect with an eight-week training program in women newly diagnosed with RA and FMS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSITIVE AND NEGATIVE REGULATION OF TNF ALPHA SIGNALING Principal Investigator & Institution: Lin, Xin; Microbiology; State University of New York at Buffalo 402 Crofts Hall Buffalo, NY 14260 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by the applicant): Arthritis is a class of disease that affects 43 million Americans. The causes of arthritis are, in general, unknown. However, dysregulated inflammatory and immune responses apparently play very important
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roles in these diseases, since many types of arthritis involve chronic inflammation in different organs. Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine and plays an important role in the inflammatory processes of rheumatoid arthritis. Although TNFalpha is required for regulation of normal inflammatory and immune responses, acute elevated levels of TNFalpha may lead to septic shock during bacterial infection, while chronically elevated levels of TNFalpha are associated with the inflammatory processes of rheumatoid arthritis. Elevated levels of TNFalpha induce expression of many inflammatory genes. Expression of these genes is thought to elicit the swelling, pain and other effects of rheumatoid arthritis. Inhibition of TNFalpha function in vitro and in vivo has been shown to affect several animal models of inflammation. Modulation of TNFalpha levels has also been shown to reduce signs and symptoms of severely active rheumatoid arthritis patients. Thus, understanding the molecular mechanism of TNFalpha function will provide more therapeutic approaches for treatment of arthritic diseases. The present proposal seeks to apply molecular tools to elucidate the precise TNFalpha signaling pathway that leads to activation of NF-kB, a major transcription factor that controls the expression of various inflammatory genes. Specifically, we will investigate how RIP, a key signaling intermediate in the TNFalpha pathway, transmits TNFalpha signals to activate NF-kB. We will also examine how TNFalpha -induced signaling pathway is negatively regulated. Finally, we will use genetic complementation approaches to identify unknown signaling components that are required for TNFalpha -induced NF-kB activation. These studies will provide essential new information about the molecular mechanisms by which TNFalpha signals are transmitted to downstream components that activate the NF-kB family of transcription factors controlling expression of inflammatory genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRESERVING MOBILITY OF JRA CHILDREN USING NOCTURNAL TES Principal Investigator & Institution: Mcguire, John R. Phys Med and Rehabilitation; Medical College of Wisconsin Po Box26509 Milwaukee, WI 532264801 Timing: Fiscal Year 2001; Project Start 20-SEP-1997; Project End 31-AUG-2003 Summary: Therapeutic electrical stimulation (TES) is a modified form of traditional electrical stimulation which involves the use of low-intensity, sub- threshold electrical stimulation applied during sleep. TES is well tolerated and has been used since 1988 in Canada for children with a variety of neuromuscular conditions. The efficacy of TES has not yet been examined in the child with juvenile rheumatoid arthritis (JRA). The purpose of this R29 proposal is to develop and test this innovative use of low-level muscle electrical stimulation as an adjunctive therapy to minimize or prevent movement limitations in the child with juvenile rheumatoid arthritis. Twenty JRA children with bilateral knee joint involvement will be studied during six months while using nocturnal TES as an adjunct to a physical therapy home program. This low-level subthreshold stimulation is done while the child is sleeping six nights a week. This study is very realistic for the child with juvenile rheumatoid arthritis as it done during sleep, the technology is noninvasive, easy to learn and does not add to "the burden of care." The electrical stimulation will be done unilaterally to allow the other leg to serve as a control. The child will be monitored in three major ways: clinical exam, quantitative muscle strength and muscle bulk, and functional assessments. The monthly clinical exam will document bilateral lower extremity A/PROM, MMT of key functional lower extremity muscle groups, leg length, thigh circumference and the Kraus-Weber flexibility test score. The quantitative muscle strength will be assessed by monthly
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isometric knee extensor torque measurements. The functional assessment will include monthly Childhood Health Assessment Questionnaire (CHAQ), and a modified Pediatric Evaluation of Disability Inventory (PEDI). At the beginning and end of the 6 month period, a gait analysis study including physiologic cost index as well as ultrasound measurement of quadriceps muscle thickness will be done. Our hypothesis is that nocturnal therapeutic electrical stimulation will minimize quadriceps weakness and/or atrophy thereby reducing the potential impairments of muscle weakness, knee flexion contracture and gait deviations which may contribute to long-term disability in the JRA population. If the efficacy of this intervention in preserving mobility is demonstrated, future research would explore the underlying neuromuscular and neuroendocrine mechanisms responsible for the clinical effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF TYPE 1 DIABETES WITH MMP INHIBITORS Principal Investigator & Institution: Bleich, David; City of Hope National Medical Center Duarte, CA 91010 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Lymphocyte infiltrates in the islets of Langerhans, "insulitis", is a characteristic hallmark of immune-mediated diabetes in rodent models and human beings. Strategies to prevent invading lymphocytes from reaching the pancreatic beta-cells have been effective in preventing diabetes in non-obese diabetic (NOD) mice. Recently, much attention has been focused on the regulation of matrix metalloproteinases (MMPs) in diseases ranging from metastatic breast cancer to rheumatoid arthritis because these key enzymes regulate tumor cell migration and lymphocyte migration to sites of inflammation. At present, several broad-spectrum MMP inhibitors are being tested in human phase II and Ill trials to determine whether these drugs can prevent tumor metastasis and rheumatoid arthritis. Similarly, we postulated that MMPs play a role in insulitis in NOD mice and possibly human type 1 diabetes. The studies presented here will determine whether a novel broad-spectrum MMP inhibitor can prevent insulitis and diabetes in NOD mice. Six week-old and eighteen week-old NOD mice will be treated with intraperitoneal injections of an MMP inhibitor and followed for development of diabetes. We will evaluate an early treatment protocol (6 weeks of age) to see if MMP inhibition can prevent insulitis and a late treatment protocol (18 weeks of age) to see if MMP inhibition can prevent diabetes once insulitis has progressed. Furthermore, splenic and pancreatic lymph node T cells will be obtained from NOD mice and challenged in vitro with glutamic acid decarboxylase 65. We will assess the Thl/Th2 profile of lymphocytes isolated from these two anatomic sites and whether MMP inhibition can alter the cytokine profile. In collaboration with the University of Arizona, we will evaluate the role of MMPs and their inhibitors in Tlymphocyte development and migration using an in vitro fetal thymic organ culture (FTOC) model. This system has been called "in vitro IDDM" because NOD thymic T lymphocytes can target and infiltrate NOD pancreatic islets when the two organs are cocultured. Since MMP inhibition not only regulates cell migration, but apoptosis, we will perform dose and time courses with MMP inhibitors to determine whether this strategy can alter thymic T-lymphocyte selection and maturation. Finally, TNF-alpha can regulate the production of diabetogenic T-cells and regulatory NKT cells bearing both natural killer and T-cell phenotypes (DX5+ cells) in the FTOC model. Cell membrane bound metalloproteinases called ADAMs (A Disintegrin And Metalloproteinase) process membrane-bound pro-TNF-a to the biologically active cytokine. Thus, we will determine whether MMP inhibition can downregulate intrathymic TNF-a production
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and increase the levels of NKT cells. We will determine levels of CD4+,CD8+, and NKT cells using flow cytometry. We anticipate that these studies will give us supporting data to initiate a human trial to treat pre-type 1 diabetic patients with a broad-spectrum MMP inhibitor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROPERTIES OF SHARED EPITOPE SPECIFIC T CELLS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Albani, Salvatore; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: It is the hypothesis of this grant application that the pathogenesis of rheumatoid arthritis (RA) depends not upon the absolute numbers of T cells in the blood or the joints, but rather upon the relative percentages of auto-antigen specific T cells that produce and respond to pro-inflammatory and anti-inflammatory signals, including cytokines and chemokines. These T cell populations may be the target for therapeutic intervention. In preliminary experiments that prompted this grant application, we have shown that: i) peptides of bacterial origin (E. coli dnaJ heat shock protein) are strong immunogens in RA patients. dnaJ shares with HLA DRB1*0401 the susceptibility sequence to RA (shared epitope); ii) T cells in the blood RA patients that react with the shared epitope can be identified and isolated, using a novel technical approach; iii) T cell receptors usage and patterns of cytokine production by these shared epitope specific T cells can be analyzed. Based upon these initial results, we now need to test our hypothesis in a larger cohort of RA patients with different disease courses, and responses to treatment. Thus, the aims of this project are: 1. To characterize frequencies, function and phenotypes of T cells in RA patients reactive with the shared epitope. Parameters to be studied will include cytokine production, T cell receptor usage and membrane markers of activation and memory. Chemokine receptors will also be studied. 2. To determine the effects of disease activity and severity, and of slow acting anti rheumatic drugs, on function and phenotype of the shared epitope specific and bystander T cells. 3. To develop methods to modulate the Th1-type phenotype of shared epitope specific T cells, using in vitro immune manipulation with altered peptides. The long term objectives of this project are: i) to contribute to a better understanding of T cell-mediated events in the pathogenesis of rheumatoid arthritis; (ii) to develop paradigms for the prediction of disease outcome, and for evaluation rapidly new models of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTECTIVE ROLE OF INNATE IMMUNITY IN AUTOIMMUNE DISEASE Principal Investigator & Institution: Carroll, Michael C. Professor; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-MAY-2007 Summary: The overall goal of this Program is to examine a protective role for innate immunity in autoimmune disease. Two murine models of autoimmunity will be characterized, i.e. systemic lupus erythematosus and rheumatoid arthritis. Four highly interrelated projects are proposed involving five senior investigators. The underlying theme connecting the four projects is the intimate role innate immunity plays in antigen clearance. Three of the projects will examine how self-reactive B- lymphocytes are
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negatively regulated by antigen in two well- characterized immunoglobulin transgenic models, i.e. hen lysozyme and dsDNA. Clonal deletion and receptor editing of selfreactive B- lymphocytes will be examined in mice deficient in innate proteins DNAse I, IgM, MBL, C1q, C4 and receptors CD21/CD35. Moreover, novel transgenic mice bearing an auto-reactive transgenic receptor or deficiency in Fas will be constructed using a conditional knock-in approach. The fourth project will examine if innate immunity is involved in T cell tolerance and/or elimination of self-antigen in the rheumatoid arthritis T-cell transgenic model. The significance of the program is that it not only addresses fundamental questions on regulation of adaptive immunity but could lead to novel therapies. Dissection of common pathways of innate immunity that protect against autoimmune disease could lead to therapeutic approaches with broad applications. A major strength of the Program is that it brings together senior investigators, each with specialized expertise, to interact in a synergistic manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PULSE THERAPY IN SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS Principal Investigator & Institution: Lovell, Daniel J. Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2000; Project Start 30-SEP-1998; Project End 31-OCT-2003 Summary: (adapted from applicant's abstract): Systemic juvenile rheumatoid arthritis (sJRA) is associated with significant long term morbidity and mortality. Current therapies including methotrexate are considered ameliorative rather than remission inducing or curative. There have been anecdotal reports suggesting that pulse therapy with intravenous corticosteroids, cyclophosphamide, and methotrexate may induce prolonged remissions in sJRA. Therefore, the objectives of this study are to determine and compare the ability of two pulse therapy regimens to induce remission in sJRA of less than 12 months duration during a 9-month, open-label, randomized, actively controlled clinical trial. The first pulse therapy regimen is composed of intravenous methylprednisalone 30 mg per kg per day (1 gram max) for three consecutive days, intravenous cyclophosphamide 0.4 grams per meter2 BSA on the third day, and up to 20 mg per meter2 per week of methotrexate. The second pulse therapy regimen is identical to the first, except no cyclophosphamide is given. Up to five cycles of these regimens may be given over a 9-month period. Patients in both groups may also receive background medications including a non-steroidal, anti-inflammatory drug and up to 0.5 mg/kg/d of oral prednizone. The primary outcome to measure the effect of this therapy will be the proportion of patients who achieve clinical remission according to the ACR criteria for remission in rheumatoid arthritis. Secondary outcome measures of effectiveness include proportion of patients who demonstrate clinical response according to the preliminary definition of improvement for JRA. In addition, time per remission and the duration of remission will be compared between the two groups among patients who do remit. Specific Aim 2 is to determine and compare the short and intermediate term (18 months) safety profiles of the pulse therapy regimens as defined in Specific Aim 1. Long term goals of the project are to determine and compare the longer-term safety profiles of this treatment regimen. This will involve analysis of patient/parent-derived data obtained by mail or phone follow-up to detect significant medical problems and reproductive or neoplastic complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: QUINAPRIL AND LOSARTAN IN FIBRIOLYTIC BALANCE Principal Investigator & Institution: Vaughan, Douglas E. Chief, Division of Cardiovascular Medici; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001 Summary: Test the effectiveness of a new treatment for patients with rheumatoid arthritis. Anti-TNF Chimeric Monoclonal Antibody is a biological product which acts to inhibit the action of tumor necrosis factor alpha, a major mediator of inflammation in rheumatoid arthritis. We are in the recruitment and enrollment phase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RA ASSOCIATED AUTOIMMUNITY IN HIGH RISK POPULATIONS Principal Investigator & Institution: Holers, Michael; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 14-AUG-2006 Summary: The long-term goal of these studies is to identify during the pre-clinical phase of disease those healthy individuals who are at sufficiently high risk for developing Rheumatoid Arthritis (RA) so that a rational primary prevention strategy can be employed. Such a strategy in RA or other autoimmune diseases has been previously thought to be unfeasible. However, extensive experience gained at the University of Colorado Health Sciences Center (UCHSC) in Type 1 or Insulin-Dependent Diabetes Mellitus (IDDM), an autoimmune disease in which disease- related autoimmunity can be detected in the pre-clinical state, has demonstrated that by using several informative strategies one can identify individuals at risk for the development of clinical disease in both the general population and within families. These studies are part of the Diabetes and Autoimmunity Study in the Young (DAISY). With this information, investigators in DAISY are currently employing prevention strategies designed to block the development of clinical signs and symptoms of disease in children with autoimmunity but no significant islet cell dysfunction yet detectable. Using collaborative investigators from the DAISY project, we propose in this funding period to use a very unique population resource of >21,000 HLA typed children and their parents identified during a general population screen in DAISY, as well as adult patients with RA identify by outreach efforts, in order to develop three unique cohorts of individuals at risk for RA. Using these cohorts, we will test the primary hypothesis that pre-clinical evidence of RA- related autoimmunity can be detected in a substantially increased percentage of healthy children and adults who are at increased risk for the development of RA as compared to controls. If this hypothesis is true, our secondary hypothesis will then be that genetic and environmental factors can be identified in these individuals that strongly correlate with pre- clinical RA-related autoimmunity. To test these hypotheses, we propose the following three Specific Aims. Specific Aim #1: Utilize DR4 HLA typing information in the DAISY newborn cohort to identify and characterize DR4-positive parents who are at increased risk for RA in order to determine the age-specific prevalence and incidence of RA- related autoimmunity. Specific Aim #2: Utilize HLA typing information in the DAISY newborn cohort to identify and characterize children for whom the presence of single of compound heterozygote DR0404/0401 alleles substantially increases the risk for RA in order to determine the age-specific prevalence and incidence of RA-related autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RECEPTOR DIVERSITY IN RECOGNITION OF INFLUENZA HA Principal Investigator & Institution: Caton, Andrew J. Associate Professor; Wistar Institute Philadelphia, PA 191044268 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 28-FEB-2007 Summary: (provided by applicant): The objective is to analyze factors governing tolerance and autoreactivity among murine CD4+ T and B cells in transgenic mice that express the influenza virus PR8 hemagglutinin (HA) as a well-characterized neo-self antigen (HA Tg mice). In particular, how the distinct specificities of separate populations of CD4+ T and B cells affect their negative selection by the neo-self HA, and processes that can lead to the activation of autoreactive lymphocytes in HA Tg mice will be examined. Aim 1 will examine the selection and functional potential of autoreactive CD4+ T cells that have low avidities for a self-peptide in TCRxHA Tg mice. Whether activation increases the sensitivity of low avidity T cells to the extent that they become responsive to a self-peptide will be determined. In addition, how TCR specificity and/or virus infection contributes to the ability of CD4+ T cells to mediate autoimmune myocarditis in HA Tg mice expressing the HA in cardiac tissue will be assessed. Aim 2 will examine factors governing the phenotypic potentials of B cells that express characteristic variable region clonotypes, that are representative of primary versus memory responses to the HA in virus-immunized BALB/c mice, and that differ in their sensitivity to negative selection in HA Tg mice. Whether selection into different B cell subsets and/or affinity for the HA determines the distinct phenotypic potentials of B cells expressing these clonotypes will be evaluated. In addition, whether autoreactive CD4+ T cells rescue primary response B cells from deletion and/or promote memory B cell formation in response to the neo-self HA will be assessed. Aim 3 will examine the processes that lead to the development of organ-specific autoimmunity. An autoimmune syndrome resembling rheumatoid arthritis develops in TCRxHACII mice in which the HA is expressed on antigen presenting cells, and the cellular interactions that lead to its development will be assessed. Whether virus infection provokes autoimmunity in TCRxHACII mice expressing low affinity CD4+ T cells and/or CD4+ T cells directed to a cryptic self-peptide will also be examined. These studies will provide fundamental insights into the mechanisms of immune tolerance, and will have direct relevance to understanding the processes that lead to the development of autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF COLLAGENASE 3 GENE EXPRESSION BY CYTOKINES Principal Investigator & Institution: Rahman, Mahboob U. Instructor of Medinice; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 14-APR-1998; Project End 31-DEC-2002 Summary: The overall goal of this proposal is to study the cytokine-mediated regulation of collagenase-3 gene expression in order to better understand the mechanisms involved in the degradation of articular cartilage in rheumatic diseases such as rheumatoid arthritis (RA) and osteoarthritis ( OA). OA is the most common form of joint disease and is second only to cardiovascular disease as a cause of early retirement and disability. The destruction of hyaline articular cartilage is the hallmark of OA and disabling RA. Although various therapeutic regiment can cause symptom relief, no regiment has been proven to retard progression of articular cartilage degradation. In disease there is either a suppression of normal chondrocyte functions or in the constitutive inability of these
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cells to match the rate of repair with the increased rate of degradation of the matrix. Various cytokines and inflammatory mediators have been shown to either derange the synthetic functions of the chondrocytes of increase cartilage matrix catabolism by regulating various matrix-degrading enzymes, including the collagenases. Collagenase3 is specifically expressed in skeletal cells including chondrocytes and has been shown to have an additional cleavage site when compared to other collagenases. It has aggrecanase and gelatinase activity as well. It's expression is response to IL-1 and other inflammatory cytokines. Thus it may play a significant role in physiological skeletal remodeling and destruction of cartilage in disease. The collagenase-3 gene has been recently cloned, but the role of various cytokines in the transcriptional regulation of this gene is yet to be elucidated. We have cloned the collagenase-3 promoter from a human genomic DNA library. We will prepare reporter gene constructs (CAT) containing collagenase-3 promoter and transfect immortalized human cell lines and analyze the effects of selected cytokines/ligands e.g. IL- 1beta, TNF-alpha and TGF1-beta. The ciselements and trans-acting factors will also be characterized employing transfection and DNA-binding assays. We will also develop transgenic mice containing the collagenase promoter- beta-galactosidase fusion gene to analyze the expression and role of collagenase in development of arthritis in vivo. Transgenic mice will be treated with IL1ra, TNFR1-IgG1 fusion protein, and dexamethasone after induction of arthritis and the role of cytokines/ligands in the control of expression of collagenase and its role in development of arthritis will be elucidated. This proposal will provide insight into the mechanisms involved in the expression of collagenase-3 by cytokines and thereby may provide targets for developing novel therapeutic measures to inhibit cartilage destruction in joint disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF COLLAGENASE GENE EXPRESSION Principal Investigator & Institution: Brinckerhoff, Constance E. Professor; Medicine; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2001; Project Start 01-MAR-1980; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract) The overall goal of these studies is to understand the role of matrix metalloproteinases (MMPs) in the severe and irreversible degradation of cartilage, bone and tendon that accompanies rheumatoid arthritis. The application proposes to continue examining molecular mechanisms controlling expression of the MMP-1 (collagenase-1) as well as MMP-13 (collagenase-3). Previous and preliminary studies have characterized the regulation of MMP-1 and MMP-13 by IL-1 and TNF-alpha in rabbit synovial fibroblasts and human chondrosarcoma cells. These studies and recent cloning of the rabbit MMP-13 gene in the applicant's laboratory indicate that the rabbit is an appropriate model for assessing the relative contributions of MMP-1 and MMP-13 in the invasion/degradation of collagen in RA. Preliminary studies also identified a single nucleotide polymorphism (SNP) within the human MMP-1 promoter, which creates a new PEA3 site that binds Ets transcription factors and enhances transcription of MMP-1 in human fibroblasts. These results suggest that RA patients with this allele may display heightened MMP-1 expression and particularly erosive synovitis. Thus, the specific aims are to (1) recapitulate the pathogenesis of RA in a rabbit model of polycation-induced arthritis and correlate the temporal expression of MMP-1 and MMP-13 gene with the erosive/invasive ability of synovial tissue through a matrix of type II collagen; (2) examine the mechanisms regulating expression of the endogenous MMP-13 gene in chondrocytes and fibroblasts treated with TNF and IL-1 and understand its regulation at the molecular level; and (3) determine the
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frequency and functional significance in patients with RA of a SNP in the human MMP1 promoter that augments transcription. These studies are expected to increase our molecular understanding of the relative roles of the two interstitial collagenases that are central mediators of the connective tissue destruction accompanying RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF INFLAMMATORY GENES IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Dong, Chen; Immunology; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that affects a large human population. CD4+ helper T (Th) cells play a major role in RA, by mediating autoantibody production and inflammatory reactions in the joint tissue. In the autoimmune reaction, auto-reactive Th cells differentiate into Thl cells that make IFNgamma and TNFalpha and regulate cellular immunity. However, animals deficient in IFNgamma or its receptors exhibited greater susceptibility to CIA, suggesting that other Thl cytokine may be more important in autoimmune function. Th activation and function are regulated by co-stimulatory molecules. ICOS is a novel co-stimulatory receptor expressed by activated T cells. ICOS ligand, B7H is constitutively expressed on B-cells and induced in non-lymphoid tissues and cells as a result of inflammatory reactions. Although ICOS has been shown by us and others to be important for Th2 differentiation, we recently found ICOS-/- mice onDBA/1 background to be completely resistant to CIA. This resistance is associated with a selective deficiency of IL-17, a cytokine widely implicated in RA. We further found IL-17 is selectively expressed by Thl cells differentiated in vitro in an ICOSdependent manner. However, the molecular mechanisms by which IL-17 is regulated in Th differentiation and how it exerts its function in RA have been poorly defined. Therefore, we propose to utilize the gene-expression profiling tools to study these mechanisms. First, we will characterize the gene expression in IL-17+ mouse Thl cells. We will assess if IL-17 is expressed by a distinct subset of Thl cells that initiate the arthritis. Secondly, we will compare gene expression profiles of ICOS+/+ and ICOS-/Thl cells to identify factors regulating IL-17 expression. Thirdly, we will examine the role of IL-17 on inflammatory responses of the joint tissue. We will examine gene expression changes in the synovial fibroblasts and macrophages after exposure to IL-17 in vitro and in vivo. Furthermore, we will extend the results we yield in our animal studies to the human patient samples. This study will greatly advance our knowledge on the specific regulation and function of IL-17 in RA, and will likely generate novel diagnostic markers and therapeutic targets for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF INFLAMMATORY RESPONSES Principal Investigator & Institution: Reimold, Andreas M. Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 20-JUL-1998; Project End 30-JUN-2003 Summary: (Adapted from Investigator's abstract): Autoimmune and inflammatory conditions such as rheumatoid arthritis are characterized by cellular infiltrates and the cytokines they secrete. The stimuli controlling cellular activation are received at the surface of inflammatory cells by receptors, transmitted by a signal transduction cascade
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to selected transcription factors, and result in modulation of gene transcription. The transcription factors that control the inflammatory response are therefore attractive candidates for therapeutic intervention in rheumatic diseases. The role of the transcription factor hXBP-1 (human X-box binding protein- 1) in inflammation has recently begun to emerge. hXBP-1 is strongly expressed in rheumatoid synovium, and in vitro studies suggest that hXBP-1 is involved in the control of MHC class II expression and in the B-lymphocyte differentiation pathway. However, the mechanism of action for hXBP-1 in these processes remains unknown. In order to gain a better understanding of the functions of hXBP-1, they have used gene targeting to generate mice deficient in hXBP-1 and have found an embryonic lethal phenotype. Therefore, they have additionally produced hXBP-1-deficient embryonic stem cells in order to generate hXBP1-deficient/RAG-2-deficient chimeric mice for study of B- and T-lymphocytes lacking hXBP-1. They will use hXBP-1-deficient cells and cell lines to establish if hXBP-1 is phosphorylated upon activation, and to define the proinflammatory stimuli and cellular stressors that act on hXBP-1. The preferred target genes for hXBP-1 will be identified by using a modified subtractive hybridization strategy. This knowledge will be applied to the HTLV-1-transgenic mouse model of rheumatoid arthritis to assess if a dominantnegative mutant of hXBP-1 reduces joint inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF INTEGRIN ALPHA 4 BETA 1 Principal Investigator & Institution: Ginsberg, Mark H. Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2001; Project Start 01-AUG-1980; Project End 31-JAN-2006 Summary: (Applicant's Description Verbatim): lntegrin alpha4beta1 plays a central role in the trafficking of mononuclear leukocytes and is a potential therapeutic target in chronic inflammatory diseases such as rheumatoid arthritis. Continued support is requested for an analysis of the signaling properties of this integrin. Alpha4beta1 promotes increased cell migration and less cell spreading, stress fiber, and focal adhesion formation than other beta1 integrins. The applicant discovered that the alpha4 cytoplasmic domain binds tightly to the signaling adapter, paxillin. Furthermore, absence of paxillin or a mutation in the a4 tail that disrupts its binding reverses these biological effects. Consequently, the applicant proposes the hypothesis that the paxillinalpha4 interaction is responsible for the unusual biological responses to alpha4 integrins. To test this, he will map the paxillin-binding site in the alpha4 tail and define mutations that disrupt the interaction. He will introduce these mutations into intact integrins, and examine their effects on cell migration, cell shape, and organization of the cytoskeleton. Conversely, he will use the mapping information to engineer the paxillin binding sites in other integrin a cytoplasmic domains. He will determine whether gain of paxillin binding causes changes in cell shape and cell migration. Furthermore, he aims to assess the consequences of the alpha4-paxillin interaction for downstream signaling events such as activation of Jun Kinase and Focal Adhesion Kinase. To further assess the biologic significance of the alpha4-paxillin interaction, the applicant proposes to generate and characterize mice bearing mutations in the a4 tail that disrupts paxillin binding. He aims to analyze alpha4 integrin-dependent functions in mononuclear cells derived from such mice. As another test of the hypothesis, the applicant proposes to identify alpha4 cytoplasmic domain-binding sites in paxillin and assesses the effects of mutation of these sites on alpha4 specific responses. He proposes to analyze potential downstream "effectors" of paxillin by mutating their binding sites in paxillin and assessing the effects of the mutations on alpha4-specific signaling. Finally, the applicant
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has discovered that alpha4beta1 like other integrins, undergoes active affinity modulation. He hypothesizes that the affinity changes in alpha4beta2 are important in its biological functions. To test this hypothesis he will derive cell lines that manifest defective alpha4 integrin activation or discover subtle mutations in alpha4 that disrupt the activation process. The effect of these mutations on alpha4-dependent adhesive and migratory functions will be assessed. These studies will provide important fundamental insights into the functioning of integrin alpha4beta1 and may identify novel therapeutic targets for chronic inflammatory diseases such as rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF THE MAP KINASE PATHWAY IN THE CD4+ T CELLS Principal Investigator & Institution: Lu, Binfeng; Immunology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Previous studies have demonstrated that the p38 and JNK MAP kinase pathways are prominently activated by TCR stimulation in Th1 cells but not in Th2 cells. These data suggest that the p38/JNK MAP kinase pathways are regulated in helper T cells depending on the cell context. Preliminary data show that GADD45gamma and GADD45beta are highly expressed in Thl cells versus Th2 cells. Since GADD45 family proteins were shown to activate both JNK and p38 when overexpressed in COS-7 cells, they hypothesize that these molecules are responsible for the elevated p38 and JNK activities in Th1 cells and likely critical for the function of Th1 cells. Consistent with the hypothesis, in Th1 cells, deletion of GADD45gamma significantly elevated the threshold of TCR stimulated activation of p38 and JNKs. In addition, GADD45gamma also mediates Th1 functions such as IFN-gamma production and delayed type hypersensitivity. In addition to their roles in the function of Th1 cells, they discovered that GADD45beta is induced by TNF-alpha in synoviocytes. Therefore, they hypothesize that GADD45 family molecules may regulate the activation of the p38/JNK MAP kinase pathways in synoviocytes by inflammatory cytokines. Since the p38/JNK MAP kinase pathways are involved in the pathogenesis of rheumatoid arthritis, they hypothesize that GADD45 family proteins are involved in the development of such disease. To further study the role of GADD45 pathway in mediating the activation of p38/JNK MAP kinases and its relevance to rheumatoid arthritis, they propose to: Aim 1. Study the role of GADD45 pathway in mediating TCR stimulation using genetic and bioinformatic approaches. Aim 2. Study the role of GADD45 protein in mediating the activation of the p38/JNK MAP kinase pathway by cytokines. Aim 3. Study the effect of mutation of GADD45gamma, GADD45beta, or MEKK4 in murine collagen induced arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATORY MECHANISMS OF INFLAMMATORY OSTEOLYSIS Principal Investigator & Institution: Abu-Amer, Yousef; Associate Professor; Orthopaedic Surgery; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Inflammatory osteolysis, as in rheumatoid arthritis (RA), reflects increased osteoclast (OC) activity. OC recruitment is mediated via RANKL interaction with its receptor, RANK. We and others have established that TNF plays a
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key role in the pathogenesis of inflammatory osteolysis and other forms of inflammation-induced bone loss Central to this proposal are our observations that RANKL and TNF both activate NF-kB and AP-1/cJun signaling pathways, and TNF dramatically stimulates RANKL-induced osteoclastogenesis via. TNFr1. Reduced osteoclastogenesis correlates with diminished NF-kB and c-Jun activation by TNF and RANKL in TNFr1-/- cells. These facts, together with our findings that RANKL and TNF stimulate recruitment of TRAF2 and TRAF6 to their receptors, points to a possible intracellular coupling between these two receptors which, in turn, leads to a super osteoclastic response. Supporting this hypothesis is the fact that RANK utilizes the traditional TNFr-recruiting machinery to activate NF-kB and c-Jun signaling pathways. Taken together, our data point that enhanced osteoclastogenesis (as in inflammatory osteolysis) requires the presence of TNFR1. Therefore, understanding the exact mechanisms by which TNF promotes RANKL-dependent osteoclastogenesis and thus, inflammatory osteopenia, may provide a foundation for developing osteoclast inhibitory strategies. Molecular inhibition of osteoclastogenesis by anti-inflammatory cytokines is under-investigated. IL-4, the major soluble factor secreted by T helper-2 (TH2) lymphocytes, is an anti-inflammatory cytokine and a potent inhibitor of osteoclast differentiation. However, its anti-osteoclastic mechanism is unknown. We provide evidence that IL-4 blocks RANKL-induced NF-kB activation in osteoclast precursors. More importantly, using STAT6-/- cells we find that inhibition of NF-kB activation and osteoclastogenesis by IL-4 is a STAT6-dependent event. Given the inflammatory and osteoclastogenic role of NF-kB and that STAT proteins can act as transcriptional inhibitors, our observations raise the possibility that IL-4 exerts its anti-osteoclastogenic effects via inhibition of RANKL activation of NF-kB and perhaps AP-1 signaling pathways. Understanding the molecular steps of IL-4/STAT6-inhibition of osteoclastogenesis may provide the foundation for controlling inflammatory osteolysis. Our Specific Aims are to determine: 1) the mechanism(s) by which the TNFr1 signaling pathway stimulates RANKL-mediated osteoclastogenesis, 2) the mechanism(s) by which IL-4 inhibits RANKL-mediated osteoclastogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RELAXATION RESPONSE,SOMATIC STYLE & RHEUMATOID ARTHRITIS Principal Investigator & Institution: Barsky, Arthur J. Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 15-JUL-2001; Project End 30-JUN-2006 Summary: This is a three-armed randomized, controlled intervention trial to determine the effect of relaxation response training (RR) and of relaxation training combined with cognitive/behavioral therapy (RRCBT) on the symptoms, functional ability, role impairment, and medical care utilization of patients with rheumatoid arthritis (RA). We will also examine the role of selected attitudes and beliefs expected to moderate the treatment response and predict outcome. These same attitudes and beliefs are also hypothesized to predict the incidence of medication side-effects and to be associated with the inter- individual variability in RA symptoms seen among patients with RA of comparable severity and extent. Three-hundred and seventy- five RA patients will undergo a baseline assessment of the independent variables (including hypochondriacal health anxiety, bodily amplification, normative beliefs about health, and alexithymia) and covariates (including RA severity, life stress, social support, and psychological distress). They will then be randomly assigned to RR, RRCBT, or an attention control group. The outcome variables (RA symptoms, functional ability, role impairment, and
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medical care utilization) will be measured immediately after treatment, and 6 and 12 (the primary outcome) months later. The effect of treatment will be determined by comparing each intervention group to the control group, and by within-subject comparisons before and after treatment. Additional group analyses will be conducted to determine the influence of cognitive and attitudinal variables on outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RHEUMATOID ARTHRITIS: PREDICTORS OF THERAPEUTIC RESPONSE Principal Investigator & Institution: O'dell, James R. Professor and Chief of Rheumatology; Internal Medicine; University of Nebraska Medical Center Omaha, NE 681987835 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (investigator's abstract): Rheumatoid arthritis (RA) is a common, chronic disease that causes substantial morbidity and mortality while utilizing a large portion of health care resources. While recent therapeutic approaches have provided significant improvement in patients' functional status and well being, the selection of specific therapy remains empiric and highly variable. The ability to use surrogate markers to predict which patient is likely to respond to certain anti-rheumatic therapy would offer major advantages in the management of this chronic and progressive disease. Recent evidence has suggested a clear role for proinflammatory cytokines, membrane metalloproteinases, and genetic factors in influencing the severity and progressive nature of the disease. Thus, it is reasonable to suggest that the status of these factors may allow the characterization of patients into 'responder' versus 'non-responder' groups. The intent of this proposal is to utilize material from carefully controlled clinical trials where patient groups have been identified as either responding or not responding to specific therapies. This material will be evaluated for various cytokine, MMP, and genetic factors that may predict response to therapy. The hypothesis is that determining specific patient cytokine profiles, membrane metalloproteinase levels, and/or genetic phenotypes may predict the 'responder/non-responder' status of patients with specific therapy intervention. This hypothesis will be tested by three specific aims which are: Specific Aim #1 - correlate the response of patients with RA to specific therapies with changes in cytokine, matrix metalloproteinases and/or acute phase protein levels. Specific Aim #2 - correlate the response of patients with RA to specific therapies with HLA-DRB1 subtyping and non-MHC gene polymorphism. Specific Aim #3 - develop strategies for initiating prospective clinical trails using predictive cytokine, matrix metalloproteinase, and genetic factors. The unique strength of this proposal is the patient serum and DNA sample bank that is available from several controlled, randomized, blinded, clinical protocols that clearly define patients as responder or nonresponder. Retrospective analysis of this information can be utilized to plan prospective clinical trials using potentially predictive patterns of cytokine, matrix metalloproteinases, and genetic factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRATEGIES
RHEUMATOID
ARTHRITIS--ADHERENCE
INTERVENTION
Principal Investigator & Institution: Dunbar-Jacob, Jacqueline M. Professor; Health and Community Systems; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260
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Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 28-FEB-2003 Summary: Nonadherence to prescribed medication is a major problem in the management of chronic disease. Estimates are that about 40 percent to 60 percent of patients adhere with the costs of nonadherence approaching 10 billion dollars per year. Yet very few randomized, controlled intervention trials have been conducted to guide efforts to improve adherence. The disease represented in the limited number of intervention studies include asthma, hypertension, epilepsy, schizophrenia and acute infection. No studies, other than our own, have been done with patients with rheumatoid arthritis (RA). The adherence rates for persons with RA are equivalent to those found for other chronic disorders. Adherence is particularly important for this population, as pharmacological treatment is directed toward the suppression of inflammation and resulting synovitis and the prevention of disability. In a recently completed study, we conducted a randomized, controlled intervention study of a behaviorally based, 12- session, telephone counseling intervention on adherence. We found differences in adherence between an intervention and usual care group of 12.3 percentage points (z=minus 1.91, p is less than or equal to.03) with changes in adherence associated with changes in pain (rs=minus.29, p is less than or equal to.01). Although promising, differences in adherence at six month follow-up were not statistically significant (p is less than or equal to.07). In this project we propose to replicate our intervention study using telephone counseling as well as to examine a less costly method of intervention delivery, mailed self-instruction, and further to examine the efficacy of an ongoing maintenance strategy on adherence, clinical outcomes, and costeffectiveness. Specifically our aims are to (1) compare the effect of telephone delivered intervention, mailed self-instruction, and usual care on adherence to pharmacological therapy, clinical outcomes, and cost-effectiveness as well as to (2) compare the effect of an adherence intervention plus maintenance intervention with adherence followed by observation only and usual care on adherence to pharmacological therapy, clinical outcome, and cost-effectiveness. We propose to recruit from two practice sites and randomize 198 persons with rheumatoid arthritis who report some difficultly with the medication regimen. Using a randomized, controlled design, patients would be randomized into telephone intervention, mailed self-instructional intervention, or usual care for a six month intervention period. Following the intervention phase, the two intervention groups would be randomized within groups to maintenance intervention or observation only for an additional six months. The usual care group would continue to be followed to generate natural history data for comparison purposes. Should one or more of the strategies prove successful, intervention manuals would be disseminated for use by nurses working in clinical settings with this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RO45-2081 FOR PATIENTS WITH RHEUMATOID ARTHRITIS Principal Investigator & Institution: Polisson, Richard P.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF CD30: CD153-PATHOGENESIS OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Cerutti, Andrea; Pathology and Laboratory Medicine; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2004 Summary: (provided by investigator): Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of synovial membranes and progressive joint destruction. In RA, B cells produce large amounts of IgM as well as class switched IgG and IgA that, by accumulating in the joints as highly reactive immunocomplexes, play a central role in the pathogenesis of synovitis. The mechanisms underlying the dysregulation of Ig class switching and antibody production in RA patients remain elusive. Human B cells initiate class switch DNA recombination (CSR) and antibody production upon engagement of CD4O by CD154 (CD4O ligand), a molecule expressed by T cells a few hours after activation by antigen. Later on, T cells express CD3O, a TNF receptor family member that negatively modulates both T and B cell immune responses. Engagement of T cell CD30 by B cell CD153 (CD30 ligand) inhibits CD40-mediated CSR and antibody production in two ways: by interfering with the CD40 signaling pathway and by hampering the CD3-mediated up-regulation of CD154. Dendritic cells reverse the CSR-inhibitory activity of CD3O+ suppressor T cells by inducing metalloprotease (MP)-dependent down-regulation of CD30. The long-term objective of this project is to assess the role of CD30:CD153 interaction in the pathogenesis of RA. We hypothesize that, in RA patients, the increased production of pathogenic antibodies stems from the profound dysregulation of the CD30:CD153-dependent inhibitory pathway. This may result from the ability of DC-like RA synoviocytes to impair the synovial pool of CD30 suppressor T cells by eliciting rapid MP-dependent cleavage of CD30. The relevance of this phenomenon in the pathogenesis of RA is supported by the observation that RA patients display increased levels of synovial soluble CD3O that positively correlate with the levels of circulating rheumatoid factor as well as with the disease activity. The following specific aims will address the role of CD30:CD153 interaction in the pathogenesis of RA. Aim 1. Analyze the expression, requirements and function of CD30 in RA T cells, and evaluate the mechanisms by which CD30 signaling down-regulates CD154. Aim 2. Analyze the ability of CD30:CD153 interaction to inhibit Ig class switching in CD154-activated B cells, and evaluate its possible dysregulation in RA. Aim 3. Analyze the ability of CD30:CD153 interaction to inhibit the CD154-mediated activation of RA synoviocytes, and evaluate the ability of synoviocytes to reverse the inhibitory activity of CD30+ T cells. In addition to elucidating the pathogenesis of RA, the experiments outlined in this application should allow to devise new strategies aimed at reducing the production of pathogenic antibodies, including rheumatoid factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF CYTOKINES IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Tsark, Eleanor C.; City of Hope National Medical Center Duarte, CA 91010 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: Rheumatoid arthritis (RA) is an autoimmune disease characterized by infiltration of T cells and antigen presenting cells (APC) from the blood into the synovial joint. Activation of both cell types results in destruction of tissue within the joint. This tissue destruction leads to an abundance of self proteins available for uptake by phagocytic APC. Presentation of self peptide:MHC complexes by APC is believed to
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lead to activation and expansion of autoreactive T cells. The most convincing evidence implicating a role for antigen presentation in RA is the observation that inheritance of certain subtypes of the HLA-DR4 allele predisposes people to developing RA. The nature of the self peptides being presented by these DR4 subtypes is currently not known, but studies performed in animal models have provided some candidate autoantigens. The following studies are proposed: Aim 1: Determine the array of epitopes derived from candidate autoantigens expressed by normal peripheral blood APC and determine how cytokines modulate presentation of these epitopes; Aim 2: Determine the array of epitopes derived from candidate autoantigens expressed by APC obtained from RA patients and determine how cytokines modulate presentation of these epitopes; Aim 3: Determine if mature dendritic cells obtained from rheumatoid synovia display enhanced ability to process and present soluble autoantigens due to the presence of inflammatory cytokines. T cell hybridomas which recognize peptides derived from human type II collagen HCgp39 and calreticulin in the context of DR4 have been generated by immunizing human DR4 transgenic mice with these candidate autoantigens. These T cell hybridomas can then be used to study presentation of these epitopes by APC from human DR4 donors with and without rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF DPP1 AND GRANZYMES IN INFLAMMATORY ARTHRITIS Principal Investigator & Institution: Pham, Christine Tn.; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects about 1 percent of the general population worldwide. The disease is characterized by inflammation of the synovial joints leading to destruction of cartilage and bone. The initiating events and the mechanisms that perpetuate the inflammation remain obscure. Although the role of CD4+ T cells has been established, the function of cytotoxic lymphocytes in this disease has not been entirely elucidated. Some studies suggest that cytotoxic lymphocytes may decrease the incidence or suppress inflammation in murine models of arthritis. Cytotoxic lymphocytes exert their effects mainly through target cell apoptosis. One of the major mechanisms utilized by these cells to kill their targets is the granule exocytosis pathway. Activated lymphocytes contain a family of highly related serine proteases termed granzymes. Recent evidence suggests that granzymes are required for cell-mediated cytotoxicity. We recently created a mouse with a null mutation in the cysteine protease dipeptidyl peptidase I (DPPI) and showed that this enzyme is required for the activation of granzymes A and B in vivo. Furthermore, we showed that DPPI-deficient cytotoxic lymphocytes have a severe defect in their ability to induce DNA fragmentation and apoptosis from different target cells. The objective of this proposal is to evaluate the role of DPPI/granzymes in models of murine arthritis. We hypothesize that cytotoxic lymphocytes, through the action of granzymes, may have a -protective role in murine inflammatory arthritis. To explore this hypothesis, we propose the following aims: 1. We will explore the role of DPPI and granzymes in models of murine arthritis. Since there is no single animal model that recapitulate all the features of RA, we will study 3 distinct murine arthritis models that differ in the degree and type of cartilage damage [zymosaninduced arthritis (ZIA), antigen-induced arthritis (AIA), and collagen-induced arthritis (CIA)]. 2. We will explore the role of CD8+ I cells and granzymes in CIA We hypothesize that CD8+ T cells may exert a protective role in CIA, through the actions of
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granzymes. In this aim, we propose to generate chimeric animals using severe combined immunodeficient (SCID) mice. Spleen cells from arthritic mice will be depleted of CD4+ or CD8+ T cells prior to transfer into SCID mice to elucidate the specific role of T lymphocyte subsets (and granzymes) in the induction and progression of arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF FATIGUE IN RHEUMATIC DISEASES Principal Investigator & Institution: Lange, Gudrun; Associate Professor; Psychiatry; Univ of Med/Dent Nj Newark Newark, NJ 07103 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2004 Summary: (provided by applicant): Fatigue is a common complaint in rheumatic disorders and is one of the strongest predictors of physical dysfunction in patients with Fibromyalgia (FM) and other related disorders, rheumatoid arthritis (RA), osteoarthritis (OA), and systemic lupus erythematosus (SLE). However, research addressing the causes and mechanisms of fatigue is rare in rheumatic illnesses. The lack of scientific evidence focusing on the role of fatigue in rheumatic illness directly impacts on the ability of health care professionals to assess the presence, severity and trajectory of fatigue and to evaluate the relationship of fatigue with other symptoms of these disorders in order to provide appropriate treatment recommendations. Fatigue is one of the most commonly reported, yet least understood and unrelieved symptoms accompanying chronic illnesses. The primary objective of the proposed workshop is to establish a knowledge base of current information on fatigue in rheumatic illness that will be compared with the state of knowledge gained from studies of fatigue in cancer, HIV/AIDS, stroke, and MS. This process will serve to identify knowledge gaps concerning the role of fatigue in rheumatic illness. Directions for future fatigue research in rheumatic illness will be suggested incorporating research methodologies that have proven successful in other somatic disorders. To achieve these objectives, a group of renowned fatigue and sleep researchers drawn from a variety of scientific areas including neuroscience, physiology, immunology, and psychiatry/psychology, clinical practice, as well as representatives of public interest groups will be invited to attend a workshop to be held on March 18 and 19, 2004 at the Dolce Hamilton Park Conference Center in Florham Park, NJ. Presentations addressing definition, conceptualization, and assessment of fatigue in general will proceed state-of-the-art overviews of fatigue research in FM, RA, OA, SLE, cancer, HIV/AIDS, stroke, and MS, and will be followed by concentrated discussions in break-out groups. A position statement summarizing the results from this workshop will be produced at the conclusion of the meeting and disseminated via publication in a peer-reviewed journal. The collaborative and interactive nature of the proposed workshop will ensure that the recommendations generated will have a broad impact on the scientific community, and will generate collaborative, interactive research amongst scientists and clinicians with an interest in rheumatic illnesses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF SUPERANTIGENS IN TREATMENT OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Cannon, Grant W.; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001
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Summary: This project has now been completed. Twenty-three patients were enrolled at the University of Utah, with a total of 240 patients participating at twelve other sites across the nation. Although part of a multicenter trial, a specific hypothesis was tested by investigators at the University of Utah. Dr. Cannon doubted that immune complex absorption represented the mechanism by which protein A absorption exerted its therapeutic effect. An alternate hypothesis was proposed, stating that patients treated with protein A-perfused plasma developed immune responses to staphylococcal proteins leached from the column, which then altered immune responses to rheumatoid arthritis. The putative staphylococcal proteins were predicted to function as super antigens. Testing of the counter hypothesis was deemed an appropriate indication to make this a category A study by the GCRC Advisory Committee. The study has now been completed, and a preliminary analysis supports the hypothesis. A publication will be prepared describing the findings within the next year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF UBIQUITIN REGULATED F-BX07 PROTEIN IN RA Principal Investigator & Institution: Zhang, Huang-Ge G. Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): The overall goal of this proposal is to determine the biological effects of a novel F-box-containing protein (F-bx07) that we identified recently, with an emphasis on its role in the regulation of proliferation of rheumatoid synovial fibrobiasts (RASF). This goal will be achieved through three specific aims, centered on three objectives. The first objective is to determine if F-bx07 protein regulates the cell cycle of synovial fibroblasts. The second objective is to identify the protein(s) that F-bx07 targets leading to the attenuation of proliferation of RASF. The third objective is to determine if expression of F-bx07 protein is essential for prevention of the development of arthritis in vivo. The first objective is strongly supported by our initial observations that hyperproliferating RASFs lack of expression of F-bx07 mRNA, and transfection with AAVCMVF-bx07 attenuates RASFs proliferation. We will determine if inhibition of RASF proliferation of F-bx07 protein is controlled through regulation of the cell cycle. Cell cycle kinetics will be analyzed by flow cytometry analysis of cells stained with propidium iodide to determine the cell cycle stage controlled by F-bx07.1n the second aim, we will identify the molecules targeted by Fbx07 that directly and/or indirectly regulate cell cycle. Our preliminary data indicate that F-bx07 causes degradation of phosphorylated AKT and other investigators have shown that AKT participates in cell cycle regulation by controlling cell cycle kinase activity. To determine if additional cell cycle regulated proteins, especially those associated with the ubiquitin pathway are potential targets for F-bx07 degradation, the RASFs will be transfected with AAVCMVF-bx07 in the presence or absence of proteasome inhibitors and co-immunoprecipitated. Novel proteins will be identified by mass spectrometer analysis. Finally, we will validate our findings in vivo. Brdu labeling to track RASF proliferation in rheumatoid synovium organ culture, and immunohistostaining of F-bx07 and cell cycle regulated proteins including AKT will determine the biological roles of F-bx07 in vivo. Antiproliferative effects of F-bx07 protein on of RASF will be demonstrated by gene therapy in an RASF implanted SClD mouse model. The findings will have practical applications in the potential treatment of human arthritis. At a more basic level, these experiments will test the hypothesis that F-bx07 regulates synovial fibroblast proliferation and that loss of F-bx07 protein activity
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triggers synovial fibroblast hyperproliferation in RA. This will lead to a better understanding of the mechanisms underlying hyperproliferation of RASFs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SC-58635 COMPARED TO DICLOFENAC IN OSTEOARTHRITIS OR RHEUMATOID ARTHRITIS Principal Investigator & Institution: Friedman, Alan W.; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SCOR ON THE PATHOGENESIS OF RHEUMATOID ARTHRITIS Principal Investigator & Institution: Kang, Andrew H. Professor; Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-JUL-2006 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELECTIVE DISRUPTION OF TNFA SIGNALING IN MURINE CIA Principal Investigator & Institution: Scheinman, Robert I. Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2003 Summary: (provided by applicant): The inflammatory cytokine, TNF alpha, has been shown to play an important role in rheumatoid arthritis (RA) through the study of murine collagen induced arthritis (CIA). These results have propelled several TNF alpha blocking drugs into clinical use. These drugs are not universally effective and can have serious side effects. Importantly, the role of TNF alpha in RA is not fully understood. Blockade of TNF alpha signaling, both in CIA and in RA, does not stop the disease but rather slows disease progression. In the CIA model, signaling through the p55 TNF receptor (TNFRI) has been shown to mediate some TNF alpha effects however signal transduction through TNFRII has not yet been investigated. In addition, TNFRI signaling is complex. Through interactions with the adapter protein TRADD, TNFRI can activate both FADD and caspase mediated apoptosis as well as TRAF2 and RIP, leading to activation of JNK and proliferation as well as NF-KB mediated antiapoptotic and proinflammatory responses. Through interactions with the adapter protein FAN, TNFRI can activate neutral sphingomyelinase and the production of ceramide, which in turn activates a variety of signaling events. The relative importance of these signal transduction cascades for arthritis is currently unknown. TNFRI and TNFRII are present on multiple cell types. Thus it is likely that different cell types may favor different signaling pathways when activated by TNF alpha. We propose to identify specific subsets of tissues in which TNF alpha signaling contributes to the development of arthritis in the CIA system. Our strategy is to use bone marrow (BM) transplant technology to place TNFRI-'- BM into irradiated TNFR+/+ recipients or conversely, TNFRI+/+ BM into TNFRI -/- recipients. Similar experiments will be performed with TNFRII mice. By this means we can distinguish between the contribution of hematopoietic TNF alpha signaling versus non-hematopoietic TNF alpha signaling to
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CIA as well as the relative importance of TNFRI and TNFRII signaling in this process. We will then begin to dissect the signal transduction cascades mediated by TNF alpha activation of TNFRI by introducing dominant negative adapter proteins using either retroviral mediated gene transfer into hematopoietic BM stem cells or by creating transgenic mice delivering the dominant negative proteins to the synovium. In summary, these experiments will increase our understanding of how TNF alpha signaling in different cell types contributes to CIA. By extension, these data will help us understand more fully the mechanisms of action of TNF alpha blocking drugs and potentially will identify new targets for future arthritis therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SELF MANAGEMENT, EDUCATION AND OUTCOMES IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Callahan, Leigh F. Associate Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001 Summary: Low levels of formal education are associated with increased prevalence, morbidity and mortality of most common chronic diseases. Several studies suggest that formal education level may be a surrogate for behavioral/psychosocial variables, which are also independently correlated with health status and outcomes. While circumstances associated with lower levels of formal education and poor SES cannot be altered through medical intervention, certain behavioral variables may be amenable to improvement, at least in part. The set of behaviors an individual uses to cope with a chronic condition is known as self-management. Individuals with a chronic disease negotiate the specific practices in their self-management strategies based on their needs and resources. Formal education level may be a marker for the capacity of individuals with a chronic disease to develop optimal self-management strategies. The objective of this study to examine self-management strategies of individuals with rheumatoid arthritis (RA) in the context of measures of disease activity, perceived control, and formal education level vis a vis health outcomes. The objective will be approached through the following specific aims: 1) to characterize self-management in individuals with RA; 2) to examine associations between self-management and formal education level in individuals with RA; 2) to examine associations between self management and formal education level in individuals with RA; 3) to determine whether the domains and frequency of use of self-management strategies reported by individuals with RA vary over time with changes in measures of disease activity; and 4) to define the relative contribution of self-management strategies and formal education level to health care utilization and health-related quality of life over a three year period in individuals with RA. If associations between level of formal education and health status can be accounted for, at least in part, by psychological status and self- management strategies, health care providers might more effectively target patient education interventions to effect an improvement in health status. In addition, there is emerging evidence that helping patients manage not just their disease, but also common underlying needs, is cost effective. Therefore, clinicians, health care policy-makers, public health planners and voluntary health agencies could all benefit from a better understanding of possible mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SHARED EPITOPE AND RA SEVERITY: META-ANALYSIS Principal Investigator & Institution: Gorman, Jennifer D.; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 15-SEP-1977; Project End 31-DEC-2002 Summary: The shared epitope (SE) hypothesis was initially proposed to explain genetic susceptibility to rheumatoid arthritis (RA), but further study suggests that the primary role of the SE may be in the development of more severe manifestations of the disease. Despite numerous studies over the past decade, the true relationship of the SE and RA severity remains unclear. Difficulty in clarifying this relationship is likely due to differences in the populations studied: those of ethnicity, clinical factors and the particular SE allele inherited as well as the small number of patients in individual studies. In order to examine the association thoroughly, evaluation of a large, clinically and ethnically diverse population is required, and to date, no attempt has been made to initiate such a project. The goal of this proposal is to precisely define the role of the SE in severity of RA among patients with a broad range of ethnic and clinical characteristics. In order to accomplish this goal we have the following specific aim for this project: 1. To perform a meta-analysis of the association of the SE and severity of RA utilizing individual level data obtained from researchers worldwide. Because the relationship between genotype and RA severity appears to vary according to characteristics of the patients, such as ethnicity and gender, the importance of these covariates will be examined. The association will be analyzed in terms of three genetic models: presence or absence of the SE, SE dosage (0, 1, or 2 alleles), and by the specific SE genotype inherited. Severity of RA will be defined by the following outcome measures: seropositivity, presence of radiographic erosions, disease course, requirement for joint surgery, and presence of nodules or other extra- articular manifestations. This proposal of a meta-analysis with use of individual level data will allow us to more clearly define the precise relationship between the SE and RA severity and has the ability to provide genetic predictors of prognosis for RA patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNALING RHEUMATIOID ARTHRITIS
PATHWAYS
CONTROLLING
NF-KB
IN
Principal Investigator & Institution: Makarov, Sergei S.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Rheumatoid arthritis (RA) is a prototype of chronic inflammatory disease. Our preliminary studies in animal models of RA demonstrated crucial involvement of NF-kappaB in regulation of inflammation, apoptosis, and proliferation in the arthritic synovium. Thus, NF-kappaB emerges as very attractive target for therapeutic intervention in RA and other chronic inflammatory conditions. The most logical way to inhibit NF-kappaB activation is to modulate the signaling cascades which controls transcriptional activity of NF-kappaB. Two signaling cascades, the NIK/IKK and p38 MAP kinase pathways, are particularly important in regulation of NF-kappaB in RA. Our knowledge of the physiological function of these pathways is very limited, mainly due to inadequate experimental approaches. The major purpose of this proposal is to determine the physiological role of the NIK/IKK and p38 signaling pathways in activation of NF-kappaB in RA, and to assess the contribution of these pathways in major manifestations of RA, i.e. inflammation, tumor-like expansion of invasive synovium, and bone and cartilage resorption, and thus evaluate these pathways as
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targets for therapeutic intervention. We will employ gene transfer technology for dissecting the role of the NIK/IKK and p38 MAPK for therapeutic intervention. We will employ gene transfer technology for dissecting the role of the NIK/IKK and p38 MAPK pathways in NF-kappaB activation in the RA pathology. Using intraarticular (i.a.) gene transfer of dominant negative (DN) inhibitors should allow for the clear-cut interpretation of the role of these pathways in RA and will validate these pathways as targets for drug discovery. In Aim 1, we will examine the role of the NIK/IKK and p38 pathways in NF-kappaB activation, inflammatory and mitogenic responses, and apoptosis on the cellular level in synovial fibroblasts and monocytic cells in vitro. Next, we will assess the role of the NIK/IKK and p38 pathways in vivo in NF-kappaB activation, inflammation, hyperplasia, and bone and cartilage resorption in SCW arthritis in rats (AIM 2). The relevance of these data to human disease will be examined by using a SCID mice/human models of RA (Aim 3). These experiments will determine the role of NF-kappaB, and the NIK/IKK and p38 pathways in regulation of inflammation, apoptosis, and cartilage destruction in human RA synovium. One unexpected result of our preliminary studies in animal arthritis was observation that local suppression of NF-kappaB in the synovium ameliorated disease not only in treated, but also in untreated, contralateral joints. This indicates the feasibility of alleviating systemic manifestations of the disease through local treatment. Aim 4 serves to explore two putative mechanisms underlying this effect. We will examine the influence of local suppression of NF-kappaB on the balance of pro- and antiinflammatory TH1 and Th2 subsets in circulating T cells, and in neurogenic mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP IN CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS Principal Investigator & Institution: Labyak, Susan E.; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Approximately 285,000 of America's children have been diagnosed with arthritis, and juvenile rheumatoid arthritis (JRA) is the most prevalent form. Children with JRA, regardless of disease severity, report poor sleep quality, excessive daytime sleepiness, anxiety, and altered mood. Adequate sleep is essential for health and normal growth and development in children. Insufficient sleep in healthy children has been associated with hyperactivity, decreased attention span, distractibility, impulsivity, excessive daytime sleepiness, poor neurobehavioral performance, decrements in school performance, and increased school absenteeism. Disturbed sleep in children with JRA is likely to have similar negative impact on the child's behavior, mood, school performance, ability to carry out daily physical and social activities, as well as disease symptom (pain, stiffness, fatigue) severity. Sleep quality may be an important predictor of symptom severity, school performance, and how well children with JRA adjust to living with this chronic illness. In our preliminary studies, we have begun to document the extent of disturbed sleep by self-report and behavioral and physiological indicators in a small sample of children with JRA. These data show for the first time that sleep is most disrupted during periods when inflammation and joint swelling are most acute, yet children complain of poor sleep quality and excessive daytime sleepiness even during periods of disease remission. The extent of disrupted sleep and its impact on daytime functioning has not been studied in children with JRA. The proposed study builds on our pilot studies findings and is unique in that it will use a within-subject, repeated-measures design to determine the extent of poor nighttime
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sleep and evaluate the impact of poor sleep on daytime sleepiness, neurobehavioral performance, academic performance, and emotional/affective indicators during both periods of arthritic flare and disease remission. The results of this study will provide key information about sleep quality and daytime functioning in children with JRA; thus setting directions for the development of clinical therapies to enhance sleep quality during periods of arthritic flare as well as disease remission as different treatment strategies likely will be required. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP REGULATION AND TUMOR NECROSIS FACTOR Principal Investigator & Institution: Krueger, James M. Professor of Neurobiology; Vet & Comp Anat/Pharm/Physiol; Washington State University 423 Neill Hall Pullman, WA 99164 Timing: Fiscal Year 2001; Project Start 01-AUG-1993; Project End 31-JUL-2005 Summary: (provided by applicant): Sleep is of central importance to neurobiology because to understand how the brain works, we will have to decipher the mechanisms and functions of sleep. The function(s) of sleep remain unknown and the humoral and neural mechanisms of sleep are incompletely understood. Most people intuitively recognize that sleep increases after sleep loss or during the course of an infection. There is much evidence that those sleep responses, as well as physiological sleep, are regulated, in part, by humoral mechanisms. We hypothesize that tumor necrosis factor alpha (TNF-alpha) is one of the key substances in sleep regulation. This hypothesis is based on studies showing: 1) TNF-alpha induces non-rapid eye movement sleep (NREMS); 2) inhibition of TNF-alpha inhibits spontaneous sleep and sleep responses induced by sleep loss or bacterial products; 3) TNF mRNA and TNF brain levels correlate with sleep propensity; 4) in humans, circulating TNF levels correlate with electroencephalogram slow-wave activity and increase after sleep loss or during several pathologies with associated fatigue, e.g., sleep apnea, rheumatoid arthritis, preeclampsia, multiple sclerosis. The proposed experiments seek to understand in mechanistic detail how TNF-alpha is involved in sleep regulation. We will determine whether blocking TNF-alpha or TNF-alpha production centrally attenuates systemic TNF-alpha-induced sleep responses; preliminary data show that vagotomy attenuates systemic TNF-alpha-induced NREMS (Specific Aim #1). We will investigate TNF-alpha regulation of NREMS within specific TNF-active sites in brain (Specific Aim #2). Preliminary data indicate that microinjection of TNF-alpha into the preoptic area enhances NREMS, whereas microinjection of an inhibitor of TNF-alpha reduces NREMS. Pharmacologic blockage of prostaglandins, adenosine, and interleukin-1, and sleep manipulation using sleep deprivation and acute mild increases in ambient temperature to enhance sleep, will be combined with microinjections of TNF-alpha or TNF-alpha inhibitors. We will also use gene arrays to determine the time course of sleep-sensitive changes in brain for TNF and TNF superfamily member mRNAs. Anticipated results will provide molecular-mechanistic advances to understand sleep regulation as well as aid our general understanding of cytokine regulation in the brain. We anticipate that results will be directly relevant to therapeutics, e.g., a TNF soluble receptor has already been shown to reduce fatigue associated with rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRESS AND ADAPTATION TO RHEUMATOID ARTHRITIS Principal Investigator & Institution: Zautra, Alex J. Professor and Program Director; Psychology; Arizona State University P.O. Box 873503 Tempe, AZ 852873503
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Timing: Fiscal Year 2001; Project Start 10-APR-1994; Project End 31-MAY-2005 Summary: Description (adapted from investigator's abstract): This research is designed to determine the extent to which variations in cognitive behavior therapy reduce disease activity and improve the mental health of older adults with rheumatoid arthritis (RA). The study combines field assessments, laboratory tests of stress reactivity and clinical evaluations of the mental and physical health of subjects in a longitudinal design. After pre-testing, 210 RA patients will be randomly selected in one of three treatments: Cognitive-Behavior Therapy for Pain (CBT-P), Cognitive-Behavior Therapy for Depression (CBT-D) or Education Group only (EG), which serves as a control. The distinction between pain and depression as foci of CBT in RA is supported by previously funded research by the investigator on interpersonal stress and disease activity in persons with arthritis. Illness severity, depressive symptoms and interpersonal difficulties are expected to predict psychological and physiologic stress responses in participants. Stress reactivity measures are expected to predict the course of illness over time. Those receiving CBT-D are expected to show the greatest improvement in physical functioning, mental health and disease activity. Successful treatment is expected to alter stress responses, leading to better physical and mental health over time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL BIOLOGY OF TYROSINE KINASE REGULATION Principal Investigator & Institution: Horita, David A. Biochemistry; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The Src-family of nonreceptor kinases includes eight distinct proteins identified in humans. These proteins play wide-ranging roles in signal transduction in a variety of cell types, and are implicated in numerous diseases including cancer, HIV infection, rheumatoid arthritis, and Type I diabetes (DM1). Inhibition of Hck prevents onset of diabetes in animal models, suggesting this protein as a target for anti- DM1 drug development. The plethora of human tyrosine kinases makes design of high-specificity inhibitors difficult. The long term objective of this project is to develop a comprehensive, detailed understanding of the structural basis of Hck regulation which will be of use in the design of highly specific Hck inhibitors. Such drugs should have broad applicability in the treatment of rheumatoid arthritis and DM1. The specific aims of this pilot project are (1) to establish a bacterial expression system to produce Hck suitable for analysis by solution-state NMR spectroscopy and (2) to initiate NMR studies using these molecules. Specific aim 1 entails stable-isotope labeling of recombinant Hck and in vitro phosphorylation. Specific aim 2 entails assignment of 1H, 13C, and 15N resonance of Hck and collection and analysis of backbone 15N relaxation data. These studies will establish the feasibility of comprehensive analysis of tyrosine kinase structure and dynamics using NMR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURAL STUDIES OF IMMUNOPHILINS AND RELATED PROTEINS Principal Investigator & Institution: Clardy, Jon C. Professor; Chemistry and Chemical Biology; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2001; Project Start 10-JUL-1992; Project End 31-DEC-2003
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Summary: Immunophilins and related proteins participate in many fundamental biological processes, and this project's overall goal is analyzing these processes in structural terms. In addition to providing a basic structural understanding of these important proteins, the project has practical implications for prevent graft versus. host disease in transplant patients, alleviating autoimmune diseases such as rheumatoid arthritis and insulin- dependent diabetes, and developing small molecules for regulated gene therapy. Separate projects include: Structures of the large immunophilins FKBP51 and FKB952 along with their partners in the steroid receptor complex Hip and Hop. Structure of FRAP, a member of the ATM family of proteins involved in cell cycle checkpoints and DNA repair. Structure of dihydroorotate dehydrogenase, the protein target of the rheumatoid arthritis drug leflunomide (Arava) and the anti- cancer agent brequinar. Structure of the dimerizing agents based on FKBP12-rapamycin- FRB that are clinically useful in small molecule regulated gene therapy. Structures such as fyn SH2pYEEI/FK506-FKBP52 that illustrate the concept of using borrowed endogenous proteins to moderate the binding of hybrid small molecules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDY ADMINISTERING MYCOPHENOLATE MOFETIL FOR ACTIVE RHEUMATOID ARTHRITIS Principal Investigator & Institution: Merkel, Peter A.; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001 Summary: This study is an extension of the double-blind, randomized, parallel group, multicenter comparison of the efficacy and safety of Mycophenolate Mofetil and placebo in patients with active Rheumatoid Arthritis. The design is an open label trial of MMF therapy in RA patients for a minimum of 6 months and will have a duration of approximately 1 year, evaluating the long-term safety profile. Five patients are anticipated to participate in this extension study. Patients who are eligible to be included in this study are those who have completed the 6 month blinded treatment protocol and continuing abstinence of contradictions or exclusion factors relating to safety as defined in the protocol of the blinded study. Concurrent Glucocorticoids (<=10mg/d Prednisolone or equivalent) &/or NSAID use will be allowed if the patient has been treated with them through out the blinded study. Patients will begin the study at the last visit of the blinded study & MMF will be dispensed. They will return 2 weeks and 4 weeks later and then for once a month visits for the following two months. Later visits will take place every 6 weeks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTHRITIS
SUBCUTANEOUS
RHUIL10
THERAPY
FOR
RHEUMATOID
Principal Investigator & Institution: St Clair, Eugene W.; Duke University Durham, NC 27706 Timing: Fiscal Year 2001 Summary: Purpose: The purpose of the present study is to determine the safety and tolerability and potential clinical efficacy of subcutaneous doses of recombinant human IL-10 (rHuIL-10) in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease of unknown etiology. It is characterized by synovial inflammation with frequent progression to articular cartilage and bone destruction. The synovial inflammatory response in RA consists predominately of T lymphocytes, mostly T helper
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cells (Th), with fewer numbers of macrophages and B lymphocytes. RA is widely believed to be a Th1-mediated disease, although the data to support this hypothesis is circumstantial. For example, Th1 cells are associated with cellular immune responses, which seems to fit with the characteristics of rheumatoid joint inflammation, and T cell clones isolated from synovial tissue of RA patients most often secrete Th1 cytokines (such as interferon). IL-10, a cytokine produced by Th2 cells and macrophages, has primarily immunosuppressive and anti-inflammatory properties. The inhibitory effects of IL-10 have been observed in animal models of arthritis where treatment with this cytokine can ameliorate joint inflammation. Methods: The study is a phase II, multicenter, double-blind, placebo-controlled, clinical trial of daily (4 5g/d, 8 5g/d, or placebo) or three times week (8 5g/d, 20 5g/d or placebo) subcutaneous rHuIL-10 therapy. The dosing period is twelve weeks for the randomized phase and an additional 12 weeks for the extension study. The study was amended to include an open label portion with a total of 80 weeks of treatment. The main outcomes are the frequency and severity of adverse effects and the American College of Rheumatology Core Disease Measures. Results: The study is ongoing, but enrollment has been completed. A total of 18 patients were screened with 10 completing the initial portion of the protocol. 8 patients moved to the extension, with 6 continuing into the open label portion of the study. Currently, 3 patients remain active in the open label portion of the protocol with 2 patients sheduled for early termination and final follow- up visits during the month or December, 1998. Our site enrolled 7 Caucasian females, 2 Caucasian males, and 1 AfroAmerican male. There have been 8 serious adverse events involving patients who were hospitalized and with problems that were possibly related to the study drug. They were as follows: 1) Diverticulitis and urinary tract infection; 2) Supraventricular tachycardia; 3) Breast Cancer; 4) Allergic interstitial nephritis; 5) Demyelinating disease with left sided numbness 6) RA flare with pneumonia; 7) Death following cardio-vascular collapse; 8) Nausea, vomiting and diarrhea resulting in dehydration , electrolyte imbalance and hypotension. The results of the phase I study showed that the study drug was well-tolerated and did not cause any serious adverse reactions. Platelet counts dropped significantly in several patients receiving the two highest doses of IL-10, with platelet counts in 2 cases dropping below 100,000/mm3. There were no bleeding complications, and the thrombocytopenia was quickly reversible upon stopping the study. No responders were noted in the two lowest dosage cohorts, but in the 5 5g/d dosage cohort, 3 of 8 patients were classified as responders. These preliminary results suggested that IL-10 therapy may offer some clinical benefits to patients with RA without causing major toxicity. Significance: Insights into whether RA is a Th1-driven response in RA may be obtained by examining the treatment and biological effects of cytokines that downregulate Th1 responses. The results of the phase I study are preliminary and do not yet provide sufficient evidence to prove or refute the Th1 hypothesis. Furthermore, the results of this small trial and future studies may be difficult to interpret because of the knowledge that cytokines are pleiotropic in their actions and may exhibit unique synergistic effects in the company of other cytokines. For example, IL-10 inhibits cytokine production by Th1 cells, inhibition of antigen presentation and cytokine production by macrophages and monocytes, and enhances of B-cell proliferation and antibody secretion. In addition, redundant cytokine and other inflammatory pathways exist in vivo that may compensate for the lack or excess of a particular cytokine. Future plans: A phase I study of IL-10 and methotrexate is ongoing and a larger phase III study of IL-10 is planned for 1999. The projected endpoint for the open label portion of the phase II trial is February/March, 2000. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SURVIVAL MODELS FOR MAPPING GENES FOR COMPLEX DISEASES Principal Investigator & Institution: Li, Hongzhe; Associate Professor; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, CA 95616 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2005 Summary: (provided by applicant): The long term objective of this project is to develop powerful and computationally efficient statistical methods of identifying genes underlying complex genetic diseases in humans. The specific aim of this project is to continue to develop survival models to incorporate age of onset data, environmental covariates information, gene-environment interactions, and multiple disease loci into family-based association analysis, joint linkage and linkage disequilibrium analyses, and multipoint multi-trait-locus linkage analysis of complex human diseases. The proposed methods build on our current methods and hinge on novel integration of methods in multivariate survival analysis and methods in modern human genetics. The focus will be on the development of survival models for: (1) incorporating age of onset and environmental risk factors into genetic association study using a linkage disequlibrium based Cox model for family data of any size; (2) joint analysis of linkage and linkage disequilibrium for age of onset data based on nuclear families; (3) for multipoint multitrait-locus linkage tests that can incorporate age of onset and environmental covariates data using the additive genetic frailty model. The project will also investigate the power and efficiencies of these methods, and compare them with existing methods. In addition, this project will develop practical and feasible computer programs in order to implement the proposed methods, to evaluate the performance of these methods through extensive simulations and application to real data on HLA-associated diseases, including type 1 diabetes, rheumatoid arthritis, celiac disease, narcolepsy, and ankylosing spondylitis. The work proposed here will contribute both statistical methodology to mapping genes for complex diseases and multivariate survival analysis, offer insight into each of the clinical areas represented by the various data sets to evaluate these new methods, and facilitate final identification of genes involved in these complex diseases. All programs developed under this grant and detailed documentations will be made available free-of-charge to interested researchers via the World Wide Web. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNOVIAL CADHERIN IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Brenner, Michael B. Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant) Cadherins are integral membrane adhesion proteins that mediate homophilic adhesion (bind to cadherins of the same type) on cells within a tissue. During development they mediate the sorting of cells into tissues and in adults the integrity and architecture of tissues. Cadherin expression and signaling are also known to participate in regulating cell proliferation, migration and invasion. For example, loss of E-cadherin (E-cad) expression that mediates integrity of the epithelium, is associated with epithelial cell progression to malignancy, invasion and metastases. Normal synovium is a tissue of a few cells thick composed of Type A, monocyte-like synoviocytes (MLS) and Type B, fibroblast-like synoviocytes (FLS). Yet the synovial lining is neither a true epithelium nor endothelium as it lacks a basement membrane. We hypothesize that a distinct cadherin might be expressed on synoviocytes and play a
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role in making the synovium a tissue. We identified cadherin-11 (cad-11) expressed by the type B FLS, but not by fibroblasts in skin, gut, or various other tissues. Here we show preliminary data that cad-11 influences the proliferation, adhesion and cytoskeletal organization of FLS. Thus, we propose to define the role of cad-11 in influencing the proliferation of FLS cultured in the presence of cad-11 expressing cells or plate-bound cad-11 fusion proteins coated on plastic wells. Effects on the major signaling pathways affecting FLS activation, proliferation, apoptosis, migration and invasion will be determined, since these features bear relevance to the abnormal proliferation and invasion characteristics of synovial cells in the rheumatoid pannus. We have previously described that lymphocytes bind E-cadherin via the alphaEbeta7 leukocyte integrin (a heterophilic interaction). Here, we propose to identify the lymphocyte receptor that mediates adhesion to cad-11, as it may play an important role in lymphocyte adhesion and localization in the inflamed synovium. Finally, we have confirmed expression of cad-11 in a mouse model of synovitis and will administer anticad-11 mAb and cad-11-Fc to assess the potential value of cad-11 as a therapeutic target in inflammatory synovitis. Together, these studies are likely to yield new insights into the biology of synoviocytes and identify a new biotherapeutic target (the synovial cadherin) having potential relevance to rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNOVIOCYTE DESTRUCTION
RHO-TYPE
GTPASES
IN
CARTILAGE
Principal Investigator & Institution: Crofford, Leslie J. Associate Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 05-MAY-2000; Project End 30-APR-2003 Summary: (abstract taken from application): Loss of articular cartilage in rheumatoid arthritis (RA) is associated with the normal migration of synoviocytes and increased secretion of matrix metalloproteinases (MMPs). Growth, adherence, and migration, as well as signal transduction pathways known to induce transcription of MMPs, are mediated by the Rho-type GTPases. The Ras-related GTPases, RhoA, RacI, and Cdc42, interact with the actin cytoskeleton to alter morphology. They can be activated by growth factors (e.g., PDGF), cytokines (e.g., IL-lb and TNF-a and integrins. In addition, activation of GTPases leads to alteration of downstream signal transduction pathways that ultimately induce gene transcription. The general hypothesis of this proposal is that rheumatoid fibroblast-like synoviocytes (FLS) mediate cartilage destruction that is dependent on Rho-type GTPases. Specifically, we hypothesize that activation of the Rho-type GTPases affects the physical interaction between synoviocytes and articular cartilage. In addition, GTPase activation triggers a signal transduction cascade resulting in increased production of MMPs that contribute to loss of cartilage matrix in RA. In this exploratory/developmental proposal, we will use a retro viral vector system to overexpress constitutively active and dominant negative forms of the Rho-type GTPases, RhoA, RacI, and Cdc42 with polycistronic expression of enhanced green fluorescent protein. We will standardize methods for producing articular cartilage discs, both vital and devitalized, and refine our methods to assay for loss of extracellular matrix in coculture. We will develop the methods necessary to assess changes in morphology and migration of untreated, PDGF-stimulated, and IL-lB or TNF-alpha-stimulated FLS during co-culture with articular cartilage using conventional and video microscopy. We will determine the basal, PDGF-stimulated, and IL-lB or TNF-alpha- stimulated activity of the Rho-type GTPases in unmodified rheumatoid FLS. Ultimately, we will determine
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the effects of the Rho-type GTPases on synoviocyte adherence to and migration over articular cartilage, production of MMPs, and destruction of the cartilage matrix. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNOVIUM AS AN IMMUNE UNDERPRIVILEGED SITE Principal Investigator & Institution: Kipps, Thomas J. Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001 Summary: Cognate interactions between T cells and antigen presenting cells (APCs) involve a variety of accessory and adhesion molecules and cytokines that pattern the response to the presented antigens. In addition, expression of certain accessory molecules, such as Fas (CD95) and Fas-ligand, are essential for proper immune clearance of activated cells. We have found that the affected joints of patients with wellestablished rheumatoid arthritis (RA) represent "immune underprivileged sites" that harbor activated mononuclear cells that constitutively over-express stimulatory immune accessory molecules and cytokines. Furthermore, we recently have found evidence for defective clearance of such cells resulting from an acquired deficiency in expression of functional Fas-ligand in the diseased synovium. This defect may result from impaired expression of Fas-ligand mRNA and/or rapid proteolysis of Fas-ligand protein. Finally, we hypothesize that strategies aimed at reversing his acquired deficiency and/or reducing the expression of co-stimulatory immune accessory molecules will ameliorate the established phase of this disease. Accordingly, this proposal has the following specific aims: 1) examine the induction-kinetics of Fas-Ligand (Fas-L) mRNA and surface protein expression by blood and synovial lymphocytes of persons with RA and normal controls; 2) examine the stability of native Fas-L and Fas-L deletion mutants lacking the metalloproteinase cleavage site(s) under conditions within diseased joints of persons with RA; 3) generate and test viral vectors encoding native or truncated Fas-L, IL-10, or IL-13; and 4) examine whether vectors encoding native or truncated Fas-L, IL10, and/or IL-13 can ameliorate pathology in experimental animals induced to develop arthritis. Through this work we may develop effective new strategies for immune gene therapy of patients with established RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNTHESIS/ ACTIVITY OF N-AMINOTETRAHYDROPYRIDINES Principal Investigator & Institution: Redda, Kinfe Ken. Professor of Medicinal Chemistry; Florida Agricultural and Mechanical Univ Tallahassee, FL 32307 Timing: Fiscal Year 2001; Project Start 05-JUN-2000; Project End 30-APR-2005 Summary: The primary objective is the design, synthesis and pharmacological evaluation of novel and medicinally important N-amino-1,2,3,6- tetrahydropyridine derivatives. We reported the synthesis of novel N- iminopyridium ylides using the method employed by Tamura and modified in our laboratory. Sodium borohydride reduction of the ylides afforded the stable N-amino-1, 2,3,6-tetrahydropyridines in good yields. We also recently reported preliminary pharmacological test results of a few tetrahydropyridines that exhibited analgesic and anti-inflammatory activities with no observed toxicity, even at very high dose levels. Our earlier work provides the basis for new and exciting studies so that a series of compounds related to the most active analogs could be prepared, and retested and the octanol-water partition coefficient determined. Once sufficient data are accumulated, the compounds prepared will be subjected to structure activity analysis to study the electronic, steric and lipophilic
122 Rheumatoid Arthritis
effects of substituents. The physical and pharmacologic data obtained in this study will then be used to design drugs with more beneficial biological activity. The primary focus of the pharmacological studies will be to develop and easily synthesize effective and safe non- steroidal anti-inflammatory agents for the treatment of rheumatic diseases, including rheumatoid arthritis, osteoarthritis, gout and rheumatic fever. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TARGETED DEGRADATION OF PKR MRNA WITH 2-5A ANTISENSE Principal Investigator & Institution: Xu, Zan; Ridgeway Biosystems, Inc. 9500 Euclid Ave, Nd-50 Cleveland, OH 44195 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-AUG-2003 Summary: (provided by applicant): Inflammatory diseases represent increasing health care cost to American people. For many chronic inflammatory diseases (asthma, rheumatoid arthritis, bowel inflammatory diseases, etc.), there are no effective treatment. With the increase in the aging population of American society, this problem becomes aggravating. Targeted degradation of important factors (cytokines, cytokine receptors and intracellular mediators) participating in the inflammation signaling is a cost-effective strategy to develop an anti-inflammatory therapeutic measure. PKR is emerging as an important mediator for inflammatory process by transducing signaling activation of NF-kappa B or p38 to activate gene transcription of a number of inflammatory cytokines. Therefore, disruption of PKR activity is a particular attractive means of treating inflammatory diseases. The advantage of selecting PKR as a target also resides in that PKR is nonessential protein for cell survival compared with other targets (TNF-alpha, NF-kappa B, p38, etc.) which are vital for cell survival. Disruption of their activities may lead to undesirable and unexpected side effects. RBI is developing a novel class of chimerical oligonucleotides for use in antisense therapeutic strategies. This chimeras are comprised of an antisense component, which directs the compound to the complementary PKR sequences, and an activator moiety, 2',5'-oligoadenylate (2-5A) that serves to activate a cellular enzyme, ribonuclease L (RNase L), which cleaves the target RNA. Preliminary results demonstrated that 2-5A anti-PKR chimera can efficiently degrade PKR and inhibit PKR activation. The goal of this proposal is to progress this compound toward commercialization by obtaining a lead chimera compound with affinity to both human and murine PKR mRNA, and investigating the anti-inflammatory activity of the lead compound. If successful, the 2-5A anti-PKR compound will have a potential application to the treatment of chronic inflammatory diseases including rheumatoid arthritis, Crohn's diseases etc. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TCR LIGANDS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Allen, Paul M. Assistant Professor; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2001 Summary: Susceptibility to autoimmune diseases has been directly linked to the major histocompatibility complex (MHC); however, the role the MHC gene products play has not been ascertained. We propose to utilize a recently described murine model of rheumatoid arthritis (RA) to investigate the relationships between self-peptide recognition, alloreactivity, and autoimmunity. The basis for this model is the alloreactivity of a T cell, R28, specific for the RNase (41-61)/I-Ak determinant to the I-
Studies 123
Ag7 molecule. R28 TCR transgenic mice (KRN) when crossed to the NOD strain exhibited pronounced joint inflammation. The KRN x NOD mice share most of the major clinical, histological and immunological features of human rheumatoid arthritis. The 100% disease incidence and the early and reproducible time of onset make this a very attractive and powerful model. In the studies proposed in aim I, we will identify using peptide libraries an allomimotope peptide, which can stimulate the KRN T cells. This recognition will then be compared and contrasted to that of RNase (41-61)/I-Ak. These studies will provide a structural definition of the different ligands recognized by KRN T cells and insights into what type of recognition events are involved in autoreactivity. In aim II we propose to test in vivo the ability of altered peptide ligands to block the induction and development of RA. We will also involve directly visualizing in vivo the location and function of the autoreactive T cells. These in vivo studies will establish the potential of altered peptide ligands to treat RA. In aim III, we propose to identify what properties of the target ligands are necessary for disease induction. These studies will involve a second alloligand of the KRN T cells, I-AkA65, which differs from the I-Ag7 molecule in several biochemical and functional properties. Overall, these proposed studies will provide important new insights into the relationship between the T cell recognition of antigen and the development of autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TH-1 BIAS IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Davis, Laurie S. Associate Professor in Research; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 24-SEP-1999; Project End 31-AUG-2004 Summary: Rheumatoid arthritis is a chronic systemic disease characterized by persistent intense immunologic activity. Recent data have suggested that CD4+ T cells play an essential role in propagating rheumatoid inflammation. Moreover, the data suggest that one abnormality in rheumatoid arthritis is the biased differentiation of IFN-gamma producing Th1 like memory T cells within the synovial compartment. Although synovial T cells are enriched in mature CD4+ CD27- T cells, they contain few, if any, IL-4 producing Th2-like memory cells. This suggests that rheumatoid inflammation might be characterized by an abnormality in the differentiation of IL-4 producing Th2-like cells such that there is persistent unregulated activity of IFN-gamma producing Th1-like memory cells. The proposed experiments will test this hypothesis. In addition, experiments will be carried out to delineate the regulatory events controlling the differentiation of Th l-like and Th2-like cells in patients with rheumatoid arthritis, determine whether abnormalities in the differentiation pathways of these effector T cell subsets are found in patients with rheumatoid arthritis, investigate the impact of synovial influences on these differentiative pathways, and determine whether unique clones of T cells differentiate into cytokine- producing Th1-like memory cells in the rheumatoid synovium. Finally, regulation of the differentiation of Th1 and Th2-like effector cells will be directly analyzed in vivo using rheumatoid synovial tissue engrafted into SCID mice. The specific aims will be: 1) to examine the capacity of CD4+ T cells from patients with RA to differentiate into IFN-gamma or IL-4 producing Th effector cells; 2) to determine whether features of the rheumatoid synovium influence the development of Th effector cells; and finally 3) to utilize an in vivo model of rheumatoid arthritis, the RA-SCID mouse, to examine the influences on the development of Th effector cells directly. It is anticipated that the information obtained should provide important new insights into the regulatory influences on the differentiation of CD4+ memory effector cells in man.
124 Rheumatoid Arthritis
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF ANGIOPOIETIN-1 IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Oettgen, J Peter. Assistant Professor; Beth Israel Deaconess Medical Center St 1005 Boston, MA 02215 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Angiogenesis is a critical component of the inflammation associated with rheumatoid arthritis (RA). The longterm goals of the proposed studies are to understand the molecular mechanisms underlying angiogenesis in RA and thereby identify novel therapeutic approaches to treating inflammatory arthritis. Angiogenesis is a complex, multistep process that eventually leads to the development of mature blood vessels. Several angiogenic growth factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have been identified within the rheumatoid synovium, all of which promote the early steps of angiogenesis. Recently, a novel angiogenic factor, Angiopoietin-1(Ang-1) was identified, that has the unique properties of facilitating the later stages of angiogenesis. We have determined that Ang-1 is expressed in synovial fibroblasts derived from patients with RA. Furthermore, proinflammatory cytokines can markedly upregulate the expression of Ang-1 in these cells and induce Ang-1 in other cell types found in the rheumatoid synovium including monocytes and chondrocytes. In addition to its role in promoting vessel maturation Ang-1 is a potent chemoattractant. The strong expression of Ang-1 in synovial fibroblasts may facilitate the migration of endothelial cells to the growing pannus. The molecular mechanisms by which Ang-1 mediates its effects in endothelial cells are poorly understood. We have also determined that the Ets factor NERF2 is induced by Ang- 1 in endothelial cells suggesting that NERF2 is a transcriptional regulator of Ang-1 mediated effects. The hypothesis for this proposal is that Ang-1 is one of the critical factors required for the angiogenic response in rheumatoid arthritis. The goals of this grant application are to define the biological role of Ang- 1 in promoting the angiogenic component of inflammatory arthritis, to further define the biological role of NERF2 as a transcriptional mediator of Ang- 1, and examine the therapeutic potential of blocking Ang- 1 during the development of inflammatory arthritis. Thus the Specific Aims are to determine: 1. What is the biological role of Ang-1 in inflammatory arthritis? 2. What is the role of the Ets transcription factor NERF2, in mediating the biological effects of Ang-1? 3. What is the therapeutic effect of blocking the function of Ang-1 in inflammatory arthritis? The approaches that will be used to address these questions include immunohistochemistry, in situ hybridization, the examination of synovial tissue samples from patients with RA and animals with collagen induced arthritis, adenoviral and retroviral gene delivery methods, assays of endothelial function, and flow cytometry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF MCL-1 IN THE MACROPHAGES AND RA Principal Investigator & Institution: Pope, Richard M. Professor; Northwestern University Office of Sponsored Programs Chicago, IL 60611
Medicine;
Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Monocytes/macrophages are vital for host-immune responses and have been implicated in the pathogenesis of rheumatoid arthritis (RA). We demonstrated that PI3K/Akt-1-dependent Mcl-1 expression is vital for macrophage survival. Suppression of PI3K/Akt reduced Mcl-1 expression, resulting in apoptosis
Studies 125
mediated through the mitochondrial pathway. Forced downregulation of Mcl-1 through antisense oligonucleotides also induced apoptosis, demonstrating that Mcl-1 is essential for macrophage viability. Further, our preliminary data suggested that Mcl-1 may also be regulated by the JAK/STAT pathway in human macrophages. Therefore, we propose to determine the mechanisms by which the PI3K/Akt and JAK/STAT3 pathways contribute to the regulation of Mcl-1 in macrophages. Additionally, we will identify the mechanism by which Mcl-1 protects macrophages by examining the interaction of Mcl-1 with pro-apoptotic molecules, such as Bax in macrophages to delineate the mechanism of mitochondrial dysfunction that occurs following Mcl-1 ablation. Our preliminary data suggests that Mcl-1 may be important in the in maintaining the viability of RA synovial macrophages. Additionally, our preliminary data has revealed that in vitro, Mcl-1 was highly expressed in RA, compared to osteoarthritis (OA), synovial fibroblasts. Mcl-1 was also strongly expressed in the synovium of rats with adjuvant-induced arthritis (AIA). Therefore, we propose to characterize the expression and function of Mcl-1 in the RA joint, examining macrophages and synovial fibroblasts. We propose to determine if the forced downregulation of Mcl-1 will ameliorate experimental arthritis, which would indicate that Mcl-1 is a contributor to the initiation and/or progression of arthritis. Thus, this proposal will delineate the mechanisms regulating the expression and the novel functions of Mcl-1 in macrophages. Further studies are proposed to delineate potential cell type-specific differences between macrophages and normal, osteoarthritis and rheumatoid arthritis synovial fibroblasts. These experiments will provide new and important information concerning the novel role of Mcl-1, which may provide insights that will lead to the development of improved therapy for patients with RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THERAFECTIN COMPARED TO PLACEBO IN RHEUMATOID ARTHRITIS WITHDRAWN FROM NSAID Principal Investigator & Institution: Arkfeld, Daniel; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THREE DOSES RHEUMATOID ARTHRITIS
OF
MELOXICAM
W/
DICLOFENAC
FOR
Principal Investigator & Institution: Dooley, Mary A. Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TIMED RADIOTHERAPY
BIORESORBABLE
Y
90
MICROSPHERES
FOR
Principal Investigator & Institution: Peng, Yongren B. Sr. Res. Scientist, Vp; Xl Sci-Tech, Inc. 3100 George Washington Way, Ste 135 Richland, WA 99352 Timing: Fiscal Year 2000; Project Start 30-SEP-1997; Project End 31-DEC-2003 Summary: Timed-bioresorbable microspheres are being investigated as a vehicle for delivery of radioisotopes, particularly, Y-90 for localized radiotherapy. Microspheres of
126 Rheumatoid Arthritis
several calcium phosphate glasses prepared in Phase I have been shown to retain 99.0 to 99.9% of yttrium in vitro. They are non-toxic and bioresorbable. These microspheres must maintain similar structural integrity and yttrium release characteristics in vivo before they are clinically useful, since leakage of radioactivity from injection site reduces therapeutic efficacy, induces undesirable damage to normal tissues, and increases the risk of side effects and secondary neoplasia. Characterizing the release of Y-90 in vivo and identifying the relationship between in vitro and in vivo bioresorption rates will provide valuable input for glass composition optimization, and will set the criteria for bioresorption control through nano-scale chemistry. A team of distinguished collaborators gas been formed to lead in the safety and efficacy evaluations of using timed- bioresorbable Y-90 microspheres for treating solid tumors, arthritic joints, etc. Animal experiments are designed to address a variety of safety issues and adequate efficacy studies are also proposed. XL Sci-Tech expects to produce pilot quantities of timed-bioresorbable Y-90 microspheres that are safe for clinical investigations by the conclusion of the Phase II study. PROPOSED COMMERCIAL APPLICATIONS: Timedbioresorbable Y-90 microspheres will deliver highly localized beta radiation without risk of activity leakage. These microspheres are ideal for direct intratumoral injection in treatment of cancers of liver, pancreas, etc., and radiation synovectomy of rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TIMP ENGINEERING AND APPLICATION TO ARTHRITIS Principal Investigator & Institution: Brew, Keith; Professor; Biomedical Sciences; Florida Atlantic University Boca Raton, FL 33431 Timing: Fiscal Year 2003; Project Start 01-SEP-1991; Project End 31-MAR-2008 Summary: (provided by applicant): The matrix metalloproteinases (MMPs) are zinc metalloproteinases that degrade components of the extracellular matrix. They play major roles in diseases including arthritis, cancer and atherosclerosis. The activities of MMPs are regulated by endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs)-1, to -4. Our long-range goals are to understand how TIMPs inhibit MMPs and to use this information to engineer variant TIMPs that selectively inhibit individual or chosen groups of metalloproteinases. These targeted TIMPs will be tested for efficacy in alleviating the progression of diseases associated with increased degradation of the extracellular matrix. Our recent finding that TIMP-3 is a potent inhibitor of two aggrecanases (ADAMTS-4 and ADAMTS-5), key enzymes in the degradation of the cartilage proteoglycan, aggrecan, leads us to further investigate and test TIMP-3, and other TIMP variants, as inhibitors for preventing the progression of arthritis. To achieve these goals we will elucidate the structural basis of TIMP specificity for aggrecanases and MMPs and engineer TIMPs that are targeted for metalloproteinases involved in cartilage degradation. These inhibitors will be tested for effectiveness in ex vivo and in vivo models of rheumatoid arthritis (RA) and osteoarthritis (OA). The Specific Aims are: (1) to investigate the mechanism of inhibition of aggrecanases by TIMP-3 and generate specific inhibitors of these enzymes; (2) to produce TIMP variants that selectively inhibit collagenases (MMP-1 and -13), gelatinase A (MMP-2), or MT1-MMP; (3) identify and characterize low-molecular weight peptide inhibitors employing nontoxic variants of sarafotoxin, an analogue of the unique inhibitory region of TIMPs; (4) characterize the structural and physical basis of strong and specific metalloproteinase binding in TIMPs; (5) test recombinant TIMP-3 and other wild-type and variant TIMPs for their ability to prevent cartilage breakdown using the cartilage explant system; (6) test the efficacy of TIMP-3 and TIMP variants as potential blockers of cartilage
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degradation in the collagen-induced arthritis model of RA, and in the STR/ort mouse OA model; and (7) identify metalloproteases that act in articular cartilage breakdown during the progression of OA in humans. These studies will produce mechanistic and structural information about the interactions of TIMPs and metalloproteinases and new insights into therapeutic approaches for arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TISSUE DEGRADATION
SPECIFIC
CYSTEINE
PROTEASES
AND
ECM
Principal Investigator & Institution: Bromme, Dieter; Associate Professor; Human Genetics; Mount Sinai School of Medicine of Nyu of New York University New York, NY 10029 Timing: Fiscal Year 2001; Project Start 15-MAY-2000; Project End 30-APR-2005 Summary: The overall objective of the proposed research is to characterize the role of tissue specific cathepsins in extracellular matrix (ECM) protein degradation in cartilage. Previously, we and others identified cathepsins K and S as the predominant cysteine proteases in osteoclasts and macrophages, respectively, and characterized the extremely potent ECM- degrading activities of both cathepsins. We demonstrated that cathepsin K also is expressed in rheumatoid arthritis (RA) synovial fibroblasts and in mono- as well multi-nucleated cells of subchondral bone. Our working hypothesis is that cathepsins K and S are directly involved in cartilage degradation in arthritic joints. Therefore, in vitro and in vivo experiments will be undertaken to further characterize the biological functions of these cathepsins and to determine if these cathepsins cause excessive ECM degradation in tissue-degenerative pathologies such as RA. The expression of human cathepsins K and S will be localized in RA and non-RA joints and synovial fluid and correlated with the focal sites of cartilage erosion. Primary synovial fibroblast cultures from RA and non- RA specimens will be characterized with respect to the expression and secretion of both cathepsin activities. Substrate specificity studies will be undertaken with purified human cartilage proteins as well as with intact cartilage using recombinant cathepsins K and S. identified cleavage sites in ECM substrates will be used to produce specific neoepitope antibodies to identify cathepsin-released cleavage products in normal and diseased cartilage and synovial fluid. The extracellular processing of the cathepsin precursors will be assessed using known ECM-resident proteases. Furthermore, cooperative effects of cathepsin and MMP activities towards cartilage proteins will be determined. Ex-vivo cell models of cartilage erosion and antigen-induced arthritis mouse models using cathepsin K- deficient animals will be exploited to characterize the contribution of cathepsins K and S to the cartilage degeneration under non-inflammatory and inflammatory conditions. Altogether, these studies should determine the role of cathepsins K and S in ECM-protein degradation, and investigate novel strategies for the treatment of RA and other disorders with excessive ECM-degradation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF ARTHRITIS WITH INTERLEUKINS Principal Investigator & Institution: Lauermann, Vit; Rubicon Laboratory, Inc. 7904 Springway Rd Baltimore, MD 21204 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2004 Summary: (provided by applicant): The overall goal of this project is to develop a therapeutic method for targeted delivery of IL-4 to arthritic joints. Rheumatoid arthritis
128 Rheumatoid Arthritis
is an autoimmune disease characterized by progressive cartilage and bone erosion. Cytokines are important modulators of immune responses and IL-4 is an attractive cytokine for treating arthritis. Local administration of IL-4 has therapeutic effects in patients with moderate arthritis. However, the therapeutic efficacy of the cytokine is limited due to its toxicity. To improve the cytokine therapeutic effect, its concentration in a disease site has to be increased without causing undesirable side effects. The proposed method suppresses the biological activity of the administered cytokine until it reaches proximity of a target cell. The cytokine is then rendered active and concentrates in a disease site. The cytokine concentration in arthritic joints can reach levels that have desired therapeutic effects without systemic toxicity. This targeted delivery approach can be adapted for other cytokines and diseases and can be used as adjuvant to other treatments or stand alone. In Phase I we will develop the biological reagents and test them in vitro. We will use these reagents in Phase II in preclinical studies evaluating treatment of arthritis in animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF EARLY AGGRESSIVE RHEUMATOID ARTHRITIS TEAR Principal Investigator & Institution: Moreland, Larry W. Professor of Medicine and Associate Dean; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 26-SEP-2003 Summary: (provided by applicant): Combinations of biologic agents and traditional disease modifying antirheumatic drugs (DMARDs) are being increasingly used in early RA. The effectiveness and side effects of different regimens, however, are unlikely to be compared in clinical trials performed by pharmaceutical companies. The proposed multicenter trial, Treatment of Early Aggressive Rheumatoid Arthritis (TEAR), represents the first pre-planned 5-year trial of biologic/DMARD combinations in early RA. Thus, the TEAR trial might provide information of value to RA patients, rheurnatologists and the Food & Drug Administration. The proposed trial is a 3-arm study comparing 2 different combinations (anti-TNF plus methotrexate versus methotrexate plus hydroxychloroquine plus sulfasalazine) versus monotherapy (methotrexate) in patients with early RA who have an "aggressive" clinical phenotype defined by presence of erosions on hand or feet radiographs, or positive serum rheumatoid factor, plus active synovitis of multiple joints. A steering committee of clinical researchers involved with RA trials has been formed to design the TEAR trial. The clinical trials planning grant is needed for the following specific aims: (1) to conduct meetings and conference calls of steering committee to write the grant for funding of the TEAR trial; (2) to develop study materials including data collection instruments, design and preparation for the quality control procedures, informed consent prototype, manual of operations and procedures (MOPP); (3) to secure definite commitments for participation from pharmaceutical companies and clinical research sites; (4) to design appropriate pharmacogenetic studies that potentially would identify patients who have a significant positive clinical response in this trial; and (6) to perform preliminary analysis of existing data to refine the outcomes to be used in this clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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•
Project Title: TREATMENT MARINE/BOTANICAL OILS
OF
RHEUMATOID
ARTHRITIS-
Principal Investigator & Institution: Zurier, Robert B. Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The object of this proposal is to determine whether treatment of rheumatoid arthritis (RA) with a combination of fish oil and borage seed oil is superior to treatment with either oil alone. Fish oil is rich in the antiinflammatory n3 unsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and borage oil contains gammalinolenic acid (GLA), an n6 unsaturated fatty acid with antiinflammatory and immunomodulatory properties. Administration of borage oil and of fish oil both suppress the clinical manifestations of RA. Animal studies indicate that the mechanisms whereby fish oil suppresses inflammation are both similar to and different from the means by which GLA reduces inflammation and that the combination treatment is more effective than each treatment alone. This proposal is for a multi-center, two-year, phase 3, double-masked, placebo-controlled trial of 375 patients, which includes 4 treatment groups: 1) corn oil as a polyunsaturated fatty acid control; 2) fish oil; 3) borage oil; 4) fish oil plus borage oil. Radiographic analysis (Sharp Scores) of hands and feet will be done at baseline, 12, and 24 months. Biochemical and molecular mechanisms whereby the fatty acid treatments influence activation of monocytes (cytokine and oxygen radical generation), and T lymphocytes (proliferation, cytokine production, Th1/Th2 skewing, signaling events) will be investigated. Results of the cell activation (ex vivo) studies will be correlated with clinical outcomes. Results of these studies should raise awareness of the usefulness of naturally occurring oils in inflammatory diseases, lead to more rational use of fatty acids in treatment of inflammatory arthritis, and provide a greater understanding of the mechanisms of action of antiinflammatory fatty acids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TYPE V COLLAGENASE IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Pourmotabbed, Tayebeh; Molecular Sciences; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 01-FEB-1993; Project End 31-MAR-2003 Summary: The degradation of the extracellular matrix requires the coordinated action of enzymes which constitute a family of metalloproteinases. Nowhere is this degradative ability more apparent than in rheumatoid arthritis. In this disease, excessive production of metalloproteinases mediates the degradation of articular cartilage and subchondral bone, resulting in severe deformity. Type V collagenase/gelatinase B is a member of this multigene family of enzymes which exhibits high specificity for denatured collagen, degrades native types V and XI collagen which is a structural component of cartilage. The main objective of the proposed research is to understand the regulation of this enzyme and to define its precise role and significance in rheumatoid arthritis. Towards the achievement of this goal we propose to 1. Investigate the role of hemopexin-like carboxy terminal domain in Ca2+-dependent activation of gelatinase B. This will be done by generating a series of COOH-terminal (CTD) truncated mutant and assessing the effect of truncation on enzyme latency and conformation. The CTD "regulatory peptide" will be identified by generating a series of GST-CDT peptide and the effect of each peptide on activity of CTD-truncated enzymes will be examined, 2. Substantiate the hypothesis that a salt linkage present in gelatinase B catalytic domain is responsible for
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Ca2+-independent activity of the enzyme. The NH2- and COOH-terminal regions of catalytic domain will be cross linked and the effect of cross linking on the Ca2+dependent activity of the enzyme will be assessed, 3. Identify the TIMP-1 binding residues within the active site of gelatinase B by alanine-scanning site-directed mutagenesis, 4. Investigate the role of the fibronectin-like binding domain in substrate specificity of the enzyme by generating deletion mutants. Specific amino acid residues responsible for substrate specificity of the enzyme will be identified by alanine-scanning site directed mutagenesis and finally 5. Region(s) of gelatinase B responsible for proteinprotein and protein- matrix membrane interaction will be identified using truncated mutants generated above. These studies will further our understanding on the action of this enzyme and may lead to new therapeutic approaches which would focus on protection of articular tissues from degradation in rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UNIQUE SURFACE STRUCTURES ON SYNOVIAL CELLS Principal Investigator & Institution: Fox, David A. Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-MAR-2007 Summary: (provided by the applicant): In rheumatoid arthritis (RA) inflammation and ultimate destruction of articular structures are accompanied by extensive infiltration of synovium by T lymphocytes and macrophages, and hyperplasia of synovial fibroblasts (SF). The role of T lymphocytes remains controversial, with no conclusive proof for T cell directed autoimmunity as the cause of RA. We have taken several approaches to better understand pathways of T cell activation and of the role of T cells in RA, including generation of monoclonal antibodies to novel T cell surface antigens, and ligands of surface structures important for T cell activation, including ligands expressed on SF. In addition we have developed evidence that T cells, even resting T cells, can interact with SF in a bi-directional manner. Thus SF can function as potent accessory cells for T cell activation, while resting T cells can stimulate a proinflammatory pattern of gene expression in SF, even in the absence of stimuli that activate the T cell. We have termed this ability of unactivated T lymphocytes to stimulate the SF "effector function of resting T cells." We now propose that a significant component of the aggressive behavior of SF in RA arises from direct interactions between T cells and RA SF. We also hypothesize that the molecular basis for this unusual and pathogenic program of cell differentiation arises from a unique immunologic synapse formed between the T lymphocyte and the SF. The current proposal would further analyze the molecular interactions between T cells and SF and the functional consequences of these interactions, using both morphologic and immunologic approaches. A novel ligand of CD6 expressed by SF will be molecularly characterized and functionally studied. New antibodies will be generated to analyze the T cell/SF microarray analysis of SF gene expression, and quantitative interaction, directed at both known and novel cell surface molecules and at the secreted CD26-related cell interaction molecule attractin. Activation of SF will be studied using measurement of relevant RNA species and protein products, such as osteoclast differentiation factor, cytokines, and tissue destructive proteases. The proposed studies represent a fresh approach to understanding RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: USE OF FAS LIGAND TO SUPPRESS ARTHRITIS Principal Investigator & Institution: Bellgrau, Donald L. Professor and Program Leader; Globeimmune, Inc. 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-DEC-2001 Summary: Preliminary reports by several groups have demonstrated the potential for Fas ligand-based therapy to prevent transplant rejection, to treat autoimmune disease, to induce immunological tolerance and to treat cancer. The "Use of Fas Ligand to Suppress T-lymphocyte mediated Immune Responses" is protected by U.S. Patent No. 5,759,536, Donald Bellgrau and Richard C. Duke, Inventors. CERES Pharmaceuticals has licensed this Technology from the University of Colorado. The overall goal of this Phase I SBIR application is to develop and test in a well-established mouse model of arthritis, commercially-useful recombinant adenoviral gene therapy vectors encoding mutated versions of Fas ligand with enhanced therapeutic potential. These vectors and strategies for their production and application to treat human rheumatoid arthritis (U.S. Patents Pending) will be licensed to Pharmaceutical and/or Biotechnology companies for use in filing Investigational New Drug (IND) Applications with the FDA in anticipation of phase I clinical trails in humans. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VIRGINIA MASON/UCHSC AUTOIMMUNE PREVENTION CENTER Principal Investigator & Institution: Eisenbarth, George S. Executive Director; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The proposed Autoimmunity Prevention Center combines the efforts of investigators with faculty appointments at the University of Colorado Health Sciences Center (UCHSC), Denver Colorado and the Virginia Mason Center (University of Washington) in Seattle Washington. Affiliated institutions at the UCHSC include the Barbara Davis Center for Childhood Virginia Mason Center and the Barbara Davis Center/UCHSC have a long history of collaborative efforts and complementary expertise in the field of immunology of autoimmunity. In particular the laboratories of Brian Kotzin and reagents as part of the Immune Tolerance Network. T cell clones derived at the Barbara Davis Center are being utilized by Dr. Nepom to create tetramers to identify diabetogenic T cells. Drs. Eisenbarth and Greenbaum are co-investigators on an NIH study of diabetes protective HLA alleles. A joint clinical trial of mycophenolate mofetil and IL2 receptor antibodies for new onset diabetes is about to commence at the Virginia Mason Center and the Barbara Davis Center. We are committed to a collaborative effort between the two institutions, with Dr. Eisenbarth going on sabbatical to work in the laboratories of Kwok and Nepom for 6 months beginning in July of 2001. In addition, we welcome the opportunity to extend collaborative efforts to a prevention Center Network. Faculty for the Prevention Center have been recruited from the Departments of Immunology, Pediatrics, Medicine, and Preventive Medicine, Epidemiology, and the Human Medical Genetics Program. Within the Departments of Pediatrics and Medicine, subspecialties include endocrinology, rheumatology, clinical immunology, nephrology, pulmonary, and gastroenterology. There are unique resources for clinical investigation and strong basic science faculty and in many instances a track record for combining basic and clinical investigation. For the current proposal, the DAISY prospective study of children developing diabetes provides an
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essential resource and paradigm for the study of human autoimmunity in families and the general population and we are looking forward to joint studies of celiac disease, rheumatoid arthritis, polychondritis, and type 1 diabetes. Three Projects are proposed. Project 1 Quantitate and Characterize T cells of Type 1 diabetes; Project 2 Initiate studies of rheumatoid arthritis modeled on studies such as DAISY; Project 3 Analyze the development of celiac disease autoimmunity of infants followed from birth. Two Pilot studies are also proposed, one evaluating polychondritis and the other evaluating in basic animal models the importance of specific signaling pathways (CD32 and phosphatidylserine receptor) to maintenance of tolerance and development of autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: WHY IS CARDIAC RISK INCREASED IN RHEUMATIOD ARTHRITIS Principal Investigator & Institution: Solomon, Daniel H.; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): While rheumatoid arthritis is primarily considered a condition affecting the joints and impairing function, past data suggest that cardiac disease represents the number one cause of mortality in rheumatoid arthritis. However, the adjusted rates of cardiovascular death and myocardial infarction in rheumatoid arthritis are poorly characterized. Additionally, whether the increased cardiovascular risk is because of the medications used for rheumatoid arthritis or the underlying disease severity is unknown. The proposed research has two major aims: 1) to quantify the rates of cardiovascular death and myocardial infarction in patients with rheumatoid arthritis after controlling for known cardiovascular risk factors and 2) to determine the contribution of rheumatoid arthritis medication exposure and disease severity to cardiovascular disease rates. Prior work on this issue has largely been conducted in referral populations and attempts to control for known cardiovascular risk factors have been poor. We propose to study this issue in a large Medicare/Medicaid database that we have extensive experience working with. This database contains information on over 2 million patients followed for 10 years and includes diagnoses and procedures for all physician and inpatient visits. As well, prescription data from a large pharmacy benefits program has been integrated into this database allowing for a complete characterization of an individual patients medication exposure. While any one diagnosis of rheumatoid arthritis may not be accurate in such a database, the project entails a validation substudy to develop an algorithm for selecting patients with a high probability of having rheumatoid arthritis. The proposed project will be an important advance in this area because of the large number of patients with rheumatoid arthritis to be included (over 5,000), the community-based nature of their care, the ability to control for known cardiovascular risk factors, the extensive medication information allowing for us to explore key hypotheses regarding corticosteroid exposure, and the attempt to simultaneously control for disease severity Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WORK DISABILITY-- PERSONS WITH RHEUMATOID ARTHRITIS Principal Investigator & Institution: Allaire, Saralynn; Boston University Medical Campus 715 Albany St, 560 Boston, MA 02118 Timing: Fiscal Year 2001; Project Start 24-SEP-2001; Project End 31-AUG-2006
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Summary: Work disability is a major burden of rheumatoid arthritis (RA). The most cited study of RA work disability was conducted 15 years ago. Since then, remarkable changes in the macro-economy, in the nature of work, in governmental income support programs, and in the treatment of the disease have occurred. As these are likely to have affected RA work disability, new and more sensitive data are clearly needed. The study's primary aim is to assess work disability among employed persons with RA using a prospective study design. The secondary aims are to assess RA work disability in two increasingly important subgroups, retirement aged persons and minorities, and to assess current risk factors for RA work disability. Risk factors of particular interest are work characteristics that reflect the changing nature of work and consistent use of disease modifying anti-rheumatic drugs. We will study two measures of work disability, work cessation and limitation in ability to work. Subjects will be drawn from patients with RA participating in the National Data Bank for Rheumatic Diseases, a large, national cohort of arthritis patients. 4615 employed subjects with RA aged 18 through 67 will form the full sample; subsets of subjects will be used for some specific aims. Additional patients will be recruited into the NDB cohort to ensure that newly diagnosed patients are included. Subjects will be assessed at the beginning of the project and yearly thereafter for three years for both work disability and factors affecting it. Work cessation is any work stoppage age 65. Limitation in ability to work will be measured using the Work Limitations Questionnaire (WLQ). Incidence of work cessation will be estimated using the Kaplan-Meier method. Trends over time in the WLQ will be examined using random effects regression models. The same methods will be used to examine work disability among retirement-aged subjects. ANCOVA and Cox regression will be used to examine differences in work disability between minorities and Whites. Cox regression, mixed-effects and 1ogistic regression analyses will assess the strength of risk factors. Because of large sample sizes, power estimates indicate results can be determined with fine precision. The information gained will be used for resource allocation, for determining which groups of persons with RA have special needs, and for designing targeted interventions to help persons with RA maintain employment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: WRITTEN EMOTIONAL EXPRESSION ABOUT TRAUMAS Principal Investigator & Institution: Smyth, Joshua M. Assistant Professor; Psychology; Syracuse University Syracuse, NY 13210 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2005 Summary: (investigator's abstract): The overall aim of this application is to extend work on a new psychological phenomenon that may have direct clinical relevance for a variety of somatic diseases. The basic finding of interest relates to observed relationships between a brief writing task that creates emotional expression about past traumas, and salutary effects on some affective, psychophysiological, physiological, and symptom outcome measures. Participants examined in the majority of previous studies were typically healthy. In one previous study, however, the writing task produced reductions in symptoms in patients with asthma or rheumatoid arthritis. The proposed experiment attempts to extend such work as such a demonstration could suggest that treatment procedures based on the writing task be developed and employed in these and other medical conditions. A shift in affect, and presumably cognitive processes as well, apparently occurs in the interval between the written emotional expression and subsequent assessments. Current theorizing about this observation focuses on the idea that the cognitive representation of traumatic memories is altered in this period, resulting in reductions in negative affect and physiological arousal although there is no
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documentation of any such process. The primary goals of the study are to (1) determine the effect of written emotional expression on subsequent symptomatology, mood, and disease status in patients with asthma or rheumatoid arthritis, and (2) establish what psychological and/or social pathway(s) the manipulation may be operating through. Patients with asthma or rheumatoid arthritis will be assigned randomly to either experimental (writing about the most traumatic or stressful event they remember) or control condition (writing about neutral topics). Affect, cognition, social contacts, and symptoms will be assessed several times a day using palm top computers for one week prior to and two weeks following the manipulation. Disease status will be measured every six months for a period of two years, and quality of life measures will also be taken. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “rheumatoid arthritis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for rheumatoid arthritis in the PubMed Central database: •
"Rheumatoid Arthritis": A balanced overview of current research. by Huizinga TW. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128902
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A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273]. by Collantes E, Curtis SP, Lee KW, Casas N, McCarthy T, Melian A, Zhao PL, Rodgers DB, McCormick CL, Lee M, Lines CR, Gertz BJ. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115849
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A new model for rheumatoid arthritis? by McDevitt H. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129990
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A novel mechanism for the regulation of IFN-[gamma] inducible protein-10 expression in rheumatoid arthritis. by Hanaoka R, Kasama T, Muramatsu M, Yajima N, Shiozawa F, Miwa Y, Negishi M, Ide H, Miyaoka H, Uchida H, Adachi M. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165028
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A revival of the B cell paradigm for rheumatoid arthritis pathogenesis? by Benoist C, Mathis D. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129991
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Activation of synovial fibroblasts in rheumatoid arthritis: lack of expression of the tumour suppressor PTEN at sites of invasive growth and destruction. by Pap T, Franz JK, Hummel KM, Jeisy E, Gay R, Gay S. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17804
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Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue. by O'Hara R, Murphy EP, Whitehead AS, FitzGerald O, Bresnihan B. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17807
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Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. by Hagfors L, Leanderson P, Skoldstam L, Andersson J, Johansson G. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194256
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Association of MHC and rheumatoid arthritis: Association of RA with HLA-DR4 - the role of repertoire selection. by Roudier J. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130006
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Association of MHC and rheumatoid arthritis: HLA-DR4 and rheumatoid arthritis studies in mice and men. by Fugger L, Svejgaard A. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130004
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Association of MHC and rheumatoid arthritis: Regulatory role of HLA class II molecules in animal models of RA - studies on transgenic/knockout mice. by Taneja V, David CS. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130003
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Association of MHC and rheumatoid arthritis: Why is rheumatoid arthritis associated with the MHC genetic region? An introduction. by Holmdahl R. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130002
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Association of MHC and rheumatoid arthritis:HLA polymorphisms in phenotypic variants of rheumatoid arthritis. by Weyand CM, Goronzy JJ. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130005
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B cells in rheumatoid arthritis. by Kim HJ, Berek C. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129995
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B lymphocytopenia in rheumatoid arthritis is associated with the DRB1 shared epitope and increased acute phase response. by Wagner U, Kaltenhauser S, Pierer M, Wilke B, Arnold S, Hantzschel H. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125293
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Bone loss: Quantitative imaging techniques for assessing bone mass in rheumatoid arthritis. by Njeh CF, Genant HK. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128873
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Cardiovascular risk in rheumatoid arthritis versus osteoarthritis: acute phase response related decreased insulin sensitivity and high-density lipoprotein cholesterol as well as clustering of metabolic syndrome features in rheumatoid arthritis. by Dessein PH, Stanwix AE, Joffe BI. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125299
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Cell-cell interactions in synovitis: Antigen presenting cells and T cell interaction in rheumatoid arthritis. by Aarvak T, Natvig JB. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128879
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Cell-cell interactions in synovitis: Interactions between T cells and B cells in rheumatoid arthritis. by Weyand CM, Goronzy JJ, Takemura S, Kurtin PJ. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128875
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Citrullination: a small change for a protein with great consequences for rheumatoid arthritis. by van Venrooij WJ, Pruijn GJ. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130012
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Clonal expansion is a characteristic feature of the B-cell repertoire of patients with rheumatoid arthritis. by Itoh K, Patki V, Furie RA, Chartash EK, Jain RI, Lane L, Asnis SE, Chiorazzi N. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17803
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Cloning and expression of a novel human antibody --antigen pair associated with Felty's syndrome. by Ditzel HJ, Masaki Y, Nielsen H, Farnaes L, Burton DR. 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16851
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Correlation of the score for subjective pain with physical disability, clinical and radiographic scores in recent onset rheumatoid arthritis. by Sarzi-Puttini P, Fiorini T, Panni B, Turiel M, Cazzola M, Atzeni F. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117789
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Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. by Dong H, Strome SE, Matteson EL, Moder KG, Flies DB, Zhu G, Tamura H, Driscoll CL, Chen L. 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151851
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Cross-Reactivity between the Rheumatoid Arthritis-Associated Motif EQKRAA and Structurally Related Sequences Found in Proteus mirabilis. by Tiwana H, Wilson C, Alvarez A, Abuknesha R, Bansal S, Ebringer A. 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96580
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Cytokine mRNA and protein expression in primary-culture and repeated-passage synovial fibroblasts from patients with rheumatoid arthritis. by Hirth A, Skapenko A, Kinne RW, Emmrich F, Schulze-Koops H, Sack U. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=83845
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Cytokine, activation marker, and chemokine receptor expression by individual CD4+ memory T cells in rheumatoid arthritis synovium. by Nanki T, E Lipsky P. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17818
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Cytokine-stimulated T cells induce macrophage IL-10 production dependent on phosphatidylinositol 3-kinase and p70S6K: implications for rheumatoid arthritis. by Foey A, Green P, Foxwell B, Feldmann M, Brennan F. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64854
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Decreased effector memory CD45RA+ CD62L- CD8+ T cells and increased central memory CD45RA- CD62L+ CD8+ T cells in peripheral blood of rheumatoid arthritis patients. by Maldonado A, Mueller YM, Thomas P, Bojczuk P, O'Connors C, Katsikis PD. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165030
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Detection of Mycobacterium tuberculosis Group Organisms in Human and Mouse Joint Tissue by Reverse Transcriptase PCR: Prevalence in Diseased Synovial Tissue Suggests Lack of Specific Association with Rheumatoid Arthritis. by Kempsell KE, Cox CJ, McColm AA, Bagshaw JA, Reece R, Veale DJ, Emery P, Isaacs JD, Gaston JS, Crowe JS. 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98089
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Differentiation of B Cells in the Nonlymphoid Tissue of the Synovial Membrane of Patients with Rheumatoid Arthritis. by Schroder AE, Greiner A, Seyfert C, Berek C. 1996 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40210
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Differentiation of naive CD4+ T cells towards T helper 2 cells is not impaired in rheumatoid arthritis patients. by van Roon JA, Glaudemans CA, Bijlsma JW, Lafeber FP. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193727
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Disease activity and risk of lymphoma in patients with rheumatoid arthritis: nested case-control study. by Baecklund E, Ekbom A, Sparen P, Feltelius N, Klareskog L. 1998 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28610
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Dominant T-Cell-Receptor [beta] Chain Variable Region V[beta]14+ Clones in Juvenile Rheumatoid Arthritis. by Grom AA, Thompson SD, Luyrink L, Passo M, Choi E, Glass DN. 1993 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47930
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Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. by Deeks JJ, Smith LA, Bradley MD. 2002 Sep 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126301
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Efficient adenoviral infection with I[kappa]B[alpha] reveals that macrophage tumor necrosis factor [alpha] production in rheumatoid arthritis is NF-[kappa]B dependent. by Foxwell B, Browne K, Bondeson J, Clarke C, de Martin R, Brennan F, Feldmann M. 1998 Jul 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20955
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Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. by Yamamoto N, Sakai F, Kon S, Morimoto J, Kimura C, Yamazaki H, Okazaki I, Seki N, Fujii T, Uede T. 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164290
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Expression and function of wingless and frizzled homologs in rheumatoid arthritis. by Sen M, Lauterbach K, El-Gabalawy H, Firestein GS, Corr M, Carson DA. 2000 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16008
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Extracellular mitochondrial DNA and oxidatively damaged DNA in synovial fluid of patients with rheumatoid arthritis. by Hajizadeh S, DeGroot J, TeKoppele JM, Tarkowski A, Collins LV. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193725
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Fibroblast biology: Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis. by Pap T, Muller-Ladner U, Gay RE, Gay S. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130137
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Fibroblast biology: Synovial fibroblasts in rheumatoid arthritis - leading role or chorus line? by Kontoyiannis D, Kollias G. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130133
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Gene expression induced by interleukin-17 in fibroblast-like synoviocytes of patients with rheumatoid arthritis: upregulation of hyaluronan-binding protein TSG-6. by Kehlen A, Pachnio A, Thiele K, Langner J. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165059
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Gene therapy in rheumatoid arthritis: how to target joint destruction? by Pap T, Muller-Ladner U, Gay R, Gay S. 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128862
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Genetic epidemiology: Approaches to the genetic analysis of rheumatoid arthritis. by John S, Worthington J. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128899
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Genetics of rheumatoid arthritis: confronting complexity. by Gregersen PK. 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128868
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High CXCR3 expression in synovial mast cells associated with CXCL9 and CXCL10 expression in inflammatory synovial tissues of patients with rheumatoid arthritis. by Ruschpler P, Lorenz P, Eichler W, Koczan D, Hanel C, Scholz R, Melzer C, Thiesen HJ, Stiehl P. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193722
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Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1. by d'Elia HF, Mattsson LA, Ohlsson C, Nordborg E, Carlsten H. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165058
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Human parvovirus B19 as a causative agent for rheumatoid arthritis. by Takahashi Y, Murai C, Shibata S, Munakata Y, Ishii T, Ishii K, Saitoh T, Sawai T, Sugamura K, Sasaki T. 1998 Jul 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20958
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IFN-[gamma] production in response to in vitro stimulation with collagen type II in rheumatoid arthritis is associated with HLA-DRB1*0401 and HLA-DQ8. by Berg L, Ronnelid J, Sanjeevi CB, Lampa J, Klareskog L. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17806
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IgVH genes from different anatomical regions, with different histopathological patterns, of a rheumatoid arthritis patient suggest cyclic re-entry of mature synovial B-cells in the hypermutation process. by Souto-Carneiro MM, Krenn V, Hermann R, Konig A, Muller-Hermelink HK. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17813
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IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. by Chabaud M, Lubberts E, Joosten L, van den Berg W, Miossec P. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30709
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Immune Response of HLA-DQ8 Transgenic Mice to Peptides from the Third Hypervariable Region of HLA-DRB1 Correlates with Predisposition to Rheumatoid Arthritis. by Zanelli E, Krco CJ, Baisch JM, Cheng S, David CS. 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39864
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Insights into rheumatoid arthritis derived from the Sa immune system. by Menard HA, Lapointe E, Rochdi MD, Zhou ZJ. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128869
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Internet hand x-rays: A comparison of joint space narrowing and erosion scores (Sharp/Genant) of plain versus digitized x-rays in rheumatoid arthritis patients. by Arbillaga HO, Montgomery GP, Cabarrus LP, Watson MM, Martin L, Edworthy SM. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113251
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Is day care equivalent to inpatient care for active rheumatoid arthritis? Randomised controlled clinical and economic evaluation. by Lambert CM, Hurst NP, Forbes JF, Lochhead A, Macleod M, Nuki G. 1998 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28498
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Is it Crohn's disease? A severe systemic granulomatous reaction to sulfasalazine in patient with rheumatoid arthritis. by Quallich LG, Greenson J, Haftel HM, Fontana RJ. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56591
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Isolation and characterization of rheumatoid arthritis synovial fibroblasts from primary culture --- primary culture cells markedly differ from fourth-passage cells. by Zimmermann T, Kunisch E, Pfeiffer R, Hirth A, Stahl HD, Sack U, Laube A, Liesaus E, Roth A, Palombo-Kinne E, Emmrich F, Kinne RW. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17827
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Limited T-Cell Receptor [beta]-Chain Heterogeneity Among Interleukin 2 ReceptorPositive Synovial T Cells Suggests a Role for Superantigen in Rheumatoid Arthritis. by Howell MD, Diveley JP, Lundeen KA, Esty A, Winters ST, Carlo DJ, Brostoff SW. 1991 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53044
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Macrophages in rheumatoid arthritis. by Kinne RW, Brauer R, Stuhlmuller B, PalomboKinne E, Burmester GR. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130001
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Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. by Gotzsche PC, Johansen HK. 1998 Mar 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28482
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Model studies directed toward the application of boron neutron capture therapy to rheumatoid arthritis: Boron delivery by liposomes in rat collagen-induced arthritis. by Watson-Clark RA, Banquerigo ML, Shelly K, Hawthorne MF, Brahn E. 1998 Mar 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19402
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Molecular profile of synovial fibroblasts in rheumatoid arthritis depends on the stage of proliferation. by Masuda K, Masuda R, Neidhart M, Simmen BR, Michel BA, MullerLadner U, Gay RE, Gay S. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125298
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Mosaic chromosomal aberrations in synovial fibroblasts of patients with rheumatoid arthritis, osteoarthritis, and other inflammatory joint diseases. by Kinne RW, Liehr T, Beensen V, Kunisch E, Zimmermann T, Holland H, Pfeiffer R, Stahl HD, Lungershausen W, Hein G, Roth A, Emmrich F, Claussen U, Froster UG. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64845
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New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study. by Cornelis F, Faure S, Martinez M, Prud'homme JF, Fritz P, Dib C, Alves H, Barrera P, de Vries N, Balsa A, Pascual-Salcedo D, Maenaut K, Westhovens R, Migliorini P, Tran TH, Delaye A, Prince N, Lefevre C, Thomas G, Poirier M, Soubigou S, Alibert O, Lasbleiz S, Fouix S, Bouchier C, Liote F, Loste MN, Lepage V, Charron D, Gyapay G, Lopes-Vaz A, Kuntz D, Bardin T, Weissenbach J. 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27966
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NF-kappaB in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. by Makarov SS. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128895
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p53 in rheumatoid arthritis: friend or foe? by Muller-Ladner U, Nishioka K. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129999
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Perforin and Granzyme A Expression Identifying Cytolytic Lymphocytes in Rheumatoid Arthritis. by Griffiths GM, Alpert S, Lambert E, McGuire J, Weissman IL. 1992 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48276
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Perinatal characteristics and risk of rheumatoid arthritis. by Jacobsson LT, Jacobsson ME, Askling J, Knowler WC. 2003 May 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155691
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Perturbation of the T cell repertoire in rheumatoid arthritis. by Wagner UG, Koetz K, Weyand CM, Goronzy JJ. 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24393
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Predominant selection of T cells specific for the glycosylated collagen type II epitope (263 --270) in humanized transgenic mice and in rheumatoid arthritis. by Backlund J, Carlsen S, Hoger T, Holm B, Fugger L, Kihlberg J, Burkhardt H, Holmdahl R. 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126607
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Regional analysis of p53 mutations in rheumatoid arthritis synovium. by Yamanishi Y, Boyle DL, Rosengren S, Green DR, Zvaifler NJ, Firestein GS. 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126618
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Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of Danish nationwide twin population. by Svendsen AJ, Holm NV, Kyvik K, Petersen PH, Junker P. 2002 Feb 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65056
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Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis. by Moreland L, Gugliotti R, King K, Chase W, Weisman M, Greco T, Fife R, Korn J, Simms R, Tesser J, Hillson J, Caldwell J, Schnitzer T, Lyons D, Schwertschlag U. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34114
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Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. by Goldbach-Mansky R, Lee J, McCoy A, Hoxworth J, Yarboro C, Smolen JS, Steiner G, Rosen A, Zhang C, Menard HA, Zhou ZJ, Palosuo T, Van Venrooij WJ, Wilder RL, Klippel JH, Schumacher HR Jr, EI-Gabalawy HS. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17811
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Rheumatoid arthritis viewed using a headache paradigm. by Holmdahl R. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129997
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Rheumatoid arthritis, gold therapy, contact allergy and blood cytokines. by Svensson A, Moller H, Bjorkner B, Bruze M, Leden I, Theander J, Ohlsson K, Linder C. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65540
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Serum cartilage oligomeric matrix protein (COMP) decreases in rheumatoid arthritis patients treated with infliximab or etanercept. by Crnkic M, Mansson B, Larsson L, Geborek P, Heinegard D, Saxne T. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165057
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Smoking --gender interaction and risk for rheumatoid arthritis. by Krishnan E, Sokka T, Hannonen P. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165046
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Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. by Firestein GS, Echeverri F, Yeo M, Zvaifler NJ, Green DR. 1997 Sep 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23522
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Structural Requirements for Recognition of the HLA-Dw14 Class II Epitope: A Key HLA Determinant Associated with Rheumatoid Arthritis. by Hiraiwa A, Yamanaka K, Kwok WW, Mickelson EM, Masewicz S, Hansen JA, Radka SF, Nepom GT. 1990 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54890
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Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8. by Hayashida K, Nanki T, Girschick H, Yavuz S, Ochi T, Lipsky PE. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17828
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T cell homeostasis in patients with rheumatoid arthritis. by Koetz K, Bryl E, Spickschen K, O'Fallon WM, Goronzy JJ, Weyand CM. 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16846
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The expansion of CD4+CD28- T cells in patients with rheumatoid arthritis. by Pawlik A, Ostanek L, Brzosko I, Brzosko M, Masiuk M, Machalinski B, Gawronska-Szklarz B. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165060
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The genetics of rheumatoid arthritis and the need for animal models to find and understand the underlying genes. by Jirholt J, Lindqvist AK, Holmdahl R. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128884
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The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis. by McCoy JM, Wicks JR, Audoly LP. 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151107
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The T-Cell-Receptor Repertoire in the Synovial Fluid of a Patient with Rheumatoid Arthritis is Polyclonal. by Uematsu Y, Wege H, Straus A, Ott M, Bannwarth W, Lanchbury J, Panayi G, Steinmetz M. 1991 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52543
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The yin and yang of rheumatoid arthritis. by Birmingham K. 2003 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=213499
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Upregulated hypoxia inducible factor-1[alpha] and -2[alpha] pathway in rheumatoid arthritis and osteoarthritis. by Giatromanolaki A, Sivridis E, Maltezos E, Athanassou N, Papazoglou D, Gatter KC, Harris AL, Koukourakis MI. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165055
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Urinary Excretion of Thiol Compounds in Patients with Rheumatoid Arthritis. by Rojkovich B, Nagy E, Prohle T, Poor G, Gergely P. 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95754
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Use of soluble peptide --DR4 tetramers to detect synovial T cells specific for cartilage antigens in patients with rheumatoid arthritis. by Kotzin BL, Falta MT, Crawford F, Rosloniec EF, Bill J, Marrack P, Kappler J. 2000 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26656
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Use of Two-Dimensional Gel Electrophoresis To Measure Changes in Synovial Fluid Proteins from Patients with Rheumatoid Arthritis Treated with Antibody to CD4. by Smith MA, Bains SK, Betts JC, Choy EH, Zanders ED. 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96017
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VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients. by Takeuchi E, Tanaka T, Umemoto E, Tomita T, Shi K, Takahi K, Suzuki R, Ochi T, Miyasaka M. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153839
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with rheumatoid arthritis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “rheumatoid arthritis” (or synonyms) into the search box, and click “Go.” The following is the type of 6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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output you can expect from PubMed for rheumatoid arthritis (hyperlinks lead to article summaries): •
A biologically important single nucleotide polymorphism within the toll-like receptor-4 gene is not associated with rheumatoid arthritis. Author(s): Kilding R, Akil M, Till S, Amos R, Winfield J, Iles MM, Wilson AG. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 340-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846053&dopt=Abstract
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A case of multiple sclerosis associated with rheumatoid arthritis and positive anticardiolipin antibodies. Author(s): Mpofu S, Moots RJ. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 376. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634248&dopt=Abstract
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A case of orbital myositis associated with rheumatoid arthritis. Author(s): Fadini GP. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 383; Author Reply 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634254&dopt=Abstract
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A comparison of self-reports of distress and affective disorder diagnoses in rheumatoid arthritis: a receiver operator characteristic analysis. Author(s): McQuillan J, Fifield J, Sheehan TJ, Reisine S, Tennen H, Hesselbrock V, Rothfield N. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 368-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794793&dopt=Abstract
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A comparison of ultrasonography and magnetic resonance imaging in the evaluation of temporomandibular joint involvement in rheumatoid arthritis and psoriatic arthritis. Author(s): Melchiorre D, Calderazzi A, Maddali Bongi S, Cristofani R, Bazzichi L, Eligi C, Maresca M, Ciompi M. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 673-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709544&dopt=Abstract
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A longitudinal study of rheumatoid arthritis in South Africans. Author(s): Tikly M, Zannettou N, Hopley M. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2003 February 5; 5(1): 2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827063&dopt=Abstract
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A poly(ADP-ribose) polymerase haplotype spanning the promoter region confers susceptibility to rheumatoid arthritis. Author(s): Pascual M, Lopez-Nevot MA, Caliz R, Ferrer MA, Balsa A, Pascual-Salcedo D, Martin J. Source: Arthritis and Rheumatism. 2003 March; 48(3): 638-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632415&dopt=Abstract
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A prospective study of sicca symptoms in patients with rheumatoid arthritis. Author(s): Brun JG, Madland TM, Jonsson R. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687509&dopt=Abstract
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A question of transformation: the synovial fibroblast in rheumatoid arthritis. Author(s): Davis LS. Source: American Journal of Pathology. 2003 May; 162(5): 1399-402. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707022&dopt=Abstract
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A rationale for the use of summary measurements for the assessment of the effects of rheumatoid arthritis therapies. Author(s): Schiff M. Source: Clinical Therapeutics. 2003 March; 25(3): 993-1001. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852713&dopt=Abstract
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A simplified disease activity index for rheumatoid arthritis for use in clinical practice. Author(s): Smolen JS, Breedveld FC, Schiff MH, Kalden JR, Emery P, Eberl G, van Riel PL, Tugwell P. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 244-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595618&dopt=Abstract
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A single infusion of infliximab increases the serum endostatin level in patients with rheumatoid arthritis. Author(s): Kucharz EJ, Gozdzik J, Kopec M, Kotulska A, Lewicki M, Pieczyrak R, Widuchowska M, Zakliczynska H, Szarzynska-Ruda M, Zycinska-Debska E. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 273-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747296&dopt=Abstract
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Abandoned therapies and unpublished trials in rheumatoid arthritis. Author(s): Keystone EC. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 253-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707578&dopt=Abstract
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Aberrant activation of B cells in patients with rheumatoid arthritis. Author(s): Lindenau S, Scholze S, Odendahl M, Dorner T, Radbruch A, Burmester GR, Berek C. Source: Annals of the New York Academy of Sciences. 2003 April; 987: 246-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727646&dopt=Abstract
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Abnormal vitamin B(6) status is associated with severity of symptoms in patients with rheumatoid arthritis. Author(s): Chiang EP, Bagley PJ, Selhub J, Nadeau M, Roubenoff R. Source: The American Journal of Medicine. 2003 March; 114(4): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681455&dopt=Abstract
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Acetabular revision with impacted morselized cancellous bone graft and a cemented cup in patients with rheumatoid arthritis: three to fourteen-year follow-up. Author(s): Schreurs BW, Thien TM, de Waal Malefijt MC, Buma P, Veth RP, Slooff TJ. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 April; 85-A(4): 647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672840&dopt=Abstract
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Activin A induces cell proliferation of fibroblast-like synoviocytes in rheumatoid arthritis. Author(s): Ota F, Maeshima A, Yamashita S, Ikeuchi H, Kaneko Y, Kuroiwa T, Hiromura K, Ueki K, Kojima I, Nojima Y. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2442-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130463&dopt=Abstract
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Acute, non-obstructive, sterile cholecystitis associated with etanercept and infliximab for the treatment of juvenile polyarticular rheumatoid arthritis. Author(s): Foeldvari I, Kruger E, Schneider T. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 908-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922972&dopt=Abstract
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Add-on or step-up trials for new drug development in rheumatoid arthritis: a new standard? Author(s): Boers M. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1481-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794813&dopt=Abstract
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Addressing the safety of anakinra in patients with rheumatoid arthritis. Author(s): Fleischmann RM. Source: Rheumatology (Oxford, England). 2003 May; 42 Suppl 2: Ii29-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817093&dopt=Abstract
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Age at menarche in juvenile rheumatoid arthritis. Author(s): Rusconi R, Corona F, Grassi A, Carnelli V. Source: J Pediatr Endocrinol Metab. 2003 March; 16 Suppl 2: 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729405&dopt=Abstract
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Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. Author(s): Wunder A, Muller-Ladner U, Stelzer EH, Funk J, Neumann E, Stehle G, Pap T, Sinn H, Gay S, Fiehn C. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 May 1; 170(9): 4793-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707361&dopt=Abstract
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All-cause mortality and vascular events among patients with rheumatoid arthritis, osteoarthritis, or no arthritis in the UK General Practice Research Database. Author(s): Watson DJ, Rhodes T, Guess HA. Source: The Journal of Rheumatology. 2003 June; 30(6): 1196-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784389&dopt=Abstract
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Allele and antigen-specific treatment of rheumatoid arthritis: a double blind, placebo controlled phase 1 trial. Author(s): Kavanaugh A, Genovese M, Baughman J, Kivitz A, Bulpitt K, Olsen N, Weisman M, Matteson E, Furst D, van Vollenhoven R, Anderson J, Cohen S, Wei N, Meijerink J, Jacobs C, Mocci S. Source: The Journal of Rheumatology. 2003 March; 30(3): 449-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610799&dopt=Abstract
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Aminotransferase levels during treatment of rheumatoid arthritis with leflunomide in clinical practice. Author(s): Hoi A, Littlejohn GO. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 379. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634251&dopt=Abstract
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An exceptional radiographic presentation of bilateral insufficiency fractures of the proximal tibia in a patient with rheumatoid arthritis. Author(s): Vanhoof J, Landewe S, Vandevenne J, Geusens P. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594125&dopt=Abstract
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An index of the three core data set patient questionnaire measures distinguishes efficacy of active treatment from that of placebo as effectively as the American College of Rheumatology 20% response criteria (ACR20) or the Disease Activity Score (DAS) in a rheumatoid arthritis clinical trial. Author(s): Pincus T, Strand V, Koch G, Amara I, Crawford B, Wolfe F, Cohen S, Felson D. Source: Arthritis and Rheumatism. 2003 March; 48(3): 625-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632413&dopt=Abstract
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An open label study to establish dosing recommendations for nabumetone in juvenile rheumatoid arthritis. Author(s): Goodman S, Howard P, Haig A, Flavin S, Macdonald B. Source: The Journal of Rheumatology. 2003 April; 30(4): 829-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672207&dopt=Abstract
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Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebocontrolled trial. Author(s): Fleischmann RM, Schechtman J, Bennett R, Handel ML, Burmester GR, Tesser J, Modafferi D, Poulakos J, Sun G. Source: Arthritis and Rheumatism. 2003 April; 48(4): 927-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687534&dopt=Abstract
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Anakinra: the first interleukin-1 inhibitor in the treatment of rheumatoid arthritis. Author(s): Kary S, Burmester GR. Source: Int J Clin Pract. 2003 April; 57(3): 231-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723729&dopt=Abstract
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Analysis of the cell infiltrate and expression of proinflammatory cytokines and matrix metalloproteinases in arthroscopic synovial biopsies: comparison with synovial samples from patients with end stage, destructive rheumatoid arthritis. Author(s): Smeets TJ, Barg EC, Kraan MC, Smith MD, Breedveld FC, Tak PP. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 635-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810425&dopt=Abstract
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Anterior tibial compartment syndrome due to the pyomyositis in a patient with rheumatoid arthritis. A case report. Author(s): Aynaci O, Onder C, Kalaycioglu A. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2003 February; 70(1): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639625&dopt=Abstract
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Antibody-mediated stripping of CD4 from lymphocyte cell surface in patients with rheumatoid arthritis. Author(s): Hepburn TW, Totoritis MC, Davis CB. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 54-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509613&dopt=Abstract
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Anticitrullinated protein/peptide antibody and its role in the diagnosis and prognosis of early rheumatoid arthritis. Author(s): van Venrooij WJ, Hazes JM, Visser H. Source: The Netherlands Journal of Medicine. 2002 November; 60(10): 383-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607587&dopt=Abstract
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Anti-cyclic citrullinated peptide antibodies in advanced rheumatoid arthritis. Author(s): Pinheiro GC, Scheinberg MA, Aparecida da Silva M, Maciel S. Source: Annals of Internal Medicine. 2003 August 5; 139(3): 234-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899598&dopt=Abstract
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Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Author(s): Bas S, Genevay S, Meyer O, Gabay C. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 677-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709545&dopt=Abstract
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Anti-cyclic citrullinated peptide antibody in early rheumatoid arthritis: comment on the editorial by Scott. Author(s): van Venrooij WJ, van de Putte LB, van den Hoogen FH. Source: Arthritis and Rheumatism. 2003 March; 48(3): 857; Author Reply 857-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632446&dopt=Abstract
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Anti-cytokines and cytokines in the treatment of rheumatoid arthritis. Author(s): Taylor PC. Source: Current Pharmaceutical Design. 2003; 9(14): 1095-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769749&dopt=Abstract
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Anti-glomerular basement membrane antibody-associated renal failure in a patient with leflunomide-treated rheumatoid arthritis. Author(s): Bruyn GA, Veenstra RP, Halma C, Grond J. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1164-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687568&dopt=Abstract
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Anti-inflammatory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritis. Author(s): Cutolo M, Sulli A, Ghiorzo P, Pizzorni C, Craviotto C, Villaggio B. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634225&dopt=Abstract
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Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis. Author(s): Nakahara H, Song J, Sugimoto M, Hagihara K, Kishimoto T, Yoshizaki K, Nishimoto N. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1521-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794819&dopt=Abstract
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Antinuclear antibodies following infliximab treatment in patients with rheumatoid arthritis or spondylarthropathy. Author(s): De Rycke L, Kruithof E, Van Damme N, Hoffman IE, Van den Bossche N, Van den Bosch F, Veys EM, De Keyser F. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1015-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687543&dopt=Abstract
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Apoptosis in rheumatoid arthritis. Author(s): Baier A, Meineckel I, Gay S, Pap T. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 274-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707581&dopt=Abstract
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Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. Author(s): Uchida T, Fukawa A, Uchida M, Fujita K, Saito K. Source: Journal of Proteome Research. 2002 November-December; 1(6): 495-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645617&dopt=Abstract
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Applying low disease activity criteria using the DAS28 to assess stability in patients with rheumatoid arthritis. Author(s): Vrijhoef HJ, Diederiks JP, Spreeuwenberg C, Van der Linden S. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 419-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695152&dopt=Abstract
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Are prognostic factors in rheumatoid arthritis of any use in daily clinical practice? Author(s): van Riel P. Source: The Netherlands Journal of Medicine. 2002 November; 60(10): 381-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607586&dopt=Abstract
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Arterial stiffness and central blood pressure, as determined by pulse wave analysis, in rheumatoid arthritis. Author(s): Klocke R, Cockcroft JR, Taylor GJ, Hall IR, Blake DR. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 414-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695151&dopt=Abstract
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Assessing the value of rheumatoid arthritis treatment alternatives: the potential effect of tumor necrosis factor inhibitors. Author(s): Mizutani W. Source: Manag Care Interface. 2003 March; 16(3): 44-50, 55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715413&dopt=Abstract
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Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Author(s): Del Rincon I, Williams K, Stern MP, Freeman GL, O'Leary DH, Escalante A. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1833-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847676&dopt=Abstract
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Association of depression and rheumatoid arthritis. Author(s): Dickens C, Jackson J, Tomenson B, Hay E, Creed F. Source: Psychosomatics. 2003 May-June; 44(3): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724502&dopt=Abstract
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Association of mortality with disease severity in rheumatoid arthritis, independent of comorbidity. Author(s): Navarro-Cano G, Del Rincon I, Pogosian S, Roldan JF, Escalante A. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2425-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130461&dopt=Abstract
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Association of polymorphisms of the tumour necrosis factor receptors I and II and rheumatoid arthritis. Author(s): Bayley JP, Bakker AM, Kaijzel EL, Huizinga TW, Verweij CL. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 969-71. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730509&dopt=Abstract
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Association of the -2849 interleukin-10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis. Author(s): Lard LR, van Gaalen FA, Schonkeren JJ, Pieterman EJ, Stoeken G, Vos K, Nelissen RG, Westendorp RG, Hoeben RC, Breedveld FC, Toes RE, Huizinga TW. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1841-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847677&dopt=Abstract
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Atlantoaxial arthrodesis for vertebrobasilar insufficiency due to rheumatoid arthritis: a case report. Author(s): Maekawa T, Sasai K, Iida H, Yamashita K, Sakaida M. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 April; 85-A(4): 711-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672850&dopt=Abstract
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Atlantoaxial disorders in rheumatoid arthritis associate with the destruction of peripheral and shoulder joints, and decreased bone mineral density. Author(s): Neva MH, Kotaniemi A, Kaarela K, Lehtinen JT, Belt EA, Kauppi M. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747271&dopt=Abstract
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Auranofin improves outcome in early rheumatoid arthritis. Results from a 2-year, double blind placebo controlled study. Author(s): Borg G, Allander E, Lund B, Berg E, Brodin U, Pettersson H, Trang L. Source: The Journal of Rheumatology. 1988 December; 15(12): 1747-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14552308&dopt=Abstract
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Autoantibodies can be prognostic markers of an erosive disease in early rheumatoid arthritis. Author(s): Vencovsky J, Machacek S, Sedova L, Kafkova J, Gatterova J, Pesakova V, Ruzickova S. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 427-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695154&dopt=Abstract
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Autoantibodies directed against ribosomal proteins in systemic lupus erythematosus and rheumatoid arthritis: a comparative study. Author(s): Desbos A, Gonzalo P, Monier JC, Tebib J, Reboud JP, Perrier H, Bienvenu J, Fabien N. Source: Autoimmunity. 2002 November; 35(7): 427-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685870&dopt=Abstract
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Autoantigens and immune pathways in rheumatoid arthritis. Author(s): Corrigall VM, Panayi GS. Source: Critical Reviews in Immunology. 2002; 22(4): 281-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678429&dopt=Abstract
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B lymphocytopenia in rheumatoid arthritis is associated with the DRB1 shared epitope and increased acute phase response. Author(s): Wagner U, Kaltenhauser S, Pierer M, Wilke B, Arnold S, Hantzschel H. Source: Arthritis Research. 2002; 4(4): R1. Epub 2002 May 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106500&dopt=Abstract
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Bacterial components in the synovial tissue of patients with advanced rheumatoid arthritis or osteoarthritis: analysis with gas chromatography-mass spectrometry and pan-bacterial polymerase chain reaction. Author(s): Chen T, Rimpilainen M, Luukkainen R, Mottonen T, Yli-Jama T, Jalava J, Vainio O, Toivanen P. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 328-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794787&dopt=Abstract
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Basal levels of DHEAS as a marker for disease activity in premenopausal women with recent onset rheumatoid arthritis. Author(s): Josipovic B, Josipovic A. Source: The Journal of Rheumatology. 2002 August; 29(8): 1803-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180752&dopt=Abstract
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Beneficial effect of being outdoors in rheumatoid arthritis. Author(s): Patberg WR. Source: The Journal of Rheumatology. 2002 January; 29(1): 202-4. Erratum In: J Rheumatol 2002 April; 29(4): 864. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824963&dopt=Abstract
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Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Author(s): Tao X, Younger J, Fan FZ, Wang B, Lipsky PE. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1735-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124856&dopt=Abstract
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Benefit-risk assessment of infliximab in the treatment of rheumatoid arthritis. Author(s): Mikuls TR, Moreland LW. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(1): 23-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495361&dopt=Abstract
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Biaxial total wrist replacement in patients with rheumatoid arthritis. Clinical review, survivorship and radiological analysis. Author(s): Takwale VJ, Nuttall D, Trail IA, Stanley JK. Source: The Journal of Bone and Joint Surgery. British Volume. 2002 July; 84(5): 692-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188487&dopt=Abstract
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Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism. Author(s): Tengstrand B, Carlstrom K, Hafstrom I. Source: Rheumatology (Oxford, England). 2002 March; 41(3): 285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934965&dopt=Abstract
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Biological modifier therapy for the treatment of rheumatoid arthritis. Author(s): Jenkins JK, Hardy KJ. Source: The American Journal of the Medical Sciences. 2002 April; 323(4): 197-205. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003375&dopt=Abstract
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Biological relevance of the polymorphism in the CCR5 gene in refractory and nonrefractory rheumatoid arthritis in Mexicans. Author(s): Zuniga JA, Villarreal-Garza C, Flores E, Barquera R, Perez-Hernandez N, Montes de Oca JV, Cardiel MH, Vargas-Alarcon G, Granados J. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 351-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846056&dopt=Abstract
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Biological response modifiers in rheumatoid arthritis. Author(s): Kassimos D, Mitton D, Whallett A, Delamere JP, Kitas GD. Source: Lancet. 2002 January 26; 359(9303): 352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830225&dopt=Abstract
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Biological response modifiers in the management of rheumatoid arthritis. Author(s): Louie SG, Park B, Yoon H. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 February 15; 60(4): 346-55. Review. Erratum In: Am J Health Syst Pharm.2003 June 1; 60(11): 1095. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625216&dopt=Abstract
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Biologics in the treatment of rheumatoid arthritis: mechanisms of action. Author(s): Kavanaugh A, Lipsky P. Source: Curr Dir Autoimmun. 2001; 3: 240-73. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791469&dopt=Abstract
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BiP, a putative autoantigen in rheumatoid arthritis, stimulates IL-10-producing CD8positive T cells from normal individuals. Author(s): Bodman-Smith MD, Corrigall VM, Kemeny DM, Panayi GS. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 637-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709539&dopt=Abstract
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Bipolar hemiarthroplasty in juvenile rheumatoid arthritis: long-term survivorship and outcomes. Author(s): Yun AG, Martin S, Zurakowski D, Scott R. Source: The Journal of Arthroplasty. 2002 December; 17(8): 978-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478506&dopt=Abstract
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Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Author(s): Abramson SB, Amin A. Source: Rheumatology (Oxford, England). 2002 September; 41(9): 972-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209029&dopt=Abstract
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Blood serotonin and joint pain in seropositive versus seronegative rheumatoid arthritis. Author(s): Kopp S, Alstergren P. Source: Mediators of Inflammation. 2002 August; 11(4): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396472&dopt=Abstract
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Blood TNF-alpha and combination therapy for rheumatoid arthritis. Author(s): Famularo G. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 404. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846067&dopt=Abstract
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Blood transfusion, alcohol use, and anthropometric risk factors for rheumatoid arthritis in older women. Author(s): Cerhan JR, Saag KG, Criswell LA, Merlino LA, Mikuls TR. Source: The Journal of Rheumatology. 2002 February; 29(2): 246-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838841&dopt=Abstract
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Bloodstream thrombopoietin in rheumatoid arthritis with thrombocytosis. Author(s): Kiraz S, Ertenli I, Ozturk MA, Haznedaroglu IC, Celik I, Kirazli S, Calguneri M. Source: Clinical Rheumatology. 2002 November; 21(6): 453-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447626&dopt=Abstract
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B-lymphocyte depletion therapy in rheumatoid arthritis and other autoimmune disorders. Author(s): Edwards JC, Leandro MJ, Cambridge G. Source: Biochemical Society Transactions. 2002 August; 30(4): 824-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196207&dopt=Abstract
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Bone and joint destruction in rheumatoid arthritis: what is really happening? Author(s): Goldring SR. Source: J Rheumatol Suppl. 2002 September; 65: 44-8. Review. Erratum In: J Rheumatol Suppl. 2002 November; 29(11): 2471. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236623&dopt=Abstract
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Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis. Author(s): McQueen FM, Benton N, Perry D, Crabbe J, Robinson E, Yeoman S, McLean L, Stewart N. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1814-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847674&dopt=Abstract
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Bone loss in patients with rheumatoid arthritis: results from a population-based cohort of 366 patients followed up for two years. Author(s): Haugeberg G, Orstavik RE, Uhlig T, Falch JA, Halse JI, Kvien TK. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1720-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124854&dopt=Abstract
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Bone marrow progenitor cell reserve and function and stromal cell function are defective in rheumatoid arthritis: evidence for a tumor necrosis factor alpha-mediated effect. Author(s): Papadaki HA, Kritikos HD, Gemetzi C, Koutala H, Marsh JC, Boumpas DT, Eliopoulos GD. Source: Blood. 2002 March 1; 99(5): 1610-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861275&dopt=Abstract
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Bone metabolism and histomorphometric changes in rheumatoid arthritis. Author(s): Perez-Edo L, Diez-Perez A, Marinoso L, Valles A, Serrano S, Carbonell J. Source: Scandinavian Journal of Rheumatology. 2002; 31(5): 285-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455819&dopt=Abstract
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Bone mineral density in men with rheumatoid arthritis is associated with erosive disease and sulfasalazine treatment but not with sex hormones. Author(s): Tengstrand B, Hafstrom I. Source: The Journal of Rheumatology. 2002 November; 29(11): 2299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415584&dopt=Abstract
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Bone quality and bone mass as assessed by quantitative ultrasound and dual energy x ray absorptiometry in women with rheumatoid arthritis: relationship with quadriceps strength. Author(s): Madsen OR, Sorensen OH, Egsmose C. Source: Annals of the Rheumatic Diseases. 2002 April; 61(4): 325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874835&dopt=Abstract
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Bone resorption and inflammatory inhibition efficacy of intermittent cyclical etidronate therapy in rheumatoid arthritis. Author(s): Hasegawa J, Nagashima M, Yamamoto M, Nishijima T, Katsumata S, Yoshino S. Source: The Journal of Rheumatology. 2003 March; 30(3): 474-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610804&dopt=Abstract
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Brain abscess in rheumatoid arthritis. Author(s): Lee CS, Chang CK. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 689-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810444&dopt=Abstract
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Brief report: adjustment to juvenile rheumatoid arthritis: a family systems perspective. Author(s): Helgeson VS, Janicki D, Lerner J, Barbarin O. Source: Journal of Pediatric Psychology. 2003 July-August; 28(5): 347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808011&dopt=Abstract
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Brief report: child-rearing practices of caregivers with and without a child with juvenile rheumatoid arthritis: perspectives of caregivers and professionals. Author(s): Gerhardt CA, Vannatta K, McKellop JM, Taylor J, Passo M, Reiter-Purtill J, Zeller M, Noll RB. Source: Journal of Pediatric Psychology. 2003 June; 28(4): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730284&dopt=Abstract
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Bronchiolitis obliterans in a case of juvenile rheumatoid arthritis presented with pneumomediastinum. Author(s): Dikensoy O, Bayram N, Bingol A, Filiz A. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(1): 100-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844973&dopt=Abstract
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Bullous skin lesions following infliximab infusion in a patient with rheumatoid arthritis. Author(s): Kent PD, Davis JM 3rd, Davis MD, Matteson EL. Source: Arthritis and Rheumatism. 2002 August; 46(8): 2257-8; Author Reply 2259. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209539&dopt=Abstract
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By the way, doctor. I've heard about a new rheumatoid arthritis drug that I'd only have to take every two weeks. What do you know about it? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2003 May; 10(9): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763730&dopt=Abstract
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Calciphylaxis in a patient with rheumatoid arthritis without renal failure and hyperparathyroidism: the possible role of long-term steroid use and protein S deficiency. Author(s): Korkmaz C, Dundar E, Zubaroglu I. Source: Clinical Rheumatology. 2002 February; 21(1): 66-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954890&dopt=Abstract
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Can hepatitis C virus infection and interferon-alpha undo the HLADRB1*0402/DQB1*0302 protection against rheumatoid arthritis? Author(s): La Civita L, Fadda P, Gaudiano C, Bentivenga C, Olivieri I. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595642&dopt=Abstract
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Can progression of radiographic joint damage be predicted early in rheumatoid arthritis? Author(s): Voskuyl AE, Boers M. Source: The Journal of Rheumatology. 2003 May; 30(5): 905-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734879&dopt=Abstract
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Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Author(s): Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC. Source: Circulation. 2003 March 11; 107(9): 1303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628952&dopt=Abstract
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Carpal tunnel syndrome grading system in rheumatoid arthritis. Author(s): Shinoda J, Hashizume H, McCown C, Senda M, Nishida K, Doi T, Inoue H. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(2): 188-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956978&dopt=Abstract
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Cartilage destruction mediated by synovial fibroblasts does not depend on proliferation in rheumatoid arthritis. Author(s): Seemayer CA, Kuchen S, Kuenzler P, Rihoskova V, Rethage J, Aicher WK, Michel BA, Gay RE, Kyburz D, Neidhart M, Gay S. Source: American Journal of Pathology. 2003 May; 162(5): 1549-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707039&dopt=Abstract
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Case number 26: massive cholesterol crystal deposition: unusual location in rheumatoid arthritis. Author(s): Balint PV, Kane D, Sturrock RD. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 512. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759285&dopt=Abstract
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Cases of early inflammatory polyarthritis should not be classified as having rheumatoid arthritis. Author(s): Symmons DP, Hazes JM, Silman AJ. Source: The Journal of Rheumatology. 2003 May; 30(5): 902-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734878&dopt=Abstract
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CD34-selected versus unmanipulated grafts for severe rheumatoid arthritis: comment on the article by Moore et al. Author(s): Van Laar JM, Pavletic SZ. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1463-4; Author Reply 1464-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746925&dopt=Abstract
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CD44 in rheumatoid arthritis. Author(s): Naor D, Nedvetzki S. Source: Arthritis Research & Therapy. 2003; 5(3): 105-15. Epub 2003 February 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723975&dopt=Abstract
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Celecoxib for rheumatoid arthritis. Author(s): Garner S, Fidan D, Frankish R, Judd M, Shea B, Towheed T, Wells G, Tugwell P. Source: Cochrane Database Syst Rev. 2002; (4): Cd003831. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519610&dopt=Abstract
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Cemented ceramic YMCK total knee arthroplasty in patients with severe rheumatoid arthritis. Author(s): Koshino T, Okamoto R, Takagi T, Yamamoto K, Saito T. Source: The Journal of Arthroplasty. 2002 December; 17(8): 1009-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478511&dopt=Abstract
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Cementless acetabular replacement in patients with rheumatoid arthritis: a 6- to 14year prospective study. Author(s): Katsimihas M, Taylor AH, Lee MB, Sarangi PP, Learmonth ID. Source: The Journal of Arthroplasty. 2003 January; 18(1): 16-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555177&dopt=Abstract
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Cervical spine disease in rheumatoid arthritis: how common a finding? How uncommon a problem? Author(s): Matteson EL. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1775-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847668&dopt=Abstract
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Changes in self-efficacy and health status over 5 years: a longitudinal observational study of 306 patients with rheumatoid arthritis. Author(s): Brekke M, Hjortdahl P, Kvien TK. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 342-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794789&dopt=Abstract
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Characterisation of the cell type-specificity of collagenase 3 mRNA expression in comparison with membrane type 1 matrix metalloproteinase and gelatinase A in the synovial membrane in rheumatoid arthritis. Author(s): Petrow PK, Wernicke D, Schulze Westhoff C, Hummel KM, Brauer R, Kriegsmann J, Gromnica-Ihle E, Gay RE, Gay S. Source: Annals of the Rheumatic Diseases. 2002 May; 61(5): 391-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959761&dopt=Abstract
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Chemokine blockade and chronic inflammatory disease: proof of concept in patients with rheumatoid arthritis. Author(s): Haringman JJ, Kraan MC, Smeets TJ, Zwinderman KH, Tak PP. Source: Annals of the Rheumatic Diseases. 2003 August; 62(8): 715-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860725&dopt=Abstract
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Chemokines and chemokine receptors in rheumatoid arthritis. Author(s): Szekanecz Z, Kim J, Koch AE. Source: Seminars in Immunology. 2003 February; 15(1): 15-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495637&dopt=Abstract
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Chronic pulmonary toxicity of methotrexate and rheumatoid arthritis. Author(s): Provenzano G. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 802-3; Author Reply 803-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771440&dopt=Abstract
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Cigarette smoking and severity of rheumatoid arthritis. Author(s): Hutchinson D, Moots R. Source: Rheumatology (Oxford, England). 2001 December; 40(12): 1426-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752525&dopt=Abstract
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Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women's Health Study. Author(s): Criswell LA, Merlino LA, Cerhan JR, Mikuls TR, Mudano AS, Burma M, Folsom AR, Saag KG. Source: The American Journal of Medicine. 2002 April 15; 112(6): 465-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959057&dopt=Abstract
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Clinical and psychological outcome from a randomized controlled trial of patientinitiated direct-access hospital follow-up for rheumatoid arthritis extended to 4 years. Author(s): Kirwan JR, Mitchell K, Hewlett S, Hehir M, Pollock J, Memel D, Bennett B. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 422-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626791&dopt=Abstract
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Clinical and radiological effects of anakinra in patients with rheumatoid arthritis. Author(s): Bresnihan B, Cobby M. Source: Rheumatology (Oxford, England). 2003 May; 42 Suppl 2: Ii22-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817092&dopt=Abstract
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Clinical features of patients with systemic sclerosis accompanied by rheumatoid arthritis. Author(s): Jinnin M, Ihn H, Yamane K, Asano Y, Yazawa N, Tamaki K. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673896&dopt=Abstract
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Clinical relevance of peripheral vascular occlusive disease in patients with rheumatoid arthritis and systemic lupus erythematosus. Author(s): Henke PK, Sukheepod P, Proctor MC, Upchurch GR Jr, Stanley JC. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 July; 38(1): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844099&dopt=Abstract
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Clonal analysis of B cells in the synovial membrane of patients with rheumatoid arthritis. Author(s): Shiokawa S, Matsumato N, Nishimura J. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635940&dopt=Abstract
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Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements. Author(s): Wagner U, Pierer M, Kaltenhauser S, Wilke B, Seidel W, Arnold S, Hantzschel H. Source: European Journal of Immunology. 2003 January; 33(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594835&dopt=Abstract
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Combined oral cyclosporin and methotrexate therapy in patients with rheumatoid arthritis elevates methotrexate levels and reduces 7-hydroxymethotrexate levels when compared with methotrexate alone. Author(s): Fox RI, Morgan SL, Smith HT, Robbins BA, Choc MG, Baggott JE. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 989-94. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730515&dopt=Abstract
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Comment on methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis. Author(s): Courtney PA, Alderdice J, Whitehead EM. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 617; Author Reply 617-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910574&dopt=Abstract
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Comparative responsiveness of four elbow scoring instruments in patients with rheumatoid arthritis. Author(s): de Boer YA, Hazes JM, Winia PC, Brand R, Rozing PM. Source: The Journal of Rheumatology. 2001 December; 28(12): 2616-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764206&dopt=Abstract
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Comparative study between thromboembolism and total knee arthroplasty with or without tourniquet in rheumatoid arthritis patients. Author(s): Wauke K, Nagashima M, Kato N, Ogawa R, Yoshino S. Source: Archives of Orthopaedic and Trauma Surgery. 2002 November; 122(8): 442-6. Epub 2002 April 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12442180&dopt=Abstract
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Comparing parental distress, family functioning, and the role of social support for caregivers with and without a child with juvenile rheumatoid arthritis. Author(s): Gerhardt CA, Vannatta K, McKellop JM, Zeller M, Taylor J, Passo M, Noll RB. Source: Journal of Pediatric Psychology. 2003 January-February; 28(1): 5-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490626&dopt=Abstract
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Comparison between women and men with recent onset rheumatoid arthritis of disease activity and functional ability over two years (the TIRA project). Author(s): Hallert E, Thyberg I, Hass U, Skargren E, Skogh T. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 667-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810432&dopt=Abstract
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Comparison of synovial MMP-1 and TIMP-1 levels in patients with various inflammatory arthritides: is there any difference between rheumatoid arthritis, Behcet's disease and familial Mediterranean fever? Author(s): Pay S, Erdem H, Serdar M, Dinc A, Simsek I, Turan M. Source: Clinical Rheumatology. 2002 November; 21(6): 511-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447637&dopt=Abstract
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Confronting life with rheumatoid arthritis. Author(s): Melanson PM, Downe-Wamboldt B. Source: Journal of Advanced Nursing. 2003 April; 42(2): 125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670381&dopt=Abstract
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Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis. Author(s): Singh G, Miller JD, Huse DM, Pettitt D, D'Agostino RB, Russell MW. Source: The Journal of Rheumatology. 2003 April; 30(4): 714-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672188&dopt=Abstract
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Contemporary disease modifying antirheumatic drugs (DMARD) in patients with recent onset rheumatoid arthritis in a US private practice: methotrexate as the anchor drug in 90% and new DMARD in 30% of patients. Author(s): Sokka T, Pincus T. Source: The Journal of Rheumatology. 2002 December; 29(12): 2521-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465145&dopt=Abstract
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Contrast-enhanced power Doppler ultrasonography of the metacarpophalangeal joints in rheumatoid arthritis. Author(s): Szkudlarek M, Court-Payen M, Strandberg C, Klarlund M, Klausen T, Ostergaard M. Source: European Radiology. 2003 January; 13(1): 163-8. Epub 2002 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12541125&dopt=Abstract
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Contribution of patient related differences to multidrug resistance in rheumatoid arthritis. Author(s): Morgan C, Lunt M, Brightwell H, Bradburn P, Fallow W, Lay M, Silman A, Bruce IN. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 15-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480663&dopt=Abstract
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Control perceptions in patients with rheumatoid arthritis: the impact of the medical consultation. Author(s): Ryan S, Hassell A, Dawes P, Kendall S. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509626&dopt=Abstract
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Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis. Author(s): Silverio Amancio OM, Alves Chaud DM, Yanaguibashi G, Esteves Hilario MO. Source: European Journal of Clinical Nutrition. 2003 May; 57(5): 706-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771972&dopt=Abstract
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Correlation among macrophage inflammatory protein 1alpha levels, matrix metalloproteinase 8 levels, and systemic inflammation in rheumatoid arthritis: comment on the articles by Yamanaka et al and Mattey et al. Author(s): Kullich WC, Klein G. Source: Arthritis and Rheumatism. 2001 December; 44(12): 2940-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762959&dopt=Abstract
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Correlation of serum levels of adenosine deaminase activity and its isoenzymes with disease activity in rheumatoid arthritis. Author(s): Sari RA, Taysi S, Yilmaz O, Bakan N. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 87-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673895&dopt=Abstract
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Correlation of single time-point damage scores with observed progression of radiographic damage during the first 6 years of rheumatoid arthritis. Author(s): Paulus HE, Oh M, Sharp JT, Gold RH, Wong WK, Park GS, Bulpitt KJ; Western Consortium of Praticing Rheumatologists. Source: The Journal of Rheumatology. 2003 April; 30(4): 705-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672187&dopt=Abstract
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Corticotropin-releasing hormone promoter polymorphisms in patients with rheumatoid arthritis from northwest Spain. Author(s): Gonzalez-Gay MA, Hajeer AH, Garcia-Porrua C, Dababneh A, Amoli MM, Botana MA, Thomson W, Llorca J, Ollier WE. Source: The Journal of Rheumatology. 2003 May; 30(5): 913-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734882&dopt=Abstract
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Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis. Author(s): Rovensky J, Imrich R, Koska J, Kovalancik M, Killinger Z, Payer J, Vigas M, Jezova D. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 674-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810434&dopt=Abstract
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Cost effectiveness and cost utility analysis of multidisciplinary care in patients with rheumatoid arthritis: a randomised comparison of clinical nurse specialist care, inpatient team care, and day patient team care. Author(s): van den Hout WB, Tijhuis GJ, Hazes JM, Breedveld FC, Vliet Vlieland TP. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 308-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634227&dopt=Abstract
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Cost effectiveness of adding leflunomide to a 5-year strategy of conventional diseasemodifying antirheumatic drugs in patients with rheumatoid arthritis. Author(s): Maetzel A, Strand V, Tugwell P, Wells G, Bombardier C. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 655-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522841&dopt=Abstract
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Cost-effectiveness of low dose corticosteroids versus non-steroidal anti-inflammatory drugs and COX-2 specific inhibitors in the long-term treatment of rheumatoid arthritis. Author(s): Bae SC, Corzillius M, Kuntz KM, Liang MH. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 46-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509612&dopt=Abstract
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Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. Author(s): Dong H, Strome SE, Matteson EL, Moder KG, Flies DB, Zhu G, Tamura H, Driscoll CL, Chen L. Source: The Journal of Clinical Investigation. 2003 February; 111(3): 363-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569162&dopt=Abstract
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Costs and predictors of costs in rheumatoid arthritis: a prevalence-based study. Author(s): Lajas C, Abasolo L, Bellajdel B, Hernandez-Garcia C, Carmona L, Vargas E, Lazaro P, Jover JA. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 64-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579595&dopt=Abstract
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Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer's data sources. Author(s): Ruof J, Hulsemann JL, Mittendorf T, Handelmann S, von der Schulenburg JM, Zeidler H, Merkesdal S. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 544-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759292&dopt=Abstract
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Course of radiographic damage over 10 years in a cohort with early rheumatoid arthritis. Author(s): Lindqvist E, Jonsson K, Saxne T, Eberhardt K. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 611-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810421&dopt=Abstract
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Craniocervical fusion for rheumatoid arthritis: comparison of sublaminar wires and the lateral mass screw craniocervical fusion. Author(s): Shad A, Shariff SS, Teddy PJ, Cadoux-Hudson TA. Source: British Journal of Neurosurgery. 2002 October; 16(5): 483-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498493&dopt=Abstract
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Current drug therapy for rheumatoid arthritis. Author(s): Kawai S. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(2): 259-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665969&dopt=Abstract
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Cyclosporin A monotherapy versus cyclosporin A and methotrexate combination therapy in patients with early rheumatoid arthritis: a double blind randomised placebo controlled trial. Author(s): Gerards AH, Landewe RB, Prins AP, Bruijn GA, Goei The HS, Laan RF, Dijkmans BA. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634224&dopt=Abstract
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Cytokines in the pathogenesis of rheumatoid arthritis and collagen-induced arthritis. Author(s): Lubberts E, van den Berg WB. Source: Advances in Experimental Medicine and Biology. 2003; 520: 194-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613579&dopt=Abstract
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Cytotoxicity responses to peptide antigens in rheumatoid arthritis and ankylosing spondylitis. Author(s): Wilson C, Rashid T, Tiwana H, Beyan H, Hughes L, Bansal S, Ebringer A, Binder A. Source: The Journal of Rheumatology. 2003 May; 30(5): 972-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734891&dopt=Abstract
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Declining use of orthopedic surgery in patients with rheumatoid arthritis? Results of a long-term, population-based assessment. Author(s): da Silva E, Doran MF, Crowson CS, O'Fallon WM, Matteson EL. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687513&dopt=Abstract
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Decreased catecholamine-induced cell death in B lymphocytes from patients with rheumatoid arthritis. Author(s): Wahle M, Pierer M, Krause A, Kolker S, Baerwald CG. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 425-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114300&dopt=Abstract
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Decreased flares of rheumatoid arthritis during the first year of etanercept treatment: further evidence of clinical effectiveness in the “real world”. Author(s): Yazici Y, Erkan D, Kulman I, Belostocki K, Harrison MJ. Source: Annals of the Rheumatic Diseases. 2002 July; 61(7): 638-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079908&dopt=Abstract
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Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964-95. Author(s): Bjornadal L, Baecklund E, Yin L, Granath F, Klareskog L, Ekbom A. Source: The Journal of Rheumatology. 2002 May; 29(5): 906-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022348&dopt=Abstract
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Decreasing pain and depression in a health promotion program for people with rheumatoid arthritis. Author(s): Oh H, Seo W. Source: Journal of Nursing Scholarship : an Official Publication of Sigma Theta Tau International Honor Society of Nursing / Sigma Theta Tau. 2003; 35(2): 127-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854292&dopt=Abstract
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Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Author(s): Mottonen T, Hannonen P, Korpela M, Nissila M, Kautiainen H, Ilonen J, Laasonen L, Kaipiainen-Seppanen O, Franzen P, Helve T, Koski J, GripenbergGahmberg M, Myllykangas-Luosujarvi R, Leirisalo-Repo M; FIN-RACo Trial Group. FINnish Rheumatoid Arthritis Combination therapy. Source: Arthritis and Rheumatism. 2002 April; 46(4): 894-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953964&dopt=Abstract
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Delayed neutrophil apoptosis induced by synovial fluid in rheumatoid arthritis: role of cytokines, estrogens, and adenosine. Author(s): Ottonello L, Frumento G, Arduino N, Bertolotto M, Mancini M, Sottofattori E, Dallegri F, Cutolo M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114276&dopt=Abstract
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Dentition status and temporomandibular joint disorders in patients with rheumatoid arthritis. Author(s): Yamakawa M, Ansai T, Kasai S, Ohmaru T, Takeuchi H, Kawaguchi T, Takehara T. Source: Cranio. 2002 July; 20(3): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150262&dopt=Abstract
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Deriving an operational definition of low disease activity state in rheumatoid arthritis. Author(s): Boers M, Anderson JJ, Felson DT. Source: The Journal of Rheumatology. 2003 May; 30(5): 1112-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734919&dopt=Abstract
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Dermatological complications of etanercept therapy for rheumatoid arthritis. Author(s): Misery L, Perrot JL, Gentil-Perret A, Pallot-Prades B, Cambazard F, Alexandre C. Source: The British Journal of Dermatology. 2002 February; 146(2): 334-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903255&dopt=Abstract
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Detecting radiological changes in rheumatoid arthritis that are considered important by clinical experts: influence of reading with or without known sequence. Author(s): Bruynesteyn K, Van Der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, Houben H, Griffiths B, Edmonds J, Bresnihan B, Boonen A, Van Der Linden S. Source: The Journal of Rheumatology. 2002 November; 29(11): 2306-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415585&dopt=Abstract
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Detection and monitoring of methotrexate-associated lung injury using serum markers KL-6 and SP-D in rheumatoid arthritis. Author(s): Miyata M, Sakuma F, Fukaya E, Kobayashi H, Rai T, Saito H, Kasukawa R, Suzuki S. Source: Intern Med. 2002 June; 41(6): 467-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135181&dopt=Abstract
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Detection of antibodies to deiminated recombinant rat filaggrin by enzyme-linked immunosorbent assay: a highly effective test for the diagnosis of rheumatoid arthritis. Author(s): Vincent C, Nogueira L, Sebbag M, Chapuy-Regaud S, Arnaud M, Letourneur O, Rolland D, Fournie B, Cantagrel A, Jolivet M, Serre G. Source: Arthritis and Rheumatism. 2002 August; 46(8): 2051-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209508&dopt=Abstract
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Detection of oncofetal h19 RNA in rheumatoid arthritis synovial tissue. Author(s): Stuhlmuller B, Kunisch E, Franz J, Martinez-Gamboa L, Hernandez MM, Pruss A, Ulbrich N, Erdmann VA, Burmester GR, Kinne RW. Source: American Journal of Pathology. 2003 September; 163(3): 901-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937131&dopt=Abstract
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Determinants of physical function in rheumatoid arthritis: association with the disease process. Author(s): Hazes JM. Source: Rheumatology (Oxford, England). 2003 May; 42 Suppl 2: Ii17-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817091&dopt=Abstract
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Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable difference. Author(s): Bruynesteyn K, van der Heijde D, Boers M, Saudan A, Peloso P, Paulus H, Houben H, Griffiths B, Edmonds J, Bresnihan B, Boonen A, van der Linden S. Source: Arthritis and Rheumatism. 2002 April; 46(4): 913-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953967&dopt=Abstract
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Development and clinical application of COX-2-selective inhibitors for the treatment of osteoarthritis and rheumatoid arthritis. Author(s): Bingham CO 3rd. Source: Cleve Clin J Med. 2002; 69 Suppl 1: Si5-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086294&dopt=Abstract
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Development of a new instrument for rheumatoid arthritis: the Cedars-Sinai HealthRelated Quality of Life instrument (CSHQ-RA). Author(s): Weisman MH, Paulus HE, Russak SM, Lubeck DP, Chiou CF, Sengupta N, Ofman JJ, Borenstein J, Moadel AB, Sherbourne CD. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 78-84. Erratum In: Arthritis Rheum. 2003 June 15; 49(3): 477. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579597&dopt=Abstract
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Development of a work instability scale for rheumatoid arthritis. Author(s): Gilworth G, Chamberlain MA, Harvey A, Woodhouse A, Smith J, Smyth MG, Tennant A. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794790&dopt=Abstract
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Development of an instrument to measure disability in parenting activity among women with rheumatoid arthritis. Author(s): Katz PP, Pasch LA, Wong B. Source: Arthritis and Rheumatism. 2003 April; 48(4): 935-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687535&dopt=Abstract
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Development of anti-TNF therapy for rheumatoid arthritis. Author(s): Feldmann M. Source: Nature Reviews. Immunology. 2002 May; 2(5): 364-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033742&dopt=Abstract
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Development of rheumatoid arthritis following autologous peripheral blood stem cell transplantation. Author(s): Imamura R, Inoue H, Kato K, Kobayashi S, Tsukamoto H, Nagafuji K, Shimoda K, Nakashima H, Otsuka T, Gondo H, Harada M. Source: Bone Marrow Transplantation. 2002 October; 30(8): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379893&dopt=Abstract
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Development of rheumatoid arthritis is not associated with two polymorphisms in the Crohn's disease gene CARD15. Author(s): Steer S, Fisher SA, Fife M, Cuthbert A, Newton J, Wordsworth P, Lewis CM, Mathew CG, Lanchbury JS. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 304-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595627&dopt=Abstract
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Diagnosing early-onset rheumatoid arthritis: the role of anti-CCP antibodies. Author(s): Vasishta A. Source: Am Clin Lab. 2002 August-September; 21(7): 34-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380030&dopt=Abstract
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Diagnostic significance of increased serum hyaluronic acid in juvenile rheumatoid arthritis. Author(s): Shigemori M, Takei S, Imanaka H, Maeno N, Hokonohara M, Miyata K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 August; 44(4): 394-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139564&dopt=Abstract
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Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors. Author(s): Bas S, Perneger TV, Seitz M, Tiercy JM, Roux-Lombard P, Guerne PA. Source: Rheumatology (Oxford, England). 2002 July; 41(7): 809-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096232&dopt=Abstract
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Diagnostic value of high-resolution B-mode and doppler sonography for imaging of hand and finger joints in rheumatoid arthritis. Author(s): Weidekamm C, Koller M, Weber M, Kainberger F. Source: Arthritis and Rheumatism. 2003 February; 48(2): 325-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571840&dopt=Abstract
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Diagnostic value of radiographs of the hands and feet in early rheumatoid arthritis. Author(s): Devauchelle-Pensec V, Saraux A, Alapetite S, Colin D, Le Goff P. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 October; 69(5): 434-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477226&dopt=Abstract
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Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthritis. Author(s): Nakamura H, Hishinuma T, Suzuki N, Chiba S, Tsukamoto H, Takabatake M, Sawai T, Mitomo T, Inoue H, Matsumoto F, Mizugaki M. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2001 NovemberDecember; 65(5-6): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993724&dopt=Abstract
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Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis. Author(s): Muzaffer MA, Dayer JM, Feldman BM, Pruzanski W, Roux-Lombard P, Schneider R, Laxer RM, Silverman ED. Source: The Journal of Rheumatology. 2002 May; 29(5): 1071-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022325&dopt=Abstract
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Differences in understanding and application of 1987 ACR criteria for rheumatoid arthritis and 1991 ESSG criteria for spondylarthropathy. A pilot survey. Author(s): Berthelot JM, Bernelot-Moens HJ, Klarlund M, McGonagle D, Calin A, Schumacher HR, Combe B, De Bandt M, Drosos AA, Flipo RM, Harris BJ, Kaarela K, Le Goff P, Meyer O, Punzi L, Zerbini CA, Saraux A; CRI Group. Source: Clin Exp Rheumatol. 2002 March-April; 20(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051392&dopt=Abstract
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Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. Author(s): Tsark EC, Wang W, Teng YC, Arkfeld D, Dodge GR, Kovats S. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 December 1; 169(11): 662533. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444176&dopt=Abstract
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Differing effects of methylenetetrahydrofolate reductase single nucleotide polymorphisms on methotrexate efficacy and toxicity in rheumatoid arthritis. Author(s): Evans WE. Source: Pharmacogenetics. 2002 April; 12(3): 181-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927832&dopt=Abstract
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Dipeptidyl peptidase IV on activated T cells as a target molecule for therapy of rheumatoid arthritis. Author(s): Williams YN, Baba H, Hayashi S, Ikai H, Sugita T, Tanaka S, Miyasaka N, Kubota T. Source: Clinical and Experimental Immunology. 2003 January; 131(1): 68-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519388&dopt=Abstract
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Disease activity and health status in rheumatoid arthritis: a case-control comparison between Norway and Lithuania. Author(s): Dadoniene J, Uhlig T, Stropuviene S, Venalis A, Boonen A, Kvien TK. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594108&dopt=Abstract
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Disease activity in rheumatoid arthritis: fibrinogen is superior to the erythrocyte sedimentation rate. Author(s): Arvidson NG, Larsson A, Larsen A. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2002; 62(4): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476931&dopt=Abstract
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Disease course and outcome of juvenile rheumatoid arthritis in a multicenter cohort. Author(s): Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Cheang M. Source: The Journal of Rheumatology. 2002 September; 29(9): 1989-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233897&dopt=Abstract
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Dissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritis. Author(s): Jawaheer D, Li W, Graham RR, Chen W, Damle A, Xiao X, Monteiro J, Khalili H, Lee A, Lundsten R, Begovich A, Bugawan T, Erlich H, Elder JT, Criswell LA, Seldin MF, Amos CI, Behrens TW, Gregersen PK. Source: American Journal of Human Genetics. 2002 September; 71(3): 585-94. Epub 2002 August 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181776&dopt=Abstract
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Disseminated cryptococcal infection in rheumatoid arthritis treated with methotrexate and infliximab. Author(s): True DG, Penmetcha M, Peckham SJ. Source: The Journal of Rheumatology. 2002 July; 29(7): 1561-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136922&dopt=Abstract
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Distribution of protein nitrotyrosine in synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Author(s): Sandhu JK, Robertson S, Birnboim HC, Goldstein R. Source: The Journal of Rheumatology. 2003 June; 30(6): 1173-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784386&dopt=Abstract
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Disturbed grip function in women with rheumatoid arthritis. Author(s): Dellhag B, Hosseini N, Bremell T, Ingvarsson PE. Source: The Journal of Rheumatology. 2001 December; 28(12): 2624-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764207&dopt=Abstract
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Does activation of the innate immune system contribute to the development of rheumatoid arthritis? Author(s): Klinman D. Source: Arthritis and Rheumatism. 2003 March; 48(3): 590-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632408&dopt=Abstract
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Does active treatment of rheumatoid arthritis limit disease-associated bone loss? Author(s): Dolan AL, Moniz C, Abraha H, Pitt P. Source: Rheumatology (Oxford, England). 2002 September; 41(9): 1047-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209040&dopt=Abstract
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Does concomitant osteoarthritis affect histopathologic changes in patients with rheumatoid arthritis? Comment on the article by Kraan et al. Author(s): Wei N. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1161; Author Reply 1162. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687564&dopt=Abstract
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Does vascular endothelial growth factor play a role in interleukin-6 receptor antagonist therapy for rheumatoid arthritis? Author(s): Gentiletti J, Fava RA. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1471-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794810&dopt=Abstract
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Does yttrium radiosynovectomy increase the risk of cancer in patients with rheumatoid arthritis? Author(s): Vuorela J, Sokka T, Pukkala E, Hannonen P. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594113&dopt=Abstract
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Doppler sonographic findings in the long bicipital tendon sheath in patients with rheumatoid arthritis as compared with patients with degenerative diseases of the shoulder. Author(s): Strunk J, Lange U, Kurten B, Schmidt KL, Neeck G. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1828-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847675&dopt=Abstract
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Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: a comparative study. Author(s): Terslev L, Torp-Pedersen S, Savnik A, von der Recke P, Qvistgaard E, Danneskiold-Samsoe B, Bliddal H. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2434-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130462&dopt=Abstract
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Dose response and safety study of meloxicam up to 22.5 mg daily in rheumatoid arthritis: a 12 week multicenter, double blind, dose response study versus placebo and diclofenac. Author(s): Furst DE, Kolba KS, Fleischmann R, Silverfield J, Greenwald M, Roth S, Hall DB, Roszko PJ; Meloxicam Rheumatoid Arthritis Investigators. Source: The Journal of Rheumatology. 2002 March; 29(3): 436-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908554&dopt=Abstract
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Dose titration using the Disease Activity Score (DAS28) in rheumatoid arthritis patients treated with anti-TNF-alpha. Author(s): Den Broeder AA, Creemers MC, van Gestel AM, van Riel PL. Source: Rheumatology (Oxford, England). 2002 June; 41(6): 638-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048289&dopt=Abstract
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Down regulation of glucocorticoid receptors in early-diagnosed rheumatoid arthritis. Author(s): van Everdingen AA, Huisman AM, Wenting MJ, van Reesema S, Jacobs JW, Bijlsma JW. Source: Clin Exp Rheumatol. 2002 July-August; 20(4): 463-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175100&dopt=Abstract
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Downregulation of a rheumatoid arthritis-related antigen (RA-A47) by ra-a47 antisense oligonucleotides induces inflammatory factors in chondrocytes. Author(s): Hattori T, Kawaki H, Kubota S, Yutani Y, de Crombrugghe B, von der Mark K, Takigawa M. Source: Journal of Cellular Physiology. 2003 October; 197(1): 94-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942545&dopt=Abstract
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DRB1*04 subtype in Thai patients with rheumatoid arthritis. Author(s): Pimtanothai N, Kimkong I, Inwattana R, Deesomchok U, Charoenwongse P. Source: J Med Assoc Thai. 2002 June; 85 Suppl 1: S366-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188437&dopt=Abstract
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Drug development in rheumatoid arthritis. Author(s): Witter J. Source: Current Opinion in Rheumatology. 2002 May; 14(3): 276-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981326&dopt=Abstract
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Drug survival, efficacy and toxicity of monotherapy with a fully human anti-tumour necrosis factor-alpha antibody compared with methotrexate in long-standing rheumatoid arthritis. Author(s): Barrera P, van der Maas A, van Ede AE, Kiemeney BA, Laan RF, van de Putte LB, van Riel PL. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 430-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961174&dopt=Abstract
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Drug-induced lupus following treatment with infliximab in rheumatoid arthritis. Author(s): Favalli EG, Sinigaglia L, Varenna M, Arnoldi C. Source: Lupus. 2002; 11(11): 753-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475006&dopt=Abstract
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Dynamic gadolinium-enhanced magnetic resonance imaging of the wrist in patients with rheumatoid arthritis can discriminate active from inactive disease. Author(s): Cimmino MA, Innocenti S, Livrone F, Magnaguagno F, Silvestri E, Garlaschi G. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746893&dopt=Abstract
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Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis: effects of treatment with cyclosporin A (Neoral). Author(s): VanderBorght A, De Keyser F, Geusens P, De Backer M, Malaise M, Baeten D, Van den Bosch F, Veys EM, Raus J, Stinissen P. Source: The Journal of Rheumatology. 2002 March; 29(3): 416-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908552&dopt=Abstract
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Dysphagia in a patient with rheumatoid arthritis and iron deficiency anemia. Author(s): Medrano M. Source: Medgenmed [electronic Resource] : Medscape General Medicine. 2002 August 28; 4(3): 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466753&dopt=Abstract
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Dysregulated lymphocyte proliferation and differentiation in patients with rheumatoid arthritis. Author(s): Ponchel F, Morgan AW, Bingham SJ, Quinn M, Buch M, Verburg RJ, Henwood J, Douglas SH, Masurel A, Conaghan P, Gesinde M, Taylor J, Markham AF, Emery P, van Laar JM, Isaacs JD. Source: Blood. 2002 December 15; 100(13): 4550-6. Epub 2002 August 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393721&dopt=Abstract
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Early and extensive erosiveness in peripheral joints predicts atlantoaxial subluxations in patients with rheumatoid arthritis. Author(s): Neva MH, Isomaki P, Hannonen P, Kauppi M, Krishnan E, Sokka T. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1808-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847673&dopt=Abstract
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Early predictors of longterm outcome in patients with juvenile rheumatoid arthritis: subset-specific correlations. Author(s): Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Reed M, Schroeder ML, Cheang M. Source: The Journal of Rheumatology. 2003 March; 30(3): 585-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610821&dopt=Abstract
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Early rheumatoid arthritis patients: relationship of age. Author(s): Papadopoulos IA, Katsimbri P, Alamanos Y, Voulgari PV, Drosos AA. Source: Rheumatology International. 2003 March; 23(2): 70-4. Epub 2002 October 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634939&dopt=Abstract
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Economic evaluation of programs or interventions in the management of rheumatoid arthritis: defining a consensus-based reference case. Author(s): Maetzel A, Tugwell P, Boers M, Guillemin F, Coyle D, Drummond M, Wong JB, Gabriel SE; OMERACT 6 Economics Research Group. Source: The Journal of Rheumatology. 2003 April; 30(4): 891-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672224&dopt=Abstract
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Effect of caffeine consumption on efficacy of methotrexate in rheumatoid arthritis. Author(s): Nesher G, Mates M, Zevin S. Source: Arthritis and Rheumatism. 2003 February; 48(2): 571-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571869&dopt=Abstract
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Effect of cyclical intermittent etidronate therapy on circulating osteoprotegerin levels in patients with rheumatoid arthritis. Author(s): Valleala H, Mandelin J, Laasonen L, Koivula MK, Risteli J, Konttinen YT. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 May; 148(5): 527-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12720535&dopt=Abstract
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Effect of valued activity disability, social comparisons, and satisfaction with ability on depressive symptoms in rheumatoid arthritis. Author(s): Neugebauer A, Katz PP, Pasch LA. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2003 May; 22(3): 253-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790252&dopt=Abstract
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Effectiveness of a measurement feedback system on outcome in rheumatoid arthritis: a controlled clinical trial. Author(s): Fransen J, Stucki G, Twisk J, Chamot AM, Gerster JC, Langenegger T, Seitz M, Michel BA; mebers of the Swiss Clinical Quality Management in Rheumatoid Arthritis (SCQM). Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 624-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810423&dopt=Abstract
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Effects of anakinra on clinical and radiological outcomes in rheumatoid arthritis. Author(s): Bresnihan B. Source: Annals of the Rheumatic Diseases. 2002 November; 61 Suppl 2: Ii74-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379629&dopt=Abstract
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Effects of disease management programs on functional status of patients with rheumatoid arthritis. Author(s): Badamgarav E, Croft JD Jr, Hohlbauch A, Louie JS, O'Dell J, Ofman JJ, Suarez-Almazor ME, Weaver A, White P, Katz P; Evidence-Based Medicine Working Groups in Rheumatology. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 377-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794794&dopt=Abstract
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Effects of dynamic strength training on physical function, Valpar 9 work sample test, and working capacity in patients with recent-onset rheumatoid arthritis. Author(s): Hakkinen A, Sokka T, Lietsalmi AM, Kautiainen H, Hannonen P. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579596&dopt=Abstract
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Effects of needle-arthroscopic lavage with different volumes of fluid on knee synovitis in rheumatoid arthritis. Author(s): Tanaka N, Sakahashi H, Sato E, Hirose K, Ishii S. Source: Clinical Rheumatology. 2002 February; 21(1): 4-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954883&dopt=Abstract
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Effects of rheumatoid arthritis on sexual activity and relationships. Author(s): Hill J, Bird H, Thorpe R. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 280-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595623&dopt=Abstract
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Effects of treatment with etanercept (Enbrel, TNRF:Fc) on rheumatoid arthritis evaluated by Doppler ultrasonography. Author(s): Terslev L, Torp-Pedersen S, Qvistgaard E, Kristoffersen H, Rogind H, Danneskiold-Samsoe B, Bliddal H. Source: Annals of the Rheumatic Diseases. 2003 February; 62(2): 178-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525391&dopt=Abstract
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Effects of tumor necrosis factor-alpha inhibitors on lung lesions with rheumatoid arthritis. Author(s): Inoue K, Takano H, Yanagisawa R, Yoshikawa T. Source: Chest. 2003 July; 124(1): 413-4; Author Reply 414. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853558&dopt=Abstract
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Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Author(s): Choy EH, Hazleman B, Smith M, Moss K, Lisi L, Scott DG, Patel J, Sopwith M, Isenberg DA. Source: Rheumatology (Oxford, England). 2002 October; 41(10): 1133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364632&dopt=Abstract
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Efficiency of colchicine and corticosteroids in a leg ulceration with cholesterol embolism in a woman with rheumatoid arthritis. Author(s): Verneuil L, Ze Bekolo R, Dompmartin A, Comoz F, Marcelli C, Leroy D. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 1014-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869676&dopt=Abstract
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Elbow synovectomy on patients with juvenile rheumatoid arthritis. Author(s): Maenpaa H, Kuusela P, Lehtinen J, Savolainen A, Kautiainen H, Belt E. Source: Clinical Orthopaedics and Related Research. 2003 July; (412): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838054&dopt=Abstract
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Elevated levels of platelet microparticles are associated with disease activity in rheumatoid arthritis. Author(s): Knijff-Dutmer EA, Koerts J, Nieuwland R, Kalsbeek-Batenburg EM, van de Laar MA. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1498-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115179&dopt=Abstract
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Elevated levels of small, low-density lipoprotein with high affinity for arterial matrix components in patients with rheumatoid arthritis: possible contribution of phospholipase A2 to this atherogenic profile. Author(s): Hurt-Camejo E, Paredes S, Masana L, Camejo G, Sartipy P, Rosengren B, Pedreno J, Vallve JC, Benito P, Wiklund O. Source: Arthritis and Rheumatism. 2001 December; 44(12): 2761-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762936&dopt=Abstract
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Elevated levels of synovial fluid antibodies reactive with the small proteoglycans biglycan and decorin in patients with rheumatoid arthritis or other joint diseases. Author(s): Polgar A, Falus A, Koo E, Ujfalussy I, Sesztak M, Szuts I, Konrad K, Hodinka L, Bene E, Meszaros G, Ortutay Z, Farkas E, Paksy A, Buzas EI. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 522-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649398&dopt=Abstract
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Eligibility of patients in routine care for major clinical trials of anti-tumor necrosis factor alpha agents in rheumatoid arthritis. Author(s): Sokka T, Pincus T. Source: Arthritis and Rheumatism. 2003 February; 48(2): 313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571838&dopt=Abstract
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Elucidation of the relationship between synovitis and bone damage: a randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Author(s): Conaghan PG, O'Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon WW, Quinn M, Karim Z, Green MJ, Proudman S, Isaacs J, Emery P. Source: Arthritis and Rheumatism. 2003 January; 48(1): 64-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528105&dopt=Abstract
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Emergence of rheumatoid arthritis (RA) in the black peoples of Africa. Author(s): McGill P, Njobvu P. Source: Clinical Rheumatology. 2002 February; 21(1): 86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954895&dopt=Abstract
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Environmental risk factors for rheumatoid arthritis. Author(s): Khuder SA, Peshimam AZ, Agraharam S. Source: Rev Environ Health. 2002 October-December; 17(4): 307-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611472&dopt=Abstract
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Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Author(s): Symmons DP. Source: Best Practice & Research. Clinical Rheumatology. 2002 December; 16(5): 707-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473269&dopt=Abstract
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Epitope-specific recognition of type II collagen by rheumatoid arthritis antibodies is shared with recognition by antibodies that are arthritogenic in collagen-induced arthritis in the mouse. Author(s): Burkhardt H, Koller T, Engstrom A, Nandakumar KS, Turnay J, Kraetsch HG, Kalden JR, Holmdahl R. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2339-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355481&dopt=Abstract
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Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: accurate quantification using real-time polymerase chain reaction. Author(s): Balandraud N, Meynard JB, Auger I, Sovran H, Mugnier B, Reviron D, Roudier J, Roudier C. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746895&dopt=Abstract
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Erosion healing in rheumatoid arthritis after anakinra treatment. Author(s): Rau R, Sander O, Wassenberg S. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 671-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810433&dopt=Abstract
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Erythroblast iron metabolism and serum soluble transferrin receptor values in the anemia of rheumatoid arthritis. Author(s): Fitzsimons EJ, Houston T, Munro R, Sturrock RD, Speekenbrink AB, Brock JH. Source: Arthritis and Rheumatism. 2002 April 15; 47(2): 166-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954010&dopt=Abstract
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Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis. Author(s): Wong JB, Singh G, Kavanaugh A. Source: The American Journal of Medicine. 2002 October 1; 113(5): 400-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401535&dopt=Abstract
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Etanercept added to background methotrexate therapy in patients with rheumatoid arthritis: continued observations. Author(s): Kremer JM, Weinblatt ME, Bankhurst AD, Bulpitt KJ, Fleischmann RM, Jackson CG, Atkins KM, Feng A, Burge DJ. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1493-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794815&dopt=Abstract
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Etanercept treatment of rheumatoid arthritis in the “real world”. Author(s): Smith MD. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 95-6; Author Reply 96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480688&dopt=Abstract
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Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and juvenile rheumatoid arthritis. Author(s): Culy CR, Keating GM. Source: Drugs. 2002; 62(17): 2493-537. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421111&dopt=Abstract
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Etanercept-induced lupus-like syndrome in a patient with rheumatoid arthritis. Author(s): Carlson E, Rothfield N. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1165-6; Author Reply 1166. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687569&dopt=Abstract
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Ethnic variation in the clinical manifestations of rheumatoid arthritis: role of HLADRB1 alleles. Author(s): Del Rincon I, Battafarano DF, Arroyo RA, Murphy FT, Fischbach M, Escalante A. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687511&dopt=Abstract
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Evaluation of eutectic lidocaine/prilocaine cream (EMLA) for steroid joint injection in children with juvenile rheumatoid arthritis: a double blind, randomized, placebo controlled trial. Author(s): Uziel Y, Berkovitch M, Gazarian M, Koren G, Silverman ED, Schneider R, Laxer RM. Source: The Journal of Rheumatology. 2003 March; 30(3): 594-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610822&dopt=Abstract
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Evaluation of respiratory status and mandibular movement after total temporomandibular joint replacement in patients with rheumatoid arthritis. Author(s): Mishima K, Yamada T, Sugahara T. Source: International Journal of Oral and Maxillofacial Surgery. 2003 June; 32(3): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767874&dopt=Abstract
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Evidence for the benefit of aerobic and strengthening exercise in rheumatoid arthritis. Author(s): Stenstrom CH, Minor MA. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 428-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794800&dopt=Abstract
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Evidence from clinical trials and long-term observational studies that diseasemodifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review. Author(s): Pincus T, Ferraccioli G, Sokka T, Larsen A, Rau R, Kushner I, Wolfe F. Source: Rheumatology (Oxford, England). 2002 December; 41(12): 1346-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468813&dopt=Abstract
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Evidence of clonotypic pattern of T-cell repertoire in synovial fluid of children with juvenile rheumatoid arthritis at the onset of the disease. Author(s): Chini L, Bardare M, Cancrini C, Angelini F, Mancia L, Cortis E, Finocchi A, Riccardi C, Rossi P. Source: Scandinavian Journal of Immunology. 2002 November; 56(5): 512-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410801&dopt=Abstract
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Evidence supporting the benefit of early intervention in rheumatoid arthritis. Author(s): Emery P. Source: J Rheumatol Suppl. 2002 November; 66: 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435162&dopt=Abstract
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Evolving concepts of rheumatoid arthritis. Author(s): Firestein GS. Source: Nature. 2003 May 15; 423(6937): 356-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748655&dopt=Abstract
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Expanding role of biologic agents in rheumatoid arthritis. Author(s): Kalden JR. Source: J Rheumatol Suppl. 2002 November; 66: 27-37. Review. Erratum In: J Rheumatol Suppl. 2003 January; 301(1): 209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435166&dopt=Abstract
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Experiencing health in the context of rheumatoid arthritis. Author(s): Schmidt BJ, Brauer DJ, Peden-McAlpine C. Source: Nursing Science Quarterly. 2003 April; 16(2): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728834&dopt=Abstract
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Experimental validation of Monte Carlo depth-dose calculations using radiochromic dye film dosimetry for a beta-gamma 153Sm radionuclide applied to the treatment of rheumatoid arthritis. Author(s): Villareal-Barajas JE, Ferro-Flores G, Hernandez-Oviedo O. Source: Radiat Prot Dosimetry. 2002; 101(1-4): 439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382786&dopt=Abstract
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Expression analysis of the glucocorticoid receptor and the nuclear factor-kB subunit p50 in lymphocytes from patients with rheumatoid arthritis. Author(s): Eggert M, Kluter A, Rusch D, Schmidt KL, Dotzlaw H, Schulz M, Pabst W, Boke J, Renkawitz R, Neeck G. Source: The Journal of Rheumatology. 2002 December; 29(12): 2500-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465142&dopt=Abstract
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Expression and function of the co-stimulator H4/ICOS on activated T cells of patients with rheumatoid arthritis. Author(s): Okamoto T, Saito S, Yamanaka H, Tomatsu T, Kamatani N, Ogiuchi H, Uchiyama T, Yagi J. Source: The Journal of Rheumatology. 2003 June; 30(6): 1157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784384&dopt=Abstract
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Expression and regulation of Toll-like receptor 2 in rheumatoid arthritis synovium. Author(s): Seibl R, Birchler T, Loeliger S, Hossle JP, Gay RE, Saurenmann T, Michel BA, Seger RA, Gay S, Lauener RP. Source: American Journal of Pathology. 2003 April; 162(4): 1221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651614&dopt=Abstract
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Expression of activation-induced, T cell-derived, and chemokine-related cytokine/lymphotactin and its functional role in rheumatoid arthritis. Author(s): Blaschke S, Middel P, Dorner BG, Blaschke V, Hummel KM, Kroczek RA, Reich K, Benoehr P, Koziolek M, Muller GA. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1858-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847680&dopt=Abstract
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Expression of folylpolyglutamyl synthetase predicts poor response to methotrexate therapy in patients with rheumatoid arthritis. Author(s): Stranzl T, Wolf J, Leeb BF, Smolen JS, Pirker R, Filipits M. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673886&dopt=Abstract
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Expression of lactoferrin on neutrophil granulocytes from synovial fluid and peripheral blood of patients with rheumatoid arthritis. Author(s): Caccavo D, Garzia P, Sebastiani GD, Ferri GM, Galluzzo S, Vadacca M, Rigon A, Afeltra A, Amoroso A. Source: The Journal of Rheumatology. 2003 February; 30(2): 220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563671&dopt=Abstract
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Expression of melanoma antigen gene by cells from inflamed joints in juvenile rheumatoid arthritis. Author(s): McCurdy DK, Tai LQ, Imfeld KL, Schwartz M, Zaldivar F, Berman MA. Source: The Journal of Rheumatology. 2002 October; 29(10): 2219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375337&dopt=Abstract
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Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. Author(s): Frosch M, Vogl T, Seeliger S, Wulffraat N, Kuis W, Viemann D, Foell D, Sorg C, Sunderkotter C, Roth J. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2622-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130482&dopt=Abstract
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Expression of pleiotrophin, an embryonic growth and differentiation factor, in rheumatoid arthritis. Author(s): Pufe T, Bartscher M, Petersen W, Tillmann B, Mentlein R. Source: Arthritis and Rheumatism. 2003 March; 48(3): 660-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632418&dopt=Abstract
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Expression of the apoptosis accelerator Bax in rheumatoid arthritis synovium. Author(s): Hilbers I, Hansen T, Petrow PK, Gaumann A, Brauer R, Salzmann G, Gay RE, Kosmehl H, Kirkpatrick CJ, Gay S, Kriegsmann J. Source: Rheumatology International. 2003 March; 23(2): 75-81. Epub 2002 October 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634940&dopt=Abstract
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Expression of the dendritic cell-associated C-type lectin DC-SIGN by inflammatory matrix metalloproteinase-producing macrophages in rheumatoid arthritis synovium and interaction with intercellular adhesion molecule 3-positive T cells. Author(s): van Lent PL, Figdor CG, Barrera P, van Ginkel K, Sloetjes A, van den Berg WB, Torensma R. Source: Arthritis and Rheumatism. 2003 February; 48(2): 360-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571844&dopt=Abstract
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Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNK. Author(s): Sundarrajan M, Boyle DL, Chabaud-Riou M, Hammaker D, Firestein GS. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2450-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130464&dopt=Abstract
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Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Author(s): Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Source: Annals of the Rheumatic Diseases. 2003 August; 62(8): 722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860726&dopt=Abstract
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Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis. Author(s): Hoekstra M, van Ede AE, Haagsma CJ, van de Laar MA, Huizinga TW, Kruijsen MW, Laan RF. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695153&dopt=Abstract
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Factors influencing uptake of influenza vaccination in patients with rheumatoid arthritis. Author(s): Bridges MJ, Coady D, Kelly CA, Hamilton J, Heycock C. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 685. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810440&dopt=Abstract
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Factors related to radiological damage in 61 Spaniards with early rheumatoid arthritis. Author(s): Richi P, Balsa A, Munoz-Fernandez S, Villaverde V, Fernandez-Prada M, Vicario JL, Martin-Mola E. Source: Annals of the Rheumatic Diseases. 2002 March; 61(3): 270-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830438&dopt=Abstract
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Failure of hallux MP preservation surgery for rheumatoid arthritis. Author(s): Thordarson DB, Aval S, Krieger L. Source: Foot & Ankle International / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society. 2002 June; 23(6): 486-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095115&dopt=Abstract
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False positive elevation of cardiac troponin I in seropositive rheumatoid arthritis. Author(s): Katwa G, Komatireddy G, Walker SE. Source: The Journal of Rheumatology. 2001 December; 28(12): 2750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764229&dopt=Abstract
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False positive elevation of cardiac troponin I in seropositive rheumatoid arthritis. Author(s): Bas S, Genevay S, Mensi N. Source: The Journal of Rheumatology. 2002 December; 29(12): 2665. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465175&dopt=Abstract
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FC gamma RIIa polymorphism in patients with rheumatoid arthritis. Author(s): Pawlik A, Ostanek L, Brzosko I, Brzosko M, Fabrycy IF, Florczak M, Szklarz BG. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 841-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508778&dopt=Abstract
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Fcgamma receptor expression levels on monocytes are elevated in rheumatoid arthritis patients with high erythrocyte sedimentation rate who do not use antirheumatic drugs. Author(s): Wijngaarden S, van Roon JA, Bijlsma JW, van de Winkel JG, Lafeber FP. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 681-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709546&dopt=Abstract
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FcgammaRIIIA-158V and rheumatoid arthritis: a confirmation study. Author(s): Morgan AW, Keyte VH, Babbage SJ, Robinson JI, Ponchel F, Barrett JH, Bhakta BB, Bingham SJ, Buch MH, Conaghan PG, Gough A, Green M, Lawson CA, Pease CT, Markham AF, Ollier WE, Emery P, Worthington J, Isaacs JD. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 528-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649399&dopt=Abstract
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Female patients tend to alter their diet following the diagnosis of rheumatoid arthritis and breast cancer. Author(s): Salminen E, Heikkila S, Poussa T, Lagstrom H, Saario R, Salminen S. Source: Preventive Medicine. 2002 May; 34(5): 529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11969354&dopt=Abstract
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Female sex increases risk for rheumatoid arthritis only in individuals encoding lowrisk HLA-DRB1 alleles. Author(s): de Vries N, Tak PP, Tijssen H, van Riel PL, van de Putte LB. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1762-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794845&dopt=Abstract
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Fibroblast-like synoviocytes from rheumatoid arthritis patients express functional IL15 receptor complex: endogenous IL-15 in autocrine fashion enhances cell proliferation and expression of Bcl-x(L) and Bcl-2. Author(s): Kurowska M, Rudnicka W, Kontny E, Janicka I, Chorazy M, Kowalczewski J, Ziolkowska M, Ferrari-Lacraz S, Strom TB, Maslinski W. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 August 15; 169(4): 1760-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165497&dopt=Abstract
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Fibroblast-like synoviocytes from rheumatoid arthritis patients express less FLICEinhibitory protein than fibroblast-like synoviocytes from trauma patients: comment on the article by Schedel et al. Author(s): Tolboom TC, Medema JP, van Gaalen FA, Pieterman E, Huizinga TW, Toes RE. Source: Arthritis and Rheumatism. 2003 March; 48(3): 858-9; Author Reply 859. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632447&dopt=Abstract
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Fibromyalgia in patients with rheumatoid arthritis is associated with higher scores of disability. Author(s): Naranjo A, Ojeda S, Francisco F, Erausquin C, Rua-Figueroa I, RodriguezLozano C. Source: Annals of the Rheumatic Diseases. 2002 July; 61(7): 660-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079919&dopt=Abstract
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Fifty years of experience with cortisone therapy in the study and treatment of rheumatoid arthritis. Author(s): Neeck G. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 28-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114256&dopt=Abstract
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Fine needle aspiration cytology of gouty tophus in a patient with rheumatoid arthritis. Author(s): Paik SS, Park MH. Source: Acta Cytol. 2002 September-October; 46(5): 1024-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365206&dopt=Abstract
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First do no harm--a bone of contention in rheumatoid arthritis. Author(s): Zochling J, March L. Source: The Journal of Rheumatology. 2002 September; 29(9): 1818-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233872&dopt=Abstract
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Five-year followup of rheumatoid arthritis patients after early treatment with diseasemodifying antirheumatic drugs versus treatment according to the pyramid approach in the first year. Author(s): Verstappen SM, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, Borg EJ, Hofman DM, van der Veen MJ; Utrecht Arthritis Cohort Study Group. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1797-807. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847672&dopt=Abstract
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FLICE-inhibitory protein expression in synovial fibroblasts and at sites of cartilage and bone erosion in rheumatoid arthritis. Author(s): Schedel J, Gay RE, Kuenzler P, Seemayer C, Simmen B, Michel BA, Gay S. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1512-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115181&dopt=Abstract
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Focusing interventions for disability among patients with rheumatoid arthritis. Author(s): Yelin EH, Katz PP. Source: Arthritis and Rheumatism. 2002 June 15; 47(3): 231-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115150&dopt=Abstract
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Follow up studies in rheumatoid arthritis. Author(s): Landewe R, van der Heijde D. Source: Annals of the Rheumatic Diseases. 2002 June; 61(6): 479-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006315&dopt=Abstract
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Forearm bone mineral density in patients with rheumatoid arthritis. Author(s): Iwamoto J, Takeda T, Ichimura S. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2002; 7(5): 528-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355125&dopt=Abstract
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Forearm bone mineral density in postmenopausal women with rheumatoid arthritis. Author(s): Iwamoto J, Takeda T, Ichimura S. Source: Calcified Tissue International. 2002 January; 70(1): 1-8. Epub 2001 December 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907701&dopt=Abstract
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Frequency of abnormal hand and wrist radiographs at time of diagnosis of polyarticular juvenile rheumatoid arthritis. Author(s): Mason T, Reed AM, Nelson AM, Thomas KB, Patton A, Hoffman AD, Achenbach S, O'Fallon WM. Source: The Journal of Rheumatology. 2002 October; 29(10): 2214-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375336&dopt=Abstract
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Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Author(s): Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2287-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355475&dopt=Abstract
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Fucosylation of alpha1-acid glycoprotein (orosomucoid) compared with traditional biochemical markers of inflammation in recent onset rheumatoid arthritis. Author(s): Ryden I, Pahlsson P, Lundblad A, Skogh T. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 March; 317(1-2): 221-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814479&dopt=Abstract
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Functional activity of mononuclear phagocytes in rheumatoid arthritis. Author(s): Arleevskaya MI, Khaliullina DG, Tsibulkin AP. Source: Russ J Immunol. 2002 April; 7(1): 69-72. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687270&dopt=Abstract
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Functional analysis of discoidin domain receptor 2 in synovial fibroblasts in rheumatoid arthritis. Author(s): Wang J, Lu H, Liu X, Deng Y, Sun T, Li F, Ji S, Nie X, Yao L. Source: Journal of Autoimmunity. 2002 November; 19(3): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419287&dopt=Abstract
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Functional and health status assessment in patients with rheumatoid arthritis. Author(s): Stamm TA, Machold KP, Smolen JS. Source: Acta Medica Austriaca. 2002; 29(1): 30-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899751&dopt=Abstract
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Functional characterization of adherent synovial fluid cells in rheumatoid arthritis: destructive potential in vitro and in vivo. Author(s): Neidhart M, Seemayer CA, Hummel KM, Michel BA, Gay RE, Gay S. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1873-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847681&dopt=Abstract
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Functional disability in relation to radiological damage and disease activity in patients with rheumatoid arthritis in remission. Author(s): Molenaar ET, Voskuyl AE, Dijkmans BA. Source: The Journal of Rheumatology. 2002 February; 29(2): 267-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842821&dopt=Abstract
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Functional disability in rheumatoid arthritis patients compared with a community population in Finland. Author(s): Sokka T, Krishnan E, Hakkinen A, Hannonen P. Source: Arthritis and Rheumatism. 2003 January; 48(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528104&dopt=Abstract
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Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Author(s): Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K. Source: Nature Genetics. 2003 August; 34(4): 395-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833157&dopt=Abstract
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Functional performance in rheumatoid arthritis. Author(s): Oliver S. Source: Prof Nurse. 2000 October; 16(1): 827-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029718&dopt=Abstract
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gamma delta-Lymphocytes in the peripheral blood of patients with rheumatoid arthritis--correlation with clinical and laboratory parameters of the disease and with the treatment used. Author(s): Kowal-Bielecka O, Mroz R, Bernacka K, Kowal E, Sierakowski S. Source: Rocz Akad Med Bialymst. 2001; 46: 170-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780560&dopt=Abstract
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Gene therapy for rheumatoid arthritis. Author(s): Gouze JN, Ghivizzani SC, Gouze E, Palmer GD, Betz OB, Robbins PD, Evans CH, Herndon JH. Source: Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2001 December; 6(2): 211-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901469&dopt=Abstract
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Gene therapy for rheumatoid arthritis. Author(s): Bessis N, Doucet C, Cottard V, Douar AM, Firat H, Jorgensen C, Mezzina M, Boissier MC. Source: The Journal of Gene Medicine. 2002 November-December; 4(6): 581-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439850&dopt=Abstract
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Gene therapy for rheumatoid arthritis. Lessons from animal models, including studies on interleukin-4, interleukin-10, and interleukin-1 receptor antagonist as potential disease modulators. Author(s): van de Loo FA, van den Berg WB. Source: Rheumatic Diseases Clinics of North America. 2002 February; 28(1): 127-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840694&dopt=Abstract
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Gene transfer of protective cytokines in rheumatoid arthritis. Author(s): Distler O, Seemayer CA, Pap T, Gay RE, Neidhart M, Muller-Ladner U, Gay S. Source: Advances in Experimental Medicine and Biology. 2001; 495: 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11774572&dopt=Abstract
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Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease loci. Author(s): Griffiths MM, Remmers EF. Source: Immunological Reviews. 2001 December; 184: 172-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086311&dopt=Abstract
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Genetic approaches to the investigation of rheumatoid arthritis. Author(s): Barton A, Ollier W. Source: Current Opinion in Rheumatology. 2002 May; 14(3): 260-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981324&dopt=Abstract
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Genetic determinants of rheumatoid arthritis: the inducible nitric oxide synthase (NOS2) gene promoter polymorphism. Author(s): Pascual M, Lopez-Nevot MA, Caliz R, Koeleman BP, Balsa A, PascualSalcedo D, Martin J. Source: Genes and Immunity. 2002 August; 3(5): 299-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140750&dopt=Abstract
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Genetic drift as an explanation for the reduced incidence of rheumatoid arthritis. Author(s): Huizinga TW, Linn-Rasker S, Lard LR, Westendorp RG. Source: Arthritis and Rheumatism. 2002 November; 46(11): 3107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428264&dopt=Abstract
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Genetic epidemiology of rheumatoid arthritis. Author(s): Harney S, Wordsworth BP. Source: Tissue Antigens. 2002 December; 60(6): 465-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542739&dopt=Abstract
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Genetic influences on rheumatoid arthritis in African Americans. Author(s): Hughes LB, Moreland LW, Bridges SL Jr. Source: Immunologic Research. 2002; 26(1-3): 15-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403341&dopt=Abstract
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Genetic markers for the efficacy of tumour necrosis factor blocking therapy in rheumatoid arthritis. Author(s): Padyukov L, Lampa J, Heimburger M, Ernestam S, Cederholm T, Lundkvist I, Andersson P, Hermansson Y, Harju A, Klareskog L, Bratt J. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 526-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759288&dopt=Abstract
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Genetic studies in rheumatoid arthritis. Author(s): Grennan DM, Sanders PA. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 490-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626806&dopt=Abstract
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Genetic studies, clinical heterogeneity, and disease outcome studies in rheumatoid arthritis. Author(s): Moxley G, Cohen HJ. Source: Rheumatic Diseases Clinics of North America. 2002 February; 28(1): 39-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840697&dopt=Abstract
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Genetics in rheumatoid arthritis. Author(s): Huizinga TW. Source: Curr Rheumatol Rep. 2002 June; 4(3): 195-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010603&dopt=Abstract
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Genetics of rheumatoid arthritis: is there a scientific explanation for the human leukocyte antigen association? Author(s): Buckner JH, Nepom GT. Source: Current Opinion in Rheumatology. 2002 May; 14(3): 254-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981323&dopt=Abstract
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Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients. Author(s): Ramos-Remus C, Dorazco-Barragan G, Aceves-Avila FJ, Alcaraz-Lopez F, Fuentes-Ramirez F, Michel-Diaz J, Torres-Bugarin O, Ventura-Aguilar A, ZunigaGonzalez G. Source: Clin Exp Rheumatol. 2002 March-April; 20(2): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051400&dopt=Abstract
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Getting to the heart of the matter in systemic lupus and rheumatoid arthritis. Author(s): Manzi S, Wasko MC. Source: Bulletin on the Rheumatic Diseases. 2001; 50(5): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387096&dopt=Abstract
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Giant intraosseous cyst-like lesions in rheumatoid arthritis report of a case. Author(s): Lohse A, Carbillet JP, Onimus M, Stevenel F, Toussirot E, Wendling D. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2003 February; 70(1): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639622&dopt=Abstract
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Global functional status in rheumatoid arthritis: disease duration and patient age. Author(s): Fonseca JE, Canhao H, Teixeira da CJ, Pereira da SJ, Queiroz MV. Source: Clinical Rheumatology. 2002 February; 21(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954881&dopt=Abstract
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Glucocorticoid receptor downregulation in early diagnosed rheumatoid arthritis. Author(s): Huisman AM, Van Everdingen AA, Wenting MJ, Siewertsz Van Reesema DR, Lafeber FP, Jacobs JW, Bijlsma JW. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 64-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114259&dopt=Abstract
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Glucocorticoid receptor up-regulation in early rheumatoid arthritis treated with low dose prednisone or placebo. Author(s): Huisman AM, Siewertsz van Everdingen AA, Wenting MJ, Lafeber F, van Reesema DR, Jacobs JW, Bijlsma JW. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 217-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747278&dopt=Abstract
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Glucocorticoid use in rheumatoid arthritis. Author(s): Saag KG. Source: Curr Rheumatol Rep. 2002 June; 4(3): 218-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010606&dopt=Abstract
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Glucocorticoids and rheumatoid arthritis: back to the future? Author(s): Moreland LW, O'Dell JR. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2553-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384910&dopt=Abstract
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Glucocorticoids in rheumatoid arthritis: effects on erosions and bone. Author(s): Bijlsma JW, Van Everdingen AA, Huisman M, De Nijs RN, Jacobs JW. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 82-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114262&dopt=Abstract
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Glucose-6-phosphate isomerase is not a specific autoantigen in rheumatoid arthritis. Author(s): Herve CA, Wait R, Venables PJ. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 986-8. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730513&dopt=Abstract
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Gluten and the small intestine in rheumatoid arthritis. Author(s): Binder HJ, O'Brien WM, Spiro HM, Hollingsworth JW. Source: Jama : the Journal of the American Medical Association. 1966 March 7; 195(10): 857-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608175&dopt=Abstract
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Glycopeptide specificity of helper T cells obtained in mouse models for rheumatoid arthritis. Author(s): Holm B, Backlund J, Recio MA, Holmdahl R, Kihlberg J. Source: Chembiochem : a European Journal of Chemical Biology. 2002 December 2; 3(12): 1209-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465029&dopt=Abstract
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Glycosaminoglycans are a potential cause of rheumatoid arthritis. Author(s): Wang JY, Roehrl MH. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 29; 99(22): 14362-7. Epub 2002 Oct 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391302&dopt=Abstract
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Guidelines for the management of rheumatoid arthritis: 2002 Update. Author(s): American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Source: Arthritis and Rheumatism. 2002 February; 46(2): 328-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840435&dopt=Abstract
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Guidelines for the management of rheumatoid arthritis: 2002 update. Author(s): Newsome G; American College of Rheumatology. Source: Journal of the American Academy of Nurse Practitioners. 2002 October; 14(10): 432-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426799&dopt=Abstract
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Haemophagocytic syndrome in a rheumatoid arthritis patient treated with infliximab. Author(s): Aouba A, De Bandt M, Aslangul E, Atkhen N, Patri B. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 800-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771439&dopt=Abstract
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Haemorrhagic colitis due to Escherichia coli O103:H2 associated with infliximab therapy in a patient with rheumatoid arthritis. Author(s): Kirchgatterer A, Weber T, Hinterreiter M, Knoflach P, Allerberger F. Source: Rheumatology (Oxford, England). 2002 March; 41(3): 355-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934982&dopt=Abstract
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Hand bone densitometry in rheumatoid arthritis, a five year longitudinal study: an outcome measure and a prognostic marker. Author(s): Deodhar AA, Brabyn J, Pande I, Scott DL, Woolf AD. Source: Annals of the Rheumatic Diseases. 2003 August; 62(8): 767-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860734&dopt=Abstract
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Health related quality of life in women with elderly onset rheumatoid arthritis. Author(s): Mikuls T, Saag K, Criswell L, Merlino L, Cerhan JR. Source: The Journal of Rheumatology. 2003 May; 30(5): 952-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734888&dopt=Abstract
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Health status of patients with juvenile rheumatoid arthritis at 1 and 5 years after diagnosis. Author(s): Bowyer SL, Roettcher PA, Higgins GC, Adams B, Myers LK, Wallace C, Rennebohm R, Moore TL, Pepmueller PH, Spencer C, Wagner-Weiner L, Rabinovich E, Passo M, Lovell DJ, McCurdy D, Zemel L, Schikler KN, Szer I, Kurtin P, Lindsley C. Source: The Journal of Rheumatology. 2003 February; 30(2): 394-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563701&dopt=Abstract
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Health-related quality of life in early rheumatoid arthritis: impact of disease and treatment response. Author(s): Kosinski M, Kujawski SC, Martin R, Wanke LA, Buatti MC, Ware JE Jr, Perfetto EM. Source: Am J Manag Care. 2002 March; 8(3): 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915973&dopt=Abstract
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Health-related quality of life measurements and studies in rheumatoid arthritis. Author(s): Lubeck DP. Source: Am J Manag Care. 2002 September; 8(9): 811-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234022&dopt=Abstract
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Hearing loss and middle ear involvement in rheumatoid arthritis. Author(s): Ozcan M, Karakus MF, Gunduz OH, Tuncel U, Sahin H. Source: Rheumatology International. 2002 May; 22(1): 16-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120906&dopt=Abstract
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Hearing loss in rheumatoid arthritis. Author(s): Raut VV, Cullen J, Cathers G. Source: The Journal of Otolaryngology. 2001 October; 30(5): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771022&dopt=Abstract
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Helicobacter pylori infection in rheumatoid arthritis: effect of drugs on prevalence and correlation with gastroduodenal lesions. Author(s): Kelly C, Saravanan V. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 388; Author Reply 388. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595646&dopt=Abstract
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Helicobacter pylori infection in rheumatoid arthritis: effect of drugs on prevalence and correlation with gastroduodenal lesions. Author(s): Ishikawa N, Fuchigami T, Matsumoto T, Kobayashi H, Sakai Y, Tabata H, Takubo N, Yamamoto S, Nakanishi M, Tomioka K, Fujishima M. Source: Rheumatology (Oxford, England). 2002 January; 41(1): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792883&dopt=Abstract
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Hematological manifestations of rheumatoid arthritis. Author(s): Bowman SJ. Source: Scandinavian Journal of Rheumatology. 2002; 31(5): 251-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455813&dopt=Abstract
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Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthritis treated with infliximab and low dose methotrexate. Author(s): Ostuni P, Botsios C, Punzi L, Sfriso P, Todesco S. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 686-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810441&dopt=Abstract
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Heterogeneity between men and women in the influence of the HLA-DRB1 shared epitope on the clinical expression of rheumatoid arthritis. Author(s): del Rincon I, Battafarano DF, Arroyo RA, Murphy FT, Escalante A. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1480-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115177&dopt=Abstract
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Heterogeneous requirement of IkappaB kinase 2 for inflammatory cytokine and matrix metalloproteinase production in rheumatoid arthritis: implications for therapy. Author(s): Andreakos E, Smith C, Kiriakidis S, Monaco C, de Martin R, Brennan FM, Paleolog E, Feldmann M, Foxwell BM. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1901-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847684&dopt=Abstract
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Hidden hazards and practical problems: comment on the 2002 update of the American College of Rheumatology Guidelines for the Management of Rheumatoid Arthritis. Author(s): Block SR. Source: Arthritis and Rheumatism. 2002 November; 46(11): 3102-3; Author Reply 3103-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428258&dopt=Abstract
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High dose chemotherapy and autologous hematopoietic stem cell transplantation for rheumatoid arthritis: a review. Author(s): Verburg RJ, Toes RE, Fibbe WE, Breedveld FC, van Laar JM. Source: Human Immunology. 2002 August; 63(8): 627-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121670&dopt=Abstract
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High dose chemotherapy and hematopoietic stem cell transplantation: a study of treatment preference in patients with rheumatoid arthritis and rheumatologists. Author(s): Verburg RJ, Mahabali SD, Stiggelbout AM, Sont JK, van Laar JM. Source: The Journal of Rheumatology. 2002 August; 29(8): 1653-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180724&dopt=Abstract
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High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Author(s): del Rincon ID, Williams K, Stern MP, Freeman GL, Escalante A. Source: Arthritis and Rheumatism. 2001 December; 44(12): 2737-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762933&dopt=Abstract
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High levels of interleukin 13 in rheumatoid arthritis sera are modulated by tumor necrosis factor antagonist therapy: association with dendritic cell growth activity. Author(s): Tokayer A, Carsons SE, Chokshi B, Santiago-Schwarz F. Source: The Journal of Rheumatology. 2002 March; 29(3): 454-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908556&dopt=Abstract
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High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after antitumor necrosis factor alpha treatment. Author(s): Ziolkowska M, Kurowska M, Radzikowska A, Luszczykiewicz G, Wiland P, Dziewczopolski W, Filipowicz-Sosnowska A, Pazdur J, Szechinski J, Kowalczewski J, Rell-Bakalarska M, Maslinski W. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1744-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124857&dopt=Abstract
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High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Author(s): Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M, Inoue K, Yamada S, Ijiri K, Matsunaga S, Nakajima T, Komiya S, Maruyama I. Source: Arthritis and Rheumatism. 2003 April; 48(4): 971-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687539&dopt=Abstract
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High prevalence of thyroid autoantibodies in newly diagnosed rheumatoid arthritis patients. Author(s): Del Puente A, Savastano S, Nuzzo V, Esposito A, Lupoli G. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 137. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673907&dopt=Abstract
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High resolution ultrasound detects a decrease in pannus vascularisation of small finger joints in patients with rheumatoid arthritis receiving treatment with soluble tumour necrosis factor alpha receptor (etanercept). Author(s): Hau M, Kneitz C, Tony HP, Keberle M, Jahns R, Jenett M. Source: Annals of the Rheumatic Diseases. 2002 January; 61(1): 55-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779760&dopt=Abstract
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High response rate in the phase I/II study of meloxicam in juvenile rheumatoid arthritis. Author(s): Foeldvari I, Burgos-Vargas R, Thon A, Tuerck D. Source: The Journal of Rheumatology. 2002 May; 29(5): 1079-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022326&dopt=Abstract
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High-dose cyclophosphamide with stem cell rescue for severe rheumatoid arthritis: short-term efficacy correlates with reduction of macroscopic and histologic synovitis. Author(s): Bingham S, Veale D, Fearon U, Isaacs JD, Morgan G, Emery P, McGonagle D, Reece R, Clague R, Snowden JA. Source: Arthritis and Rheumatism. 2002 March; 46(3): 837-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920422&dopt=Abstract
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High-resolution ultrasound for the study of target joints in rheumatoid arthritis. Author(s): Alarcon GS, Lopez-Ben R, Moreland LW. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1969-70; Author Reply 1970-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124884&dopt=Abstract
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Hip disease in juvenile rheumatoid arthritis. Author(s): Spencer CH, Bernstein BH. Source: Current Opinion in Rheumatology. 2002 September; 14(5): 536-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192251&dopt=Abstract
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Histology of the craniocervical junction in chronic rheumatoid arthritis: a clinicopathologic analysis of 33 operative cases. Author(s): O'Brien MF, Casey AT, Crockard A, Pringle J, Stevens JM. Source: Spine. 2002 October 15; 27(20): 2245-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394902&dopt=Abstract
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HLA and cytokine gene polymorphisms in relation to occurrence of palindromic rheumatism and its progression to rheumatoid arthritis. Author(s): Maksymowych WP, Suarez-Almazor ME, Buenviaje H, Cooper BL, Degeus C, Thompson M, Russell AS. Source: The Journal of Rheumatology. 2002 November; 29(11): 2319-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415587&dopt=Abstract
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HLA DMA and DMB show no association with rheumatoid arthritis in US Caucasians. Author(s): Moxley G, Han J. Source: European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics. 2001 October; 28(5): 539-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881821&dopt=Abstract
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HLA haplotypes and susceptibility to rheumatoid arthritis. More than class II genes. Author(s): Pascual M, Mataran L, Jones G, Shing D, van der Slik AR, Giphart MJ, Schreuder GM, de Vries RR, Breedveld FC, Roovers E, Zanelli E, Martin J. Source: Scandinavian Journal of Rheumatology. 2002; 31(5): 275-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455817&dopt=Abstract
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HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjogren's syndrome. Author(s): Hadj Kacem H, Kaddour N, Adyel FZ, Bahloul Z, Ayadi H. Source: Rheumatology (Oxford, England). 2001 December; 40(12): 1370-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752507&dopt=Abstract
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HLA-DR/DQ haplotype in rheumatoid arthritis: novel allelic associations in UK Caucasians. Author(s): Milicic A, Lee D, Brown MA, Darke C, Wordsworth BP. Source: The Journal of Rheumatology. 2002 September; 29(9): 1821-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233873&dopt=Abstract
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HLA-DRB1 genes and susceptibility to rheumatoid arthritis in three ethnic groups from Malaysia. Author(s): Kong KF, Yeap SS, Chow SK, Phipps ME. Source: Autoimmunity. 2002 July; 35(4): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482190&dopt=Abstract
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HLA-DRB1 genotype associations in 793 white patients from a rheumatoid arthritis inception cohort: frequency, severity, and treatment bias. Author(s): Fries JF, Wolfe F, Apple R, Erlich H, Bugawan T, Holmes T, Bruce B. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2320-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355479&dopt=Abstract
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HLA-DRB1 status affects endothelial function in treated patients with rheumatoid arthritis. Author(s): Gonzalez-Juanatey C, Testa A, Garcia-Castelo A, Garcia-Porrua C, Llorca J, Vidan J, Hajeer AH, Ollier WE, Mattey DL, Gonzalez-Gay MA. Source: The American Journal of Medicine. 2003 June 1; 114(8): 647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798452&dopt=Abstract
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Hodgkin's disease following methotrexate therapy for rheumatoid arthritis. Author(s): Jardine DL, Colls BM. Source: N Z Med J. 2002 June 21; 115(1156): 293-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199007&dopt=Abstract
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Homing chemokines in rheumatoid arthritis. Author(s): Loetscher P, Moser B. Source: Arthritis Research. 2002; 4(4): 233-6. Epub 2002 January 31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106492&dopt=Abstract
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Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Author(s): van Ede AE, Laan RF, Blom HJ, Boers GH, Haagsma CJ, Thomas CM, De Boo TM, van de Putte LB. Source: Rheumatology (Oxford, England). 2002 June; 41(6): 658-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048292&dopt=Abstract
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Hormone mediation of immune responses in the progression of diabetes, rheumatoid arthritis and periodontal diseases. Author(s): Soory M. Source: Current Drug Targets. Immune, Endocrine and Metabolic Disorders. 2002 April; 2(1): 13-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477294&dopt=Abstract
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Hormones, pregnancy, and rheumatoid arthritis. Author(s): Olsen NJ, Kovacs WJ. Source: J Gend Specif Med. 2002 July-August; 5(4): 28-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192884&dopt=Abstract
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How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Author(s): Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. Source: Arthritis and Rheumatism. 2002 February; 46(2): 357-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840437&dopt=Abstract
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How to report radiographic data in randomized clinical trials in rheumatoid arthritis: guidelines from a roundtable discussion. Author(s): van der Heijde D, Simon L, Smolen J, Strand V, Sharp J, Boers M, Breedveld F, Weisman M, Weinblatt M, Rau R, Lipsky P. Source: Arthritis and Rheumatism. 2002 April 15; 47(2): 215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954017&dopt=Abstract
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Human IgG Fc-binding phage antibodies constructed from synovial fluid CD38+ B cells of patients with rheumatoid arthritis show the imprints of an antigen-dependent process of somatic hypermutation and clonal selection. Author(s): Van Esch WJ, Reparon-Schuijt CC, Hamstra HJ, Van Kooten C, Logtenberg T, Breedveld FC, Verweij CL. Source: Clinical and Experimental Immunology. 2003 February; 131(2): 364-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562401&dopt=Abstract
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Humanized mice as a model for rheumatoid arthritis. Author(s): Eming R, Visconti K, Hall F, Sekine C, Kobayashi K, Chen Q, Cope A, Kanazawa S, Peterlin M, Rijnders A, Boots A, Meijerink J, Sonderstrup G. Source: Arthritis Research. 2002; 4 Suppl 3: S133-40. Epub 2002 May 09. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110132&dopt=Abstract
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Hydroxychloroquine concentration-response relationships in patients with rheumatoid arthritis. Author(s): Munster T, Gibbs JP, Shen D, Baethge BA, Botstein GR, Caldwell J, Dietz F, Ettlinger R, Golden HE, Lindsley H, McLaughlin GE, Moreland LW, Roberts WN, Rooney TW, Rothschild B, Sack M, Sebba AI, Weisman M, Welch KE, Yocum D, Furst DE. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1460-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115175&dopt=Abstract
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Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue in patients with rheumatoid arthritis compared with osteoarthritis. Author(s): Kaufmann J, Mueller A, Voigt A, Carl HD, Gursche A, Zacher J, Stein G, Hein G. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 314-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595629&dopt=Abstract
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Hyperviscosity syndrome in rheumatoid arthritis with Felty's syndrome: case report and review of the literature. Author(s): Zakzook SI, Yunus MB, Mulconrey DS. Source: Clinical Rheumatology. 2002 February; 21(1): 82-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954894&dopt=Abstract
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Hypoglossal nerve palsy from cervical spine involvement in rheumatoid arthritis: 3 case reports. Author(s): Blankenship LD, Basford JR, Strommen JA, Andersen RJ. Source: Archives of Physical Medicine and Rehabilitation. 2002 February; 83(2): 269-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833033&dopt=Abstract
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Hypothalamic-pituitary-adrenal axis impairment in the pathogenesis of rheumatoid arthritis and polymyalgia rheumatica. Author(s): Cutolo M, Foppiani L, Minuto F. Source: J Endocrinol Invest. 2002; 25(10 Suppl): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508908&dopt=Abstract
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Hypothalamic-pituitary-adrenocortical and gonadal functions in rheumatoid arthritis. Author(s): Cutolo M, Sulli A, Pizzorni C, Craviotto C, Straub RH. Source: Annals of the New York Academy of Sciences. 2003 May; 992: 107-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794051&dopt=Abstract
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Hypothalamo-pituitary-adrenal axis dysregulation in patients with rheumatoid arthritis after the dexamethasone/corticotrophin releasing factor test. Author(s): Harbuz MS, Korendowych E, Jessop DS, Crown AL, Li pdfan SL, Kirwan JR. Source: The Journal of Endocrinology. 2003 July; 178(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844336&dopt=Abstract
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Identification of citrullinated rheumatoid arthritis-specific epitopes in natural filaggrin relevant for antifilaggrin autoantibody detection by line immunoassay. Author(s): Union A, Meheus L, Humbel RL, Conrad K, Steiner G, Moereels H, Pottel H, Serre G, De Keyser F. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1185-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115222&dopt=Abstract
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Identification of I kappa BL as the second major histocompatibility complex-linked susceptibility locus for rheumatoid arthritis. Author(s): Okamoto K, Makino S, Yoshikawa Y, Takaki A, Nagatsuka Y, Ota M, Tamiya G, Kimura A, Bahram S, Inoko H. Source: American Journal of Human Genetics. 2003 February; 72(2): 303-12. Epub 2002 December 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509789&dopt=Abstract
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Identification of radiologic healing phenomena in patients with rheumatoid arthritis. Author(s): Rau R, Wassenberg S, Herborn G, Perschel WT, Freitag G. Source: The Journal of Rheumatology. 2001 December; 28(12): 2608-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764205&dopt=Abstract
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Identification of radiologic healing phenomena in patients with rheumatoid arthritis. Author(s): Sharp JT. Source: The Journal of Rheumatology. 2002 October; 29(10): 2239; Author Reply 2239. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375342&dopt=Abstract
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Identification of self-epitopes recognized by T cells in rheumatoid arthritis demonstrates matrix metalloproteinases as a novel T cell target. Author(s): ter Steege J, Vianen M, van Bilsen J, Bijlsma J, Lafeber F, Wauben M. Source: The Journal of Rheumatology. 2003 June; 30(6): 1147-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784383&dopt=Abstract
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Imaging apoptosis in rheumatoid arthritis. Author(s): Vannier MW. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 October; 43(10): 1366-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368375&dopt=Abstract
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Imaging in rheumatoid arthritis--why MRI and ultrasonography can no longer be ignored. Author(s): Ostergaard M, Szkudlarek M. Source: Scandinavian Journal of Rheumatology. 2003; 32(2): 63-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737323&dopt=Abstract
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Immune complexes contain immunoglobulin A rheumatoid factor in serum and synovial fluid of patients with polyarticular juvenile rheumatoid arthritis. Author(s): Agarwal V, Misra R, Aggarwal A. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961181&dopt=Abstract
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Immunoglobulin E-rheumatoid factor in juvenile rheumatoid arthritis. Author(s): Ferreira RA, Ferriani VP, Sopelete MC, Silva DA, Mineo JR, Kiss MH, Silva CH. Source: Revista Do Hospital Das Clinicas. 2002 September-October; 57(5): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436177&dopt=Abstract
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Impact of socioeconomic status on the course of rheumatoid arthritis and on related use of health care services. Author(s): Jacobi CE, Mol GD, Boshuizen HC, Rupp I, Dinant HJ, Van Den Bos GA. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 567-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910565&dopt=Abstract
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Impaired autologous mixed lymphocyte reaction (AMLR) reactivity of peripheral blood T cell subsets in rheumatoid arthritis. Author(s): Keystone EC, Poplonski L, Snow KM, Martell M. Source: Clinical and Experimental Immunology. 1989 November; 78(2): 184-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412746&dopt=Abstract
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Impaired generation of taurine chloramine by synovial fluid neutrophils of rheumatoid arthritis patients. Author(s): Kontny E, Wojtecka-LUkasik E, Rell-Bakalarska K, Dziewczopolski W, Maslinski W, Maslinski S. Source: Amino Acids. 2002; 23(4): 415-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12436209&dopt=Abstract
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Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis. Author(s): Bazzichi L, Ciompi ML, Betti L, Rossi A, Melchiorre D, Fiorini M, Giannaccini G, Lucacchini A. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 761-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508766&dopt=Abstract
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Impaired responsiveness to NO in newly diagnosed patients with rheumatoid arthritis. Author(s): Bergholm R, Leirisalo-Repo M, Vehkavaara S, Makimattila S, Taskinen MR, Yki-Jarvinen H. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 October 1; 22(10): 163741. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377742&dopt=Abstract
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In vitro autoreactivity against skin and synovial cells in patients with juvenile idiopathic and rheumatoid arthritis. Author(s): Stechova K, Vavrincova P, Chudoba D, Frantlova M, Reitzova H, Sosna A, Zimak J, Lednicky L, Dickinson AM, Hromadnikova I. Source: Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology. 2002-2003; 70(2): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476032&dopt=Abstract
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Incidence of gastroduodenal ulcers in patients with rheumatoid arthritis after 12 weeks of rofecoxib, naproxen, or placebo: a multicentre, randomised, double blind study. Author(s): Hawkey CJ, Laine L, Simon T, Quan H, Shingo S, Evans J; Rofecoxib Rheumatoid Arthritis Endoscopy Study Group. Source: Gut. 2003 June; 52(6): 820-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740337&dopt=Abstract
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Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. Author(s): Wolfe F, Freundlich B, Straus WL. Source: The Journal of Rheumatology. 2003 January; 30(1): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508387&dopt=Abstract
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Increased endothelial expression of HLA-DQ and interleukin 1alpha in extra-articular rheumatoid arthritis. Results from immunohistochemical studies of skeletal muscle. Author(s): Turesson C, Englund P, Jacobsson LT, Sturfelt G, Truedsson L, Nennesmo I, Lundberg IE. Source: Rheumatology (Oxford, England). 2001 December; 40(12): 1346-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752503&dopt=Abstract
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Increased expression of Fcgamma receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor alpha and matrix metalloproteinase. Author(s): Blom AB, Radstake TR, Holthuysen AE, Sloetjes AW, Pesman GJ, Sweep FG, van de Loo FA, Joosten LA, Barrera P, van Lent PL, van den Berg WB. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1002-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687542&dopt=Abstract
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Increased inflammatory activity parallels increased basal nitric oxide production and blunted response to nitric oxide in vivo in rheumatoid arthritis. Author(s): Yki-Jarvinen H, Bergholm R, Leirisalo-Repo M. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 630-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810424&dopt=Abstract
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Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. Author(s): Jonsson SW, Backman C, Johnson O, Karp K, Lundstrom E, Sundqvist KG, Dahlqvist SR. Source: The Journal of Rheumatology. 2001 December; 28(12): 2597-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764203&dopt=Abstract
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Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis. Author(s): Prahalad S, Shear ES, Thompson SD, Giannini EH, Glass DN. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1851-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124869&dopt=Abstract
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Increased thickness of the arterial intima-media detected by ultrasonography in patients with rheumatoid arthritis. Author(s): Kumeda Y, Inaba M, Goto H, Nagata M, Henmi Y, Furumitsu Y, Ishimura E, Inui K, Yutani Y, Miki T, Shoji T, Nishizawa Y. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1489-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115178&dopt=Abstract
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Indian guidelines for the management of rheumatoid arthritis. Author(s): Lele RD. Source: J Assoc Physicians India. 2003 January; 51: 93-4; Author Reply 94. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693480&dopt=Abstract
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Induction of p16 at sites of cartilage invasion in the SCID mouse coimplantation model of rheumatoid arthritis. Author(s): Kuenzler P, Kuchen S, Rihoskova V, Michel BA, Gay RE, Neidhart M, Gay S, Seemayer CA. Source: Arthritis and Rheumatism. 2003 July; 48(7): 2069-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847703&dopt=Abstract
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Infections and biological therapy in rheumatoid arthritis. Author(s): Cunnane G, Doran M, Bresnihan B. Source: Best Practice & Research. Clinical Rheumatology. 2003 April; 17(2): 345-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787529&dopt=Abstract
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Infectious complications of biologic treatments of rheumatoid arthritis. Author(s): Mohan AK, Cote TR, Siegel JN, Braun MM. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 179-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707568&dopt=Abstract
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Inflammatory mediators and radiographic changes in temporomandibular joints of patients with rheumatoid arthritis. Author(s): Voog U, Alstergren P, Eliasson S, Leibur E, Kallikorm R, Kopp S. Source: Acta Odontologica Scandinavica. 2003 February; 61(1): 57-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635783&dopt=Abstract
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Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis. Author(s): Boers M, Nurmohamed MT, Doelman CJ, Lard LR, Verhoeven AC, Voskuyl AE, Huizinga TW, van de Stadt RJ, Dijkmans BA, van der Linden S. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 842-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922956&dopt=Abstract
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Influence of therapy with chimeric monoclonal tumour necrosis factor-alpha antibodies on intracellular cytokine profiles of T lymphocytes and monocytes in rheumatoid arthritis patients. Author(s): Schuerwegh AJ, Van Offel JF, Stevens WJ, Bridts CH, De Clerck LS. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 541-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649401&dopt=Abstract
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Informed consent in a clinical trial of a novel treatment for rheumatoid arthritis. Author(s): Criscione LG, Sugarman J, Sanders L, Pisetsky DS, St Clair EW. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 361-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794792&dopt=Abstract
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Infrared spectroscopy: shedding light on synovitis in patients with rheumatoid arthritis. Author(s): Canvin JM, Bernatsky S, Hitchon CA, Jackson M, Sowa MG, Mansfield JR, Eysel HH, Mantsch HH, El-Gabalawy HS. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509617&dopt=Abstract
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Inhibition of interleukin 10 signaling after Fc receptor ligation and during rheumatoid arthritis. Author(s): Ji JD, Tassiulas I, Park-Min KH, Aydin A, Mecklenbrauker I, Tarakhovsky A, Pricop L, Salmon JE, Ivashkiv LB. Source: The Journal of Experimental Medicine. 2003 June 2; 197(11): 1573-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782719&dopt=Abstract
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Inhibitors of p38 mitogen-activated protein kinase for the treatment of rheumatoid arthritis. Author(s): Pargellis C, Regan J. Source: Curr Opin Investig Drugs. 2003 May; 4(5): 566-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833650&dopt=Abstract
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Innate immunity as a hired gun: but is it rheumatoid arthritis? Author(s): Corr M, Firestein GS. Source: The Journal of Experimental Medicine. 2002 April 15; 195(8): F33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956300&dopt=Abstract
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Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Author(s): Wilder RL. Source: Annals of the Rheumatic Diseases. 2002 November; 61 Suppl 2: Ii96-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379637&dopt=Abstract
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Interactions between children with juvenile rheumatoid arthritis and their mothers. Author(s): Power TG, Dahlquist LM, Thompson SM, Warren R. Source: Journal of Pediatric Psychology. 2003 April-May; 28(3): 213-21. Erratum In: J Pediatr Psychol. 2003 July-August; 28(5): Following Page 373. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654947&dopt=Abstract
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Interferon gamma gene polymorphism and susceptibility to, and severity of, rheumatoid arthritis. Author(s): Constantin A, Navaux F, Lauwers-Cances V, Abbal M, van Meerwijk JP, Mazieres B, Cambon-Thomsen A, Cantagrel A. Source: Lancet. 2001 December 15; 358(9298): 2051-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755617&dopt=Abstract
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Interferon-beta for treatment of rheumatoid arthritis? Author(s): van Holten J, Plater-Zyberk C, Tak PP. Source: Arthritis Research. 2002; 4(6): 346-52. Epub 2002 September 18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453310&dopt=Abstract
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Interferon-gamma-induced calcium influx in T lymphocytes of multiple sclerosis and rheumatoid arthritis patients: a complementary mechanism for T cell activation? Author(s): Buntinx M, Ameloot M, Steels P, Janssen P, Medaer R, Geusens P, Raus J, Stinissen P. Source: Journal of Neuroimmunology. 2002 March; 124(1-2): 70-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958824&dopt=Abstract
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Interleukin 1 or tumor necrosis factor-alpha: which is the real target in rheumatoid arthritis? Author(s): Dayer JM. Source: J Rheumatol Suppl. 2002 September; 65: 10-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236616&dopt=Abstract
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Interleukin 1 receptor antagonist anakinra improves functional status in patients with rheumatoid arthritis. Author(s): Cohen SB, Woolley JM, Chan W; Anakinra 960180 Study Group. Source: The Journal of Rheumatology. 2003 February; 30(2): 225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563672&dopt=Abstract
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Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. Author(s): van Roon J, Wijngaarden S, Lafeber FP, Damen C, van de Winkel J, Bijlsma JW. Source: The Journal of Rheumatology. 2003 April; 30(4): 648-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672180&dopt=Abstract
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Interleukin 7 stimulates tumour necrosis factor alpha and Th1 cytokine production in joints of patients with rheumatoid arthritis. Author(s): van Roon JA, Glaudemans KA, Bijlsma JW, Lafeber FP. Source: Annals of the Rheumatic Diseases. 2003 February; 62(2): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525379&dopt=Abstract
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Interleukin-10 expression: is there a neglected contribution of CD8+ T cells in rheumatoid arthritis joints? Author(s): Moller B, Nguyen TT, Kessler U, Kaltwasser JP, Hoelzer D, Ottmann OG. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 813-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508773&dopt=Abstract
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Interleukin-10 receptor expression in systemic lupus erythematosus and rheumatoid arthritis. Author(s): Cairns AP, Crockard AD, Bell AL. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673894&dopt=Abstract
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Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Author(s): Miossec P. Source: Arthritis and Rheumatism. 2003 March; 48(3): 594-601. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632409&dopt=Abstract
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Interleukin-2 levels are elevated in the bone marrow serum of patients with mutilanstype rheumatoid arthritis. Author(s): Kuroda T, Tanabe N, Sakatsume M, Nozawa S, Mitsuka T, Ishikawa H, Tohyama CT, Nakazono K, Murasawa A, Nakano M, Gejyo F. Source: Clinical Rheumatology. 2002 February; 21(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954879&dopt=Abstract
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Interobserver agreement in ultrasonography of the finger and toe joints in rheumatoid arthritis. Author(s): Szkudlarek M, Court-Payen M, Jacobsen S, Klarlund M, Thomsen HS, Ostergaard M. Source: Arthritis and Rheumatism. 2003 April; 48(4): 955-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687537&dopt=Abstract
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Interpreting radiographic data in rheumatoid arthritis. Author(s): Ory PA. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 597-604. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810418&dopt=Abstract
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Intravenous human recombinant tumor necrosis factor receptor p55-Fc IgG1 fusion protein Ro 45-2081 (lenercept): a double blind, placebo controlled dose-finding study in rheumatoid arthritis. Author(s): Rau R, Sander O, van Riel P, van de Putte L, Hasler F, Zaug M, Kneer J, van der Auwera P, Stevens RM; Rheumatology Group 791. Source: The Journal of Rheumatology. 2003 April; 30(4): 680-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672184&dopt=Abstract
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Is a long-term high-intensity exercise program effective and safe in patients with rheumatoid arthritis? Results of a randomized controlled trial. Author(s): de Jong Z, Munneke M, Zwinderman AH, Kroon HM, Jansen A, Ronday KH, van Schaardenburg D, Dijkmans BA, Van den Ende CH, Breedveld FC, Vliet Vlieland TP, Hazes JM. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2415-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130460&dopt=Abstract
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Is expression of intracellular citrullinated proteins in synovial tissue specific for rheumatoid arthritis? Comment on the article by Baeten et al. Author(s): Smeets TJ, Vossenaar ER, van Venrooij WJ, Tak PP. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2824-6; Author Reply 2826-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384951&dopt=Abstract
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Is methotrexate plus cyclosporine A a useful salvage therapy for rheumatoid arthritis patients unresponsive to other types of methotrexate combination treatment? Author(s): Lerin-Lozano C, Schnabel A, Erbsloh-Moller B, Gross WL. Source: Clin Exp Rheumatol. 2002 September-October; 20(5): 737. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412217&dopt=Abstract
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Is NF-kappaB a useful therapeutic target in rheumatoid arthritis? Author(s): Feldmann M, Andreakos E, Smith C, Bondeson J, Yoshimura S, Kiriakidis S, Monaco C, Gasparini C, Sacre S, Lundberg A, Paleolog E, Horwood NJ, Brennan FM, Foxwell BM. Source: Annals of the Rheumatic Diseases. 2002 November; 61 Suppl 2: Ii13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379614&dopt=Abstract
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Is soluble CD44 variant isoform 5 useful as a predicting factor and a parameter for long term observation in rheumatoid arthritis? Author(s): Skoumal M, Kolarz G, Haberhauer G, Feyertag J, Wottawa A. Source: Annals of the Rheumatic Diseases. 2002 November; 61(11): 1036-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379536&dopt=Abstract
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Is there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis? Author(s): Cannella AC, O'Dell JR. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 185-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707569&dopt=Abstract
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Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients? Author(s): Corominas H, Domenech M, Laiz A, Gich I, Geli C, Diaz C, de Cuevillas F, Moreno M, Vazquez G, Baiget M. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 40-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509611&dopt=Abstract
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Isokinetic evaluation of the knee in patients with rheumatoid arthritis. Author(s): Meireles SM, Oliveira LM, Andrade MS, Silva AC, Natour J. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 December; 69(6): 566-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537264&dopt=Abstract
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Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis. Author(s): Cao D, Malmstrom V, Baecher-Allan C, Hafler D, Klareskog L, Trollmo C. Source: European Journal of Immunology. 2003 January; 33(1): 215-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594850&dopt=Abstract
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Joint stiffness in a phantom limb: evidence of central nervous system involvement in rheumatoid arthritis. Author(s): Haigh RC, McCabe CS, Halligan PW, Blake DR. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 888-92. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730550&dopt=Abstract
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Juvenile rheumatoid arthritis (juvenile chronic arthritis). Author(s): Alexiades-Armenakas M. Source: Dermatology Online Journal [electronic Resource]. 2001 December; 7(2): 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165235&dopt=Abstract
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Juvenile rheumatoid arthritis with amyloid goiter: report of a case with review of the literature. Author(s): Srivastava A, Baxi M, Yadav S, Agarwal A, Gupta RK, Misra SK, Mithal A. Source: Endocrine Pathology. 2001 Winter; 12(4): 437-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11914477&dopt=Abstract
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Juvenile rheumatoid arthritis. Author(s): Schneider R, Passo MH. Source: Rheumatic Diseases Clinics of North America. 2002 August; 28(3): 503-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380368&dopt=Abstract
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Juvenile rheumatoid arthritis: a guide for pediatricians. Author(s): Jarvis JN. Source: Pediatric Annals. 2002 July; 31(7): 437-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149797&dopt=Abstract
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Juvenile rheumatoid arthritis: therapeutic perspectives. Author(s): Chikanza IC. Source: Paediatric Drugs. 2002; 4(5): 335-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994038&dopt=Abstract
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Kallikreins and kininogens in saliva and plasma of patients presenting with rheumatoid arthritis. Author(s): Hernandez CC, Donadi EA, Reis ML. Source: Scandinavian Journal of Rheumatology. 2002; 31(1): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924648&dopt=Abstract
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Kaposi's sarcoma in an elderly patient with rheumatoid arthritis after intra-articular corticosteroids. Author(s): Burnet SP, McNeil JD. Source: Rheumatology (Oxford, England). 2002 January; 41(1): 107-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11792889&dopt=Abstract
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Key randomized trials of single agents in early rheumatoid arthritis. Author(s): van de Putte LB. Source: J Rheumatol Suppl. 2002 November; 66: 13-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435164&dopt=Abstract
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Laboratory changes on anti-tumor necrosis factor treatment in rheumatoid arthritis. Author(s): Ziolkowska M, Maslinski W. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 267-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707580&dopt=Abstract
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Laboratory testing in rheumatoid arthritis patients taking disease-modifying antirheumatic drugs: clinical evaluation and cost analysis. Author(s): Aletaha D, Smolen JS. Source: Arthritis and Rheumatism. 2002 April 15; 47(2): 181-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954012&dopt=Abstract
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Lack of association between -384 and 114 IL-2 gene polymorphisms and rheumatoid arthritis. Author(s): Fedetz M, Matesanz F, Caliz R, Ferrer MA, Collado MD, Alcina A, Martin J. Source: The Journal of Rheumatology. 2003 March; 30(3): 435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610796&dopt=Abstract
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Lack of association of Human T-cell lymphotrophic virus type 1(HTLV-1) infection and rheumatoid arthritis in an endemic area. Author(s): Sebastian D, Nayiager S, York DY, Mody GM. Source: Clinical Rheumatology. 2003 February; 22(1): 30-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605314&dopt=Abstract
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Large geodes in rheumatoid arthritis without joint destruction. Author(s): Rabar D, Crozes P, Lernoud M, Meignan F. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 December; 69(6): 617-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537273&dopt=Abstract
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Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Author(s): Sanders S, Harisdangkul V. Source: The American Journal of the Medical Sciences. 2002 April; 323(4): 190-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003373&dopt=Abstract
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Leflunomide for the treatment of rheumatoid arthritis. Author(s): Miceli-Richard C, Dougados M. Source: Expert Opinion on Pharmacotherapy. 2003 June; 4(6): 987-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783594&dopt=Abstract
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Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. Author(s): Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. Source: The Journal of Rheumatology. 2003 June; 30(6): 1182-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784387&dopt=Abstract
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Leflunomide for treating rheumatoid arthritis. Author(s): Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. Source: Cochrane Database Syst Rev. 2003; (1): Cd002047. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535423&dopt=Abstract
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Leflunomide in treatment of rheumatoid arthritis. Author(s): McCarey DW, Capell HA, Madhok R. Source: Lancet. 2002 March 30; 359(9312): 1158. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11943298&dopt=Abstract
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Lethal medium-vessel panarteritis mimicking deep sepsis following etanercept and minocycline therapy in a patient with severe rheumatoid arthritis. Author(s): Berthelot JM, Glemarec J, Maugars Y, Prost A. Source: Rheumatology (Oxford, England). 2002 June; 41(6): 703-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12048303&dopt=Abstract
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Leukocyte protein calprotectin and outcome in rheumatoid arthritis. A longitudinal study. Author(s): Madland TM, Hordvik M, Haga HJ, Jonsson R, Brun JG. Source: Scandinavian Journal of Rheumatology. 2002; 31(6): 351-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492250&dopt=Abstract
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Levels of antioxidant proteins and soluble intercellular adhesion molecule-1 in serum of patients with rheumatoid arthritis. Author(s): Cogalgil S, Taysi S. Source: Ann Clin Lab Sci. 2002 Summer; 32(3): 264-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175089&dopt=Abstract
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Liaison between rheumatoid arthritis and ulcerative colitis. Author(s): Aydin Y, Ozcakar L, Yildiz M, Akinci A. Source: Rheumatology International. 2003 January; 23(1): 47-8. Epub 2002 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548442&dopt=Abstract
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Life-threatening reversible bone marrow toxicity in a rheumatoid arthritis patient switched from leflunomide to infliximab. Author(s): Marchesoni A, Arreghini M, Panni B, Battafarano N, Uziel L. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 193-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509641&dopt=Abstract
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Light and electron microscopic analysis of liver biopsy samples from rheumatoid arthritis patients receiving long-term methotrexate therapy. Author(s): Ros S, Juanola X, Condom E, Canas C, Riera J, Guardiola J, Del Blanco J, Rebasa P, Valverde J, Roig-Escofet O. Source: Scandinavian Journal of Rheumatology. 2002; 31(6): 330-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492247&dopt=Abstract
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Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis. Author(s): Taysi S, Polat F, Gul M, Sari RA, Bakan E. Source: Rheumatology International. 2002 March; 21(5): 200-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958437&dopt=Abstract
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Lipid profile in rheumatoid arthritis and its relation to disease activity. Author(s): Vottery R, Saigal R, Singhal N, Gupta BS. Source: J Assoc Physicians India. 2001 December; 49: 1188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996442&dopt=Abstract
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Living with rheumatoid arthritis: expenditures, health status, and social impact on patients. Author(s): Lapsley HM, March LM, Tribe KL, Cross MJ, Courtenay BG, Brooks PM; Arthritis Cost and Outcome Project Group. Source: Annals of the Rheumatic Diseases. 2002 September; 61(9): 818-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176807&dopt=Abstract
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Local production of complement proteins in rheumatoid arthritis synovium. Author(s): Neumann E, Barnum SR, Tarner IH, Echols J, Fleck M, Judex M, Kullmann F, Mountz JD, Scholmerich J, Gay S, Muller-Ladner U. Source: Arthritis and Rheumatism. 2002 April; 46(4): 934-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953970&dopt=Abstract
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Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies. Author(s): Steenbakkers PG, Baeten D, Rovers E, Veys EM, Rijnders AW, Meijerink J, De Keyser F, Boots AM. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 June 1; 170(11): 5719-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759455&dopt=Abstract
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Localized cortical bone absorption induced by cubital bursitis in rheumatoid arthritis. Author(s): Taira H, Yoshida S, Takasita M, Tsumura H, Torisu T. Source: Orthopedics. 2002 August; 25(8): 860-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195916&dopt=Abstract
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Long term anti-tumour necrosis factor alpha monotherapy in rheumatoid arthritis: effect on radiological course and prognostic value of markers of cartilage turnover and endothelial activation. Author(s): den Broeder AA, Joosten LA, Saxne T, Heinegard D, Fenner H, Miltenburg AM, Frasa WL, van Tits LJ, Buurman WA, van Riel PL, van de Putte LB, Barrera P. Source: Annals of the Rheumatic Diseases. 2002 April; 61(4): 311-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874832&dopt=Abstract
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Long term efficacy and safety of cyclosporin versus parenteral gold in early rheumatoid arthritis: a three year study of radiographic progression, renal function, and arterial hypertension. Author(s): Kvien TK, Zeidler HK, Hannonen P, Wollheim FA, Forre O, Hafstrom I, Kaltwasser JP, Leirisalo-Repo M, Manger B, Laasonen L, Prestele H, Kurki P. Source: Annals of the Rheumatic Diseases. 2002 June; 61(6): 511-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006323&dopt=Abstract
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Long term structural effects of combination therapy in patients with early rheumatoid arthritis: five year follow up of a prospective double blind controlled study. Author(s): Maillefert JF, Combe B, Goupille P, Cantagrel A, Dougados M. Source: Annals of the Rheumatic Diseases. 2003 August; 62(8): 764-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860733&dopt=Abstract
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Longitudinal measurement of methotrexate liver concentrations does not correlate with liver damage, clinical efficacy, or toxicity during a 3.5 year double blind study in rheumatoid arthritis. Author(s): Fathi NH, Mitros F, Hoffman J, Straniero N, Labreque D, Koehnke R, Furst DE. Source: The Journal of Rheumatology. 2002 October; 29(10): 2092-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375317&dopt=Abstract
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Longitudinal radiographic analysis of rheumatoid arthritis in the hand and wrist. Author(s): Leak RS, Rayan GM, Arthur RE. Source: The Journal of Hand Surgery. 2003 May; 28(3): 427-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772099&dopt=Abstract
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Long-term anti-tumor necrosis factor antibody therapy in rheumatoid arthritis patients sensitizes the pituitary gland and favors adrenal androgen secretion. Author(s): Straub RH, Pongratz G, Scholmerich J, Kees F, Schaible TF, Antoni C, Kalden JR, Lorenz HM. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1504-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794817&dopt=Abstract
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Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, openlabel, extended-treatment trial. Author(s): Lovell DJ, Giannini EH, Reiff A, Jones OY, Schneider R, Olson JC, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Lange M, Finck BK, Burge DJ; Pediatric Rheumatology Collaborative Study Group. Source: Arthritis and Rheumatism. 2003 January; 48(1): 218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528122&dopt=Abstract
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Long-term efficacy of a cognitive behavioural treatment from a randomized controlled trial for patients recently diagnosed with rheumatoid arthritis. Author(s): Sharpe L, Sensky T, Timberlake N, Ryan B, Allard S. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 435-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626793&dopt=Abstract
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Long-term follow-up of intra-articular injections into the temporomandibular joint in patients with rheumatoid arthritis. Author(s): Vallon D, Akerman S, Nilner M, Petersson A. Source: Swed Dent J. 2002; 26(4): 149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611144&dopt=Abstract
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Long-term follow-up of systemic reactive AA amyloidosis secondary to rheumatoid arthritis: successful treatment with intermediate-dose corticosteroid. Author(s): Matsuda M, Morita H, Ikeda S. Source: Intern Med. 2002 May; 41(5): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058893&dopt=Abstract
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Long-term morbidity, mortality, and economics of rheumatoid arthritis. Author(s): Wong JB, Ramey DR, Singh G. Source: Arthritis and Rheumatism. 2001 December; 44(12): 2746-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762934&dopt=Abstract
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Long-term observation study of Austrian patients with rheumatoid arthritis. Author(s): Skoumal M, Wottawa A. Source: Acta Medica Austriaca. 2002; 29(2): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050946&dopt=Abstract
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Long-term outcome in rheumatoid arthritis: a simple algorithm of baseline parameters can predict radiographic damage, disability, and disease course at 12-year followup. Author(s): Drossaers-Bakker KW, Zwinderman AH, Vlieland TP, Van Zeben D, Vos K, Breedveld FC, Hazes JM. Source: Arthritis and Rheumatism. 2002 Aug15; 47(4): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209484&dopt=Abstract
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Longterm predictors of anxiety and depressed mood in early rheumatoid arthritis: a 3 and 5 year followup. Author(s): Evers AW, Kraaimaat FW, Geenen R, Jacobs JW, Bijlsma JW. Source: The Journal of Rheumatology. 2002 November; 29(11): 2327-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415588&dopt=Abstract
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Long-term remission of an EBV-positive B cell lymphoproliferative disorder associated with rheumatoid arthritis under methotrexate with anti-CD20 monoclonal antibody (Rituximab) monotherapy. Author(s): Kelaidi C, Tulliez M, Lecoq-Lafon C, Pham XV, Kahan A, Dreyfus F, Bouscary D. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 October; 16(10): 2173-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357380&dopt=Abstract
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Long-term results of arthroscopic synovectomy for seropositive rheumatoid arthritis: 6-16 year review. Author(s): Gibbons CE, Gosal HS, Bartlett J. Source: International Orthopaedics. 2002; 26(2): 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078886&dopt=Abstract
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Long-term safety and maintenance of clinical improvement following treatment with anakinra (recombinant human interleukin-1 receptor antagonist) in patients with rheumatoid arthritis: extension phase of a randomized, double-blind, placebocontrolled trial. Author(s): Nuki G, Bresnihan B, Bear MB, McCabe D; European Group Of Clinical Investigators. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2838-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428223&dopt=Abstract
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Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritis. Author(s): Rinaldi N, Willhauck M, Weis D, Brado B, Kern P, Lukoschek M, SchwarzEywill M, Barth TF. Source: Virchows Archiv : an International Journal of Pathology. 2001 November; 439(5): 675-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764389&dopt=Abstract
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Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis synovium. Author(s): Catrina AI, Ulfgren AK, Lindblad S, Grondal L, Klareskog L. Source: Annals of the Rheumatic Diseases. 2002 October; 61(10): 934-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228167&dopt=Abstract
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Low physical activity reduces total energy expenditure in women with rheumatoid arthritis: implications for dietary intake recommendations. Author(s): Roubenoff R, Walsmith J, Lundgren N, Snydman L, Dolnikowski GJ, Roberts S. Source: The American Journal of Clinical Nutrition. 2002 October; 76(4): 774-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324290&dopt=Abstract
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Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders. Author(s): Matsumoto I, Lee DM, Goldbach-Mansky R, Sumida T, Hitchon CA, Schur PH, Anderson RJ, Coblyn JS, Weinblatt ME, Brenner M, Duclos B, Pasquali JL, ElGabalawy H, Mathis D, Benoist C. Source: Arthritis and Rheumatism. 2003 April; 48(4): 944-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687536&dopt=Abstract
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Low-dose glucocorticoids in early rheumatoid arthritis: discordant effects on bone mineral density and fractures? Author(s): van Everdingen AA, Siewertsz van Reesema DR, Jacobs JW, Bijlsma JW. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747268&dopt=Abstract
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Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Author(s): van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, Bijlsma JW. Source: Annals of Internal Medicine. 2002 January 1; 136(1): 1-12. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777359&dopt=Abstract
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Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Author(s): Watson DJ, Rhodes T, Cai B, Guess HA. Source: Archives of Internal Medicine. 2002 May 27; 162(10): 1105-10. Erratum In: Arch Intern Med 2002 August 12-26; 162(15): 1779. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020179&dopt=Abstract
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Lymphoepithelioma-like carcinoma of the parotid gland in a patient with rheumatoid arthritis. Author(s): Mok MY, Shek WH, Wong RW. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 848-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508780&dopt=Abstract
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Lymphoma subtypes in patients with rheumatoid arthritis: increased proportion of diffuse large B cell lymphoma. Author(s): Baecklund E, Sundstrom C, Ekbom A, Catrina AI, Biberfeld P, Feltelius N, Klareskog L. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1543-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794821&dopt=Abstract
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Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Author(s): Mariette X, Cazals-Hatem D, Warszawki J, Liote F, Balandraud N, Sibilia J; Investigators of the Club Rhumatismes et Inflammation. Source: Blood. 2002 June 1; 99(11): 3909-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010788&dopt=Abstract
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Lysosomal peptidases and glycosidases in rheumatoid arthritis. Author(s): Sohar N, Hammer H, Sohar I. Source: Biological Chemistry. 2002 May; 383(5): 865-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108554&dopt=Abstract
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Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis. Author(s): Ramanan AV, Schneider R. Source: The Journal of Rheumatology. 2003 February; 30(2): 401-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563702&dopt=Abstract
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Macrophage migration inhibitory factor: an emerging therapeutic target in rheumatoid arthritis. Author(s): Morand EF, Bucala R, Leech M. Source: Arthritis and Rheumatism. 2003 February; 48(2): 291-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571836&dopt=Abstract
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Magnetic resonance imaging appearance of the hands and feet in patients with early rheumatoid arthritis. Author(s): Boutry N, Larde A, Lapegue F, Solau-Gervais E, Flipo RM, Cotten A. Source: The Journal of Rheumatology. 2003 April; 30(4): 671-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672183&dopt=Abstract
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Magnetic resonance imaging in the evaluation of bone damage in rheumatoid arthritis: a more precise image or just a more expensive one? Author(s): Goldbach-Mansky R, Woodburn J, Yao L, Lipsky PE. Source: Arthritis and Rheumatism. 2003 March; 48(3): 585-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632407&dopt=Abstract
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Magnetic resonance imaging of the fifth metatarsophalangeal joint compared with conventional radiography in patients with early rheumatoid arthritis. Author(s): Forslind K, Johanson A, Larsson EM, Svensson B. Source: Scandinavian Journal of Rheumatology. 2003; 32(3): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892248&dopt=Abstract
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Maintaining wrist function in severe rheumatoid arthritis: a case study of revision Swanson wrist arthroplasty staged via a wrist fusion in rheumatoid arthritis. Author(s): Mutimer JN, Giddins GE. Source: Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2002 December; 7(2): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596276&dopt=Abstract
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Major differences in antigen-processing correlate with a single Arg71<-->Lys substitution in HLA-DR molecules predisposing to rheumatoid arthritis and with their selective interactions with 70-kDa heat shock protein chaperones. Author(s): Roth S, Willcox N, Rzepka R, Mayer MP, Melchers I. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 September 15; 169(6): 301520. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218116&dopt=Abstract
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Management of a patient with active rheumatoid arthritis and suspected tuberculosis causing effusive-constrictive pericarditis. Author(s): Yildiz M, Erdogan O, Aktoz M, Gul C, Ozbay G. Source: International Journal of Cardiology. 2003 May; 89(1): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727018&dopt=Abstract
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Management of glucocorticoid-induced osteoporosis in patients with rheumatoid arthritis: rates and predictors of care in an academic rheumatology practice. Author(s): Solomon DH, Katz JN, Jacobs JP, La Tourette AM, Coblyn J. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483716&dopt=Abstract
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Manganese superoxide dismutase, glutathione peroxidase, and total radical trapping antioxidant capacity in active rheumatoid arthritis. Author(s): De Leo ME, Tranghese A, Passantino M, Mordente A, Lizzio MM, Galeotti T, Zoli A. Source: The Journal of Rheumatology. 2002 October; 29(10): 2245-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375348&dopt=Abstract
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Mass spectrometric proteome analyses of synovial fluids and plasmas from patients suffering from rheumatoid arthritis and comparison to reactive arthritis or osteoarthritis. Author(s): Sinz A, Bantscheff M, Mikkat S, Ringel B, Drynda S, Kekow J, Thiesen HJ, Glocker MO. Source: Electrophoresis. 2002 September; 23(19): 3445-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373775&dopt=Abstract
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Mast cells as a target of rheumatoid arthritis treatment. Author(s): Kobayashi Y, Okunishi H. Source: Japanese Journal of Pharmacology. 2002 September; 90(1): 7-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396022&dopt=Abstract
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MCID/Low Disease Activity State Workshop: low disease activity state in rheumatoid arthritis. Author(s): Wells G, Boers M, Shea B, Anderson J, Felson D, Johnson K, Kirwan J, Lassere M, Robinson V, Simon L, Strand V, van Riel P, Tugwell P. Source: The Journal of Rheumatology. 2003 May; 30(5): 1110-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734918&dopt=Abstract
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Measurement of soluble Fcgamma receptor type IIIa derived from macrophages in plasma: increase in patients with rheumatoid arthritis. Author(s): Masuda M, Morimoto T, Kobatake S, Nishimura N, Nakamoto K, Dong XH, Komiyama Y, Ogawa R, Takahashi H. Source: Clinical and Experimental Immunology. 2003 June; 132(3): 477-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780696&dopt=Abstract
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Measuring the meaning of disability in rheumatoid arthritis: the Personal Impact Health Assessment Questionnaire (PI HAQ). Author(s): Hewlett S, Smith AP, Kirwan JR. Source: Annals of the Rheumatic Diseases. 2002 November; 61(11): 986-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379521&dopt=Abstract
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Mechanical wearing down of flexor tendons in rheumatoid arthritis as a result of extreme volar-flexed intercalated segment instability. Author(s): Baer W, Dumont CE. Source: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery / Nordisk Plastikkirurgisk Forening [and] Nordisk Klubb for Handkirurgi. 2002; 36(3): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141211&dopt=Abstract
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Mechanisms of corticosteroid resistance in rheumatoid arthritis: a putative role for the corticosteroid receptor beta isoform. Author(s): Chikanza IC. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 39-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114257&dopt=Abstract
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Mediators of inflammation are down-regulated while apoptosis is up-regulated in rheumatoid arthritis synovial tissue by polymerized collagen. Author(s): Furuzawa-Carballeda J, Rodriquez-Calderon R, Diaz de Leon L, AlcocerVarela J. Source: Clinical and Experimental Immunology. 2002 October; 130(1): 140-9. Erratum In: Clin Exp Immunol 2002 December; 130(3): 565-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296865&dopt=Abstract
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Medicoeconomic evaluations in rheumatology--the example of rheumatoid arthritis. Author(s): Maravic M, Daures JP, Sany J. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 October; 69(5): 419-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477223&dopt=Abstract
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Melatonin in rheumatoid arthritis: a disease-promoting and modulating hormone? Author(s): Maestroni GJ, Sulli A, Pizzorni C, Villaggio B, Cutolo M. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 872-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508787&dopt=Abstract
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Melatonin in rheumatoid arthritis: synovial macrophages show melatonin receptors. Author(s): Maestroni GJ, Sulli A, Pizzorni C, Villaggio B, Cutolo M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 271-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114283&dopt=Abstract
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Melatonin serum levels in rheumatoid arthritis. Author(s): Sulli A, Maestroni GJ, Villaggio B, Hertens E, Craviotto C, Pizzorni C, Briata M, Seriolo B, Cutolo M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 276-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114284&dopt=Abstract
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Meta-analysis of four rheumatoid arthritis genome-wide linkage studies: confirmation of a susceptibility locus on chromosome 16. Author(s): Fisher SA, Lanchbury JS, Lewis CM. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1200-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746892&dopt=Abstract
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Metacarpophalangeal arthroplasty in rheumatoid arthritis: what determines satisfaction with surgery? Author(s): Mandl LA, Galvin DH, Bosch JP, George CC, Simmons BP, Axt TS, Fossel AH, Katz JN. Source: The Journal of Rheumatology. 2002 December; 29(12): 2488-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465140&dopt=Abstract
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Metacarpophalangeal joint arthroplasty in rheumatoid arthritis. Author(s): Abboud JA, Beredjiklian PK, Bozentka DJ. Source: J Am Acad Orthop Surg. 2003 May-June; 11(3): 184-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828448&dopt=Abstract
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Metacarpophalangeal joint arthroplasty in rheumatoid arthritis. Author(s): Kimball HL, Terrono AL, Feldon P, Zelouf DS. Source: Instr Course Lect. 2003; 52: 163-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690846&dopt=Abstract
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Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Author(s): Choi HK, Hernan MA, Seeger JD, Robins JM, Wolfe F. Source: Lancet. 2002 April 6; 359(9313): 1173-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955534&dopt=Abstract
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Methotrexate in the treatment of rheumatoid arthritis. I. In vitro effects on cells of the osteoblast lineage. Author(s): Minaur NJ, Jefferiss C, Bhalla AK, Beresford JN. Source: Rheumatology (Oxford, England). 2002 July; 41(7): 735-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096221&dopt=Abstract
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Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density. Author(s): Minaur NJ, Kounali D, Vedi S, Compston JE, Beresford JN, Bhalla AK. Source: Rheumatology (Oxford, England). 2002 July; 41(7): 741-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096222&dopt=Abstract
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Methotrexate pneumonitis after initiation of infliximab therapy for rheumatoid arthritis. Author(s): Kramer N, Chuzhin Y, Kaufman LD, Ritter JM, Rosenstein ED. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 670-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522843&dopt=Abstract
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Methotrexate pneumonitis in a patient with rheumatoid arthritis. Author(s): Hsu PC, Lan JL, Hsieh TY, Jan YJ, Huang WN. Source: J Microbiol Immunol Infect. 2003 June; 36(2): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886966&dopt=Abstract
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Methotrexate treatment and mortality in rheumatoid arthritis. Author(s): Rewald E, de las Mercedes Francischetti M. Source: Lancet. 2002 October 5; 360(9339): 1097. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384012&dopt=Abstract
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Methotrexate treatment and mortality in rheumatoid arthritis. Author(s): Sibilia J, Mariette X. Source: Lancet. 2002 October 5; 360(9339): 1096-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384011&dopt=Abstract
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Methotrexate treatment and mortality in rheumatoid arthritis. Author(s): Troger U, Bode-Boger SM. Source: Lancet. 2002 October 5; 360(9339): 1096; Author Reply 1097-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384010&dopt=Abstract
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Methotrexate treatment and mortality in rheumatoid arthritis. Author(s): Landewe RB, Breedveld FC, Dijkmans BA. Source: Lancet. 2002 October 5; 360(9339): 1095-6; Author Reply 1097-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384009&dopt=Abstract
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Methotrexate treatment and mortality in rheumatoid arthritis. Author(s): Slot O. Source: Lancet. 2002 October 5; 360(9339): 1095; Author Reply 1097-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384008&dopt=Abstract
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Methotrexate twice weekly vs once weekly in rheumatoid arthritis: a pilot doubleblind, controlled study. Author(s): Pandya S, Aggarwal A, Misra R. Source: Rheumatology International. 2002 May; 22(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120905&dopt=Abstract
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Methotrexate, hydroxychloroquine, and intramuscular gold in rheumatoid arthritis: relative area under the curve effectiveness and sequence effects. Author(s): Hurst S, Kallan MJ, Wolfe FJ, Fries JF, Albert DA. Source: The Journal of Rheumatology. 2002 August; 29(8): 1639-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180722&dopt=Abstract
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Micromotion of the Souter-Strathclyde total elbow prosthesis in patients with rheumatoid arthritis 21 elbows followed for 2 years. Author(s): Valstar ER, Garling EH, Rozing PM. Source: Acta Orthopaedica Scandinavica. 2002 June; 73(3): 264-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143970&dopt=Abstract
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Microsatellite instability and suppressed DNA repair enzyme expression in rheumatoid arthritis. Author(s): Lee SH, Chang DK, Goel A, Boland CR, Bugbee W, Boyle DL, Firestein GS. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 February 15; 170(4): 221420. Erratum In: J Immunol. 2003 May 1; 170(9): 4869. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574395&dopt=Abstract
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Migration of CX3CR1-positive T cells producing type 1 cytokines and cytotoxic molecules into the synovium of patients with rheumatoid arthritis. Author(s): Nanki T, Imai T, Nagasaka K, Urasaki Y, Nonomura Y, Taniguchi K, Hayashida K, Hasegawa J, Yoshie O, Miyasaka N. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2878-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428227&dopt=Abstract
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Mitral valve surgery in a patient with rheumatoid arthritis being treated with methotrexate. Author(s): Takami Y, Ina H. Source: Jpn J Thorac Cardiovasc Surg. 2003 May; 51(5): 205-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776953&dopt=Abstract
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Mode of inheritance of HLA-DRB1 shared epitope in Japanese familial rheumatoid arthritis. Author(s): Takeuchi F, Mori M, Goto M, Matsuta K, Yamada A, Chihara T, Hanyu T, Murayama T, Yamamoto S, Takubo N, Murata N, Matsubara T, Itakura M, Sakuta H. Source: Clin Exp Rheumatol. 2002 May-June; 20(3): 395-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102478&dopt=Abstract
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Modeling the progression of rheumatoid arthritis: a two-country model to estimate costs and consequences of rheumatoid arthritis. Author(s): Kobelt G, Jonsson L, Lindgren P, Young A, Eberhardt K. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2310-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355478&dopt=Abstract
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Modified disease activity score versus radiologic progression as an indicator of rheumatoid arthritis disease status: comment on the article by Landewe et al. Author(s): McEntegart A, Madhok R. Source: Arthritis and Rheumatism. 2003 January; 48(1): 272; Author Reply 272-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528133&dopt=Abstract
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Modified Larsen scoring of digitized radiographs in rheumatoid arthritis. Author(s): Young-Min SA, Shakhapur S, Marshall N, Griffiths I, Cawston T, Grainger A. Source: The Journal of Rheumatology. 2003 February; 30(2): 238-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563674&dopt=Abstract
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Molecular aspects of glucocorticoid hormone action in rheumatoid arthritis. Author(s): Neeck G, Renkawitz R, Eggert M. Source: Cytokines, Cellular & Molecular Therapy. 2002 December; 7(2): 61-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607796&dopt=Abstract
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Molecular heterogeneity of the SHAP-hyaluronan complex. Isolation and characterization of the complex in synovial fluid from patients with rheumatoid arthritis. Author(s): Yingsung W, Zhuo L, Morgelin M, Yoneda M, Kida D, Watanabe H, Ishiguro N, Iwata H, Kimata K. Source: The Journal of Biological Chemistry. 2003 August 29; 278(35): 32710-8. Epub 2003 June 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799384&dopt=Abstract
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Molecular profile of synovial fibroblasts in rheumatoid arthritis depends on the stage of proliferation. Author(s): Masuda K, Masuda R, Neidhart M, Simmen BR, Michel BA, Muller-Ladner U, Gay RE, Gay S. Source: Arthritis Research. 2002; 4(5): R8. Epub 2002 July 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223111&dopt=Abstract
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Monitoring methotrexate hepatic toxicity in rheumatoid arthritis: is it time to update the guidelines? Author(s): Yazici Y, Erkan D, Paget SA. Source: The Journal of Rheumatology. 2002 August; 29(8): 1586-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180713&dopt=Abstract
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Mononuclear cell response to enterobacteria and Gram-positive cell walls of normal intestinal microbiota in early rheumatoid arthritis and other inflammatory arthritides. Author(s): Chen T, Rimpilainen M, Luukkainen R, Mottonen T, Yli-Kerttula U, Saario R, Toivanen P. Source: Clin Exp Rheumatol. 2002 March-April; 20(2): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051398&dopt=Abstract
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Morbidity not increased in rheumatoid arthritis patient with profound lymphopenia following CD4 monoclonal antibody therapy: comment on the article by Isaacs et al. Author(s): Menon Y, Singh R, Cuchacovich R, Espinoza LR. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1973-4; Author Reply 1974. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124887&dopt=Abstract
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Morphological and molecular pathology of the B cell response in synovitis of rheumatoid arthritis. Author(s): Magalhaes R, Stiehl P, Morawietz L, Berek C, Krenn V. Source: Virchows Archiv : an International Journal of Pathology. 2002 November; 441(5): 415-27. Epub 2002 November 05. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447670&dopt=Abstract
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Mortality in patients with rheumatoid arthritis treated actively from the time of diagnosis. Author(s): Peltomaa R, Paimela L, Kautiainen H, Leirisalo-Repo M. Source: Annals of the Rheumatic Diseases. 2002 October; 61(10): 889-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228159&dopt=Abstract
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Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women's Health Study. Author(s): Mikuls TR, Saag KG, Criswell LA, Merlino LA, Kaslow RA, Shelton BJ, Cerhan JR. Source: Annals of the Rheumatic Diseases. 2002 November; 61(11): 994-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379522&dopt=Abstract
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Most patients receiving routine care for rheumatoid arthritis in 2001 did not meet inclusion criteria for most recent clinical trials or american college of rheumatology criteria for remission. Author(s): Sokka T, Pincus T. Source: The Journal of Rheumatology. 2003 June; 30(6): 1138-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784382&dopt=Abstract
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Motivation as a crucial predictor of good compliance in adolescents with rheumatoid arthritis. Author(s): Kyngas H. Source: International Journal of Nursing Practice. 2002 December; 8(6): 336-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390587&dopt=Abstract
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MR imaging assessment of clinical problems in rheumatoid arthritis. Author(s): Narvaez JA, Narvaez J, Roca Y, Aguilera C. Source: European Radiology. 2002 July; 12(7): 1819-28. Epub 2002 January 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111074&dopt=Abstract
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Multiple occlusive retinal arteritis in both eyes of a patient with rheumatoid arthritis. Author(s): Matsuo T. Source: Japanese Journal of Ophthalmology. 2001 November-December; 45(6): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754914&dopt=Abstract
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NADPH oxidase priming and p47phox phosphorylation in neutrophils from synovial fluid of patients with rheumatoid arthritis and spondylarthropathy. Author(s): El Benna J, Hayem G, Dang PM, Fay M, Chollet-Martin S, Elbim C, Meyer O, Gougerot-Pocidalo MA. Source: Inflammation. 2002 December; 26(6): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546136&dopt=Abstract
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Nails in the coffin: increasing evidence for the role of rheumatic disease in the cardiovascular mortality of rheumatoid arthritis. Author(s): Bacon PA, Townend JN. Source: Arthritis and Rheumatism. 2001 December; 44(12): 2707-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762929&dopt=Abstract
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National study of cause-specific mortality in rheumatoid arthritis, juvenile chronic arthritis, and other rheumatic conditions: a 20 year followup study. Author(s): Thomas E, Symmons DP, Brewster DH, Black RJ, Macfarlane GJ. Source: The Journal of Rheumatology. 2003 May; 30(5): 958-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734889&dopt=Abstract
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Natural killer cell dysfunction in patients with systemic-onset juvenile rheumatoid arthritis and macrophage activation syndrome. Author(s): Grom AA, Villanueva J, Lee S, Goldmuntz EA, Passo MH, Filipovich A. Source: The Journal of Pediatrics. 2003 March; 142(3): 292-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640378&dopt=Abstract
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Natural killer cells in the synovial fluid of rheumatoid arthritis patients exhibit a CD56bright,CD94bright,CD158negative phenotype. Author(s): Pridgeon C, Lennon GP, Pazmany L, Thompson RN, Christmas SE, Moots RJ. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 870-8. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730548&dopt=Abstract
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Necessary role of phosphatidylinositol 3-kinase in transforming growth factor betamediated activation of Akt in normal and rheumatoid arthritis synovial fibroblasts. Author(s): Kim G, Jun JB, Elkon KB. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1504-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115180&dopt=Abstract
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Necrotising fasciitis in a patient receiving infliximab for rheumatoid arthritis. Author(s): Chan AT, Cleeve V, Daymond TJ. Source: Postgraduate Medical Journal. 2002 January; 78(915): 47-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796874&dopt=Abstract
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Necrotizing fasciitis in a patient with rheumatoid arthritis. Author(s): McEntegart A, Capell HA. Source: Rheumatology (Oxford, England). 2002 July; 41(7): 828-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096238&dopt=Abstract
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Need and sequence of large joint replacements in rheumatoid arthritis. A 25-year follow-up study. Author(s): Palm TM, Kaarela K, Hakala MS, Kautiainen HJ, Kroger HP, Belt EA. Source: Clin Exp Rheumatol. 2002 May-June; 20(3): 392-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102477&dopt=Abstract
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Negative social perception of hypothetical workers with rheumatoid arthritis. Author(s): McQuade DV. Source: Journal of Behavioral Medicine. 2002 June; 25(3): 205-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055773&dopt=Abstract
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Nephrotic syndrome as a complication of anti-TNFalpha in a patient with rheumatoid arthritis. Author(s): den Broeder AA, Assmann KJ, van Riel PL, Wetzels JF. Source: The Netherlands Journal of Medicine. 2003 April; 61(4): 137-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852723&dopt=Abstract
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Nephrotic syndrome associated with anti-tumor necrosis factor alpha therapy in a patient with rheumatoid arthritis: comment on the article by Charles et al. Author(s): den Broeder AA, Assmann KJ, van Riel PL, Wetzels JF. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1691-3; Author Reply 1693. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115204&dopt=Abstract
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Neutrophil migration and production of reactive oxygen species during treatment with a fully human anti-tumor necrosis factor-alpha monoclonal antibody in patients with rheumatoid arthritis. Author(s): den Broeder AA, Wanten GJ, Oyen WJ, Naber T, van Riel PL, Barrera P. Source: The Journal of Rheumatology. 2003 February; 30(2): 232-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563673&dopt=Abstract
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New antibody approved for treatment of rheumatoid arthritis. Author(s): Piascik P. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2003 March-April; 43(2): 327-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688444&dopt=Abstract
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New concepts in the treatment of rheumatoid arthritis. Author(s): Goldbach-Mansky R, Lipsky PE. Source: Annual Review of Medicine. 2003; 54: 197-216. Epub 2001 December 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359827&dopt=Abstract
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New developments in imaging in rheumatoid arthritis. Author(s): Peterfy CG. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 288-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707583&dopt=Abstract
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New directions in symptomatic therapy for patients with osteoarthritis and rheumatoid arthritis. Author(s): Hochberg MC. Source: Seminars in Arthritis and Rheumatism. 2002 December; 32(3 Suppl 1): 4-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528069&dopt=Abstract
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New evidence for vascular disease in patients with early rheumatoid arthritis. Author(s): Kaplan MJ, McCune WJ. Source: Lancet. 2003 March 29; 361(9363): 1068-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672306&dopt=Abstract
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New onset systemic lupus erythematosus in a patient receiving etanercept for rheumatoid arthritis. Author(s): Cairns AP, Duncan MK, Hinder AE, Taggart AJ. Source: Annals of the Rheumatic Diseases. 2002 November; 61(11): 1031-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379532&dopt=Abstract
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New radiographic bone erosions in the wrists of patients with rheumatoid arthritis are detectable with magnetic resonance imaging a median of two years earlier. Author(s): Ostergaard M, Hansen M, Stoltenberg M, Jensen KE, Szkudlarek M, Pedersen-Zbinden B, Lorenzen I. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2128-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905465&dopt=Abstract
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New role for an old friend: prednisone is a disease-modifying agent in early rheumatoid arthritis. Author(s): Conn DL, Lim SS. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 193-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707570&dopt=Abstract
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Newer immunosuppressive drugs: their potential role in rheumatoid arthritis therapy. Author(s): Drosos AA. Source: Drugs. 2002; 62(6): 891-907. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929337&dopt=Abstract
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Newly diagnosed rheumatoid arthritis. Author(s): Weisman MH. Source: Annals of the Rheumatic Diseases. 2002 April; 61(4): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874827&dopt=Abstract
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NF-kappaB-dependent lymphocyte hyperadhesiveness to synovial fibroblasts by hypoxia and reoxygenation: potential role in rheumatoid arthritis. Author(s): Han MK, Kim JS, Park BH, Kim JR, Hwang BY, Lee HY, Song EK, Yoo WH. Source: Journal of Leukocyte Biology. 2003 April; 73(4): 525-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660227&dopt=Abstract
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No association of interleukin-4 gene polymorphisms in Chinese patients with rheumatoid arthritis in Taiwan. Author(s): Huang CM, Wu MC, Wu JY, Tsai FJ. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 871-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508786&dopt=Abstract
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No association of polymorphisms of the CTLA-4 exon 1(+49) and promoter(-318) genes with rheumatoid arthritis in the Korean population. Author(s): Lee YH, Choi SJ, Ji JD, Song GG. Source: Scandinavian Journal of Rheumatology. 2002; 31(5): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455815&dopt=Abstract
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No therapeutic effect of plasmin antagonist tranexamic acid in rheumatoid arthritis. A double-blind placebo-controlled pilot study. Author(s): van der Laan WH, Ronday HK, TeKoppele JM, Breedveld FC, Huizinga TW, Verheijen JH. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 359-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846058&dopt=Abstract
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Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLADRB1/TNF gene interaction. Author(s): Mattey DL, Dawes PT, Fisher J, Brownfield A, Thomson W, Hajeer AH, Ollier WE. Source: The Journal of Rheumatology. 2002 November; 29(11): 2313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415586&dopt=Abstract
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Nodular regenerative hyperplasia in a rheumatoid arthritis patient without felty's syndrome. Author(s): Goritsas C, Roussos A, Ferti A, Trigidou R. Source: Journal of Clinical Gastroenterology. 2002 October; 35(4): 363-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352307&dopt=Abstract
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Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. Author(s): Harney S, Newton J, Milicic A, Brown MA, Wordsworth BP. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 171-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509632&dopt=Abstract
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Noninvasive measurement of acceleration at the knee joint in patients with rheumatoid arthritis and spondyloarthropathy of the knee. Author(s): Reddy NP, Rothschild BM, Verrall E, Joshi A. Source: Annals of Biomedical Engineering. 2001 December; 29(12): 1106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11853263&dopt=Abstract
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Nonoperative management of functional hallux limitus in a patient with rheumatoid arthritis. Author(s): Shrader JA, Siegel KL. Source: Physical Therapy. 2003 September; 83(9): 831-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940769&dopt=Abstract
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Norepinephrine from synovial tyrosine hydroxylase positive cells is a strong indicator of synovial inflammation in rheumatoid arthritis. Author(s): Miller LE, Grifka J, Scholmerich J, Straub RH. Source: The Journal of Rheumatology. 2002 March; 29(3): 427-35. Erratum In: J Rheumatol. 2003 May; 30(5): 1125. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908553&dopt=Abstract
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Normal intestinal microbiota in the aetiopathogenesis of rheumatoid arthritis. Author(s): Toivanen P. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 807-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922950&dopt=Abstract
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Novel autoantibodies to pituitary gland specific factor 1a in patients with rheumatoid arthritis. Author(s): Tanaka S, Tatsumi K, Tomita T, Kimura M, Takano T, Yoshikawa H, Amino N. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 353-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595635&dopt=Abstract
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Novel pathways that regulate tumor necrosis factor-alpha production in rheumatoid arthritis. Author(s): Gracie JA, Leung BP, McInnes IB. Source: Current Opinion in Rheumatology. 2002 May; 14(3): 270-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981325&dopt=Abstract
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Novel plasma-separation dilayer gellan-gellan-sulfate adsorber for direct removal of extra domain A containing fibronectin from the blood of rheumatoid arthritis patients. Author(s): Miyamoto K, Sugihara K, Abe Y, Nobori T, Tokita M, Komai T. Source: International Journal of Biological Macromolecules. 2002 June 18; 30(3-4): 197204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063122&dopt=Abstract
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Novel pro-inflammatory interleukins: potential therapeutic targets in rheumatoid arthritis. Author(s): Bessis N, Boissier MC. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2001 December; 68(6): 477-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808983&dopt=Abstract
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Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile idiopathic arthritis). Author(s): Agle LM, Rosenkranz M, Lehman TJ. Source: Expert Opinion on Investigational Drugs. 2003 January; 12(1): 19-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517251&dopt=Abstract
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Occipitocervical fusion for rheumatoid arthritis using the inside-outside stabilization technique. Author(s): Sandhu FA, Pait TG, Benzel E, Henderson FC. Source: Spine. 2003 February 15; 28(4): 414-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590220&dopt=Abstract
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Occupational therapy for rheumatoid arthritis: a systematic review. Author(s): Steultjens EM, Dekker J, Bouter LM, van Schaardenburg D, van Kuyk MA, van den Ende CH. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 672-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522844&dopt=Abstract
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Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis. Author(s): Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL. Source: The Journal of Rheumatology. 2002 January; 29(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824973&dopt=Abstract
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OMERACT 6 Economics Working Group report: a proposal for a reference case for economic evaluation in rheumatoid arthritis. Author(s): Gabriel S, Drummond M, Maetzel A, Boers M, Coyle D, Welch V, Tugwell P; Patient Perspective Group. Source: The Journal of Rheumatology. 2003 April; 30(4): 886-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672223&dopt=Abstract
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OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. Author(s): Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B, Shnier R, O'Connor P, Klarlund M, Emery P, Genant H, Lassere M, Edmonds J. Source: The Journal of Rheumatology. 2003 June; 30(6): 1385-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784422&dopt=Abstract
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OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 3: an international multicenter reliability study using the RA-MRI Score. Author(s): Lassere M, McQueen F, Ostergaard M, Conaghan P, Shnier R, Peterfy C, Klarlund M, Bird P, O'Connor P, Stewart N, Emery P, Genant H, Edmonds J. Source: The Journal of Rheumatology. 2003 June; 30(6): 1366-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784419&dopt=Abstract
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OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 4: an international multicenter longitudinal study using the RA-MRI Score. Author(s): Conaghan P, Lassere M, Ostergaard M, Peterfy C, McQueen F, O'Connor P, Bird P, Ejbjerg B, Klarlund M, Shnier R, Genant H, Emery P, Edmonds J. Source: The Journal of Rheumatology. 2003 June; 30(6): 1376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784420&dopt=Abstract
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OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 5: an international multicenter reliability study using computerized MRI erosion volume measurements. Author(s): Bird P, Ejbjerg B, McQueen F, Ostergaard M, Lassere M, Edmonds J. Source: The Journal of Rheumatology. 2003 June; 30(6): 1380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784421&dopt=Abstract
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OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Summary of OMERACT 6 MR Imaging Module. Author(s): McQueen F, Lassere M, Edmonds J, Conaghan P, Peterfy C, Bird P, O'Connor P, Ejbjerg B, Klarlund M, Stewart N, Emery P, Shnier R, Genant H, Ostergaard M. Source: The Journal of Rheumatology. 2003 June; 30(6): 1387-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784423&dopt=Abstract
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OMERACT Rheumatoid Arthritis MRI Studies Module. Author(s): Peterfy C, Edmonds J, Lassere M, Conaghan P, Ostergaard M, McQueen F, Genant H, Klarlund M, Ejbjerg B, Stewart N, Bird P, Shnier R, O'Connor P, Emery P. Source: The Journal of Rheumatology. 2003 June; 30(6): 1364-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784418&dopt=Abstract
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OMERACT workshop: repair of structural damage in rheumatoid arthritis. Author(s): Van Der Heijde D, Sharp JT, Rau R, Strand V; Subcommittee on Healing of Erosions of the OMERACT Imaging Committee. Source: The Journal of Rheumatology. 2003 May; 30(5): 1108-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734917&dopt=Abstract
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Onset of rheumatoid arthritis following curative treatment of a somatostatinoma. Author(s): Grasland A, Pouchot J, Vinceneux P, Ruszniewski P. Source: Arthritis and Rheumatism. 2002 January; 46(1): 277-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817604&dopt=Abstract
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Open label study to assess infliximab safety and timing of onset of clinical benefit among patients with rheumatoid arthritis. Author(s): Shergy WJ, Isern RA, Cooley DA, Harshbarger JL, Huffstutter JE, Hughes GM, Spencer-Smith EA, Goldman AL, Roth SH, Toder JS, Warner D, Quinn A, Keenan GF, Schaible TF; PROMPT Study Group. Profiling Remicade Onset with MTX in a Prospective Trial. Source: The Journal of Rheumatology. 2002 April; 29(4): 667-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950005&dopt=Abstract
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Options for blocking interleukin-1 in patients with rheumatoid arthritis. Author(s): Boissier MC, Bessis N, Falgarone G. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 June; 69(4): 351-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184428&dopt=Abstract
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Oral contraceptives, rheumatoid arthritis, and androgens. Author(s): James WH. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 279. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594126&dopt=Abstract
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Orbital myositis in a rheumatoid arthritis patient during etanercept treatment. Author(s): Caramaschi P, Biasi D, Carletto A, Bambara LM. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 136-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673906&dopt=Abstract
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Osteochondral grafting of the metacarpophalangeal joint in rheumatoid arthritis. Author(s): Lo CY, Chang YP. Source: Journal of Hand Surgery (Edinburgh, Lothian). 2003 February; 28(1): 94-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531678&dopt=Abstract
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Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis. Author(s): Hirayama T, Danks L, Sabokbar A, Athanasou NA. Source: Rheumatology (Oxford, England). 2002 November; 41(11): 1232-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421995&dopt=Abstract
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Osteopenia in adults with a history of juvenile rheumatoid arthritis. A population based study. Author(s): French AR, Mason T, Nelson AM, Crowson CS, O'Fallon WM, Khosla S, Gabriel SE. Source: The Journal of Rheumatology. 2002 May; 29(5): 1065-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022324&dopt=Abstract
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Osteoprotegerin expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathies and osteoarthritis and normal controls. Author(s): Haynes DR, Barg E, Crotti TN, Holding C, Weedon H, Atkins GJ, Zannetino A, Ahern MJ, Coleman M, Roberts-Thomson PJ, Kraan M, Tak PP, Smith MD. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 123-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509625&dopt=Abstract
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Osteoprotegerin, an endogenous antiosteoclast factor for protecting bone in rheumatoid arthritis. Author(s): Bolon B, Shalhoub V, Kostenuik PJ, Campagnuolo G, Morony S, Boyle WJ, Zack D, Feige U. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3121-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483715&dopt=Abstract
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Outcome after single technique ankle arthrodesis in patients with rheumatoid arthritis. Author(s): Kennedy JG, Harty JA, Casey K, Jan W, Quinlan WB. Source: Clinical Orthopaedics and Related Research. 2003 July; (412): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838063&dopt=Abstract
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Outcome of penetrating keratoplasty in rheumatoid arthritis. Author(s): Pleyer U, Bertelmann E, Rieck P, Hartmann C. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2002 July-August; 216(4): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207127&dopt=Abstract
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Overexpression of transcripts containing LINE-1 in the synovia of patients with rheumatoid arthritis. Author(s): Ali M, Veale DJ, Reece RJ, Quinn M, Henshaw K, Zanders ED, Markham AF, Emery P, Isaacs JD. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 663-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810431&dopt=Abstract
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p21waf1/cip1 is down-regulated in conjunction with up-regulation of c-Fos in the lymphocytes of rheumatoid arthritis patients. Author(s): Hikasa M, Yamamoto E, Kawasaki H, Komai K, Shiozawa K, Hashiramoto A, Miura Y, Shiozawa S. Source: Biochemical and Biophysical Research Communications. 2003 April 25; 304(1): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705898&dopt=Abstract
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p53 and matrix metalloproteinases in rheumatoid arthritis: tip of an angiogenic iceberg? Author(s): Khan M. Source: Seminars in Arthritis and Rheumatism. 2002 April; 31(5): 287-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11965592&dopt=Abstract
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Palisaded neutrophilic granulomatous dermatitis in rheumatoid arthritis. Author(s): Sangueza OP, Caudell MD, Mengesha YM, Davis LS, Barnes CJ, Griffin JE, Fleischer AB, Jorizzo JL. Source: Journal of the American Academy of Dermatology. 2002 August; 47(2): 251-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140472&dopt=Abstract
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Paraplegia in a patient receiving anti-tumor necrosis factor therapy for rheumatoid arthritis: comment on the article by Mohan et al. Author(s): van der Laken CJ, Lems WF, van Soesbergen RM, van der Sande JJ, Dijkmans BA. Source: Arthritis and Rheumatism. 2003 January; 48(1): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528130&dopt=Abstract
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Parvovirus B19 in the acute arthropathies and juvenile rheumatoid arthritis. Author(s): Oguz F, Akdeniz C, Unuvar E, Kucukbasmaci O, Sidal M. Source: Journal of Paediatrics and Child Health. 2002 August; 38(4): 358-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173996&dopt=Abstract
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Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Author(s): Goldring SR. Source: Rheumatology (Oxford, England). 2003 May; 42 Suppl 2: Ii11-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817090&dopt=Abstract
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Pathogenesis of bone erosions in rheumatoid arthritis. Author(s): Goldring SR. Source: Current Opinion in Rheumatology. 2002 July; 14(4): 406-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118176&dopt=Abstract
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Pathologic thrombopoiesis of rheumatoid arthritis. Author(s): Ertenli I, Kiraz S, Ozturk MA, Haznedaroglu I, Celik I, Calguneri M. Source: Rheumatology International. 2003 March; 23(2): 49-60. Epub 2003 February 11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634936&dopt=Abstract
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Patient compliance in rheumatoid arthritis, polymyalgia rheumatica, and gout. Author(s): de Klerk E, van der Heijde D, Landewe R, van der Tempel H, Urquhart J, van der Linden S. Source: The Journal of Rheumatology. 2003 January; 30(1): 44-54. Erratum In: J Rheumatol. 2003 February; 30(2): 423. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508389&dopt=Abstract
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Patient education for adults with rheumatoid arthritis. Author(s): Riemsma RP, Kirwan JR, Taal E, Rasker JJ. Source: Cochrane Database Syst Rev. 2003; (2): Cd003688. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804484&dopt=Abstract
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Patient education programmes for adults with rheumatoid arthritis. Author(s): Riemsma RP, Taal E, Kirwan JR, Rasker JJ. Source: Bmj (Clinical Research Ed.). 2002 September 14; 325(7364): 558-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228119&dopt=Abstract
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Patients' views of priority setting for new medicines. A qualitative study of patients with rheumatoid arthritis. Author(s): Lindblad AK, Hartzema AG, Jansson L, Feltelius N. Source: Scandinavian Journal of Rheumatology. 2002; 31(6): 324-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492246&dopt=Abstract
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Pattern of humoral reactivity to type II collagen in rheumatoid arthritis. Author(s): Boissier MC, Chiocchia G, Texier B, Fournier C. Source: Clinical and Experimental Immunology. 1989 November; 78(2): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412745&dopt=Abstract
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Patterns of disease modifying antirheumatic drug use in a Spanish cohort of patients with rheumatoid arthritis. Author(s): Gonzalez-Alvaro I, Carmona L, Balsa A, Sanmarti R, Belmonte MA, Tena X; EMECAR Study Group. Source: The Journal of Rheumatology. 2003 April; 30(4): 697-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672186&dopt=Abstract
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Perceptions of control in patients with rheumatoid arthritis. Author(s): Ryan S, Hassell A, Dawes P, Kendall S. Source: Nurs Times. 2003 April 1-7; 99(13): 36-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715557&dopt=Abstract
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Perinatal characteristics and risk of rheumatoid arthritis. Author(s): Jacobsson LT, Jacobsson ME, Askling J, Knowler WC. Source: Bmj (Clinical Research Ed.). 2003 May 17; 326(7398): 1068-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750209&dopt=Abstract
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Peripheral-type benzodiazepine receptors in human mononuclear cells of patients affected by osteoarthritis, rheumatoid arthritis or psoriasic arthritis. Author(s): Bazzichi L, Betti L, Giannaccini G, Rossi A, Lucacchini A. Source: Clinical Biochemistry. 2003 February; 36(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554061&dopt=Abstract
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Peritoneal tuberculosis mimicking advanced ovarian cancer in a patient treated with methotrexate for chronic rheumatoid arthritis. Author(s): Huesler M, Ruef C, Pfyffer GE, Haller U, Fink D. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 May; 23(3): 315-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850870&dopt=Abstract
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Pharmacological management of early rheumatoid arthritis--does combination therapy improve outcomes? Author(s): Dougados M, Smolen JS. Source: J Rheumatol Suppl. 2002 November; 66: 20-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435165&dopt=Abstract
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Physiotherapy in subtropic climate improves functional capacity and health-related quality of life in Swedish patients with rheumatoid arthritis and spondylarthropathies still after 6 months. Author(s): Hafstrom I, Hallengren M. Source: Scandinavian Journal of Rheumatology. 2003; 32(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737330&dopt=Abstract
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Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid arthritis. Author(s): Pillemer S, Gulko P, Ligier S, Yarboro C, Gourley M, Goldbach-Mansky R, Siegel R, Hirsch R, Pucino F, Tilley B, Wilder RL. Source: The Journal of Rheumatology. 2003 January; 30(1): 41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508388&dopt=Abstract
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Plasma pyridoxal 5'-phosphate concentration is correlated with functional vitamin B-6 indices in patients with rheumatoid arthritis and marginal vitamin B-6 status. Author(s): Chiang EP, Bagley PJ, Roubenoff R, Nadeau M, Selhub J. Source: The Journal of Nutrition. 2003 April; 133(4): 1056-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672918&dopt=Abstract
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Platelet function is inhibited by non-selective non-steroidal anti-inflammatory drugs but not by cyclo-oxygenase-2-selective inhibitors in patients with rheumatoid arthritis. Author(s): Knijff-Dutmer EA, Kalsbeek-Batenburg EM, Koerts J, van de Laar MA. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 458-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961179&dopt=Abstract
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Polymorphism at position -308 of the tumor necrosis factor alpha gene influences outcome of infliximab therapy in rheumatoid arthritis. Author(s): Mugnier B, Balandraud N, Darque A, Roudier C, Roudier J, Reviron D. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1849-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847678&dopt=Abstract
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Polymorphism in the immunoglobulin VH gene V1-69 affects susceptibility to rheumatoid arthritis in subjects lacking the HLA-DRB1 shared epitope. Author(s): Vencovsky J, Zd'arsky E, Moyes SP, Hajeer A, Ruzickova S, Cimburek Z, Ollier WE, Maini RN, Mageed RA. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 401-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961170&dopt=Abstract
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Polymorphism in the matrix metalloproteinase-1 promoter gene and severity of rheumatoid arthritis. Author(s): Massarotti M, Marchesoni A, Biondi ML, Marasini B. Source: The Journal of Rheumatology. 2002 October; 29(10): 2241; Author Reply 2242. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375344&dopt=Abstract
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Polymorphism in the stromelysin 1 (matrix metalloproteinase 3) promoter gene and severity of rheumatoid arthritis: comment on the article by Constantin et al. Author(s): Massarotti M, Marasini B, Marchesoni A, Arreghini M, Biondi ML. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2695-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130493&dopt=Abstract
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Polymyalgia rheumatica and elderly-onset rheumatoid arthritis. Author(s): Shiozawa S. Source: Intern Med. 2002 August; 41(8): 605. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211524&dopt=Abstract
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Polyreactivity of human IgG Fc-binding phage antibodies constructed from synovial fluid CD38+ B cells of patients with rheumatoid arthritis. Author(s): van Esch WJ, Reparon-Schuijt CC, Hamstra HJ, van Kooten C, Logtenberg T, Breedveld FC, Verweij CL. Source: Journal of Autoimmunity. 2002 December; 19(4): 241-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473245&dopt=Abstract
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Population pharmacokinetic analysis of meloxicam in rheumatoid arthritis patients. Author(s): Meineke I, Turck D. Source: British Journal of Clinical Pharmacology. 2003 January; 55(1): 32-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534638&dopt=Abstract
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Possible role of shared epitope status in the relationship between matrix metalloproteinase 3 genotype and radiographic progression of rheumatoid arthritis: comment on the article by Constantin et al. Author(s): de Vries N, Tak PP. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1162-3; Author Reply 1163-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687566&dopt=Abstract
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Posterior atlanto-axial fusion with the Olerud Cervical Fixation System for odontoid fractures and C1-C2 instability in rheumatoid arthritis. Author(s): Cornefjord M, Henriques T, Alemany M, Olerud C. Source: European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 2003 February; 12(1): 91-6. Epub 2002 October 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592552&dopt=Abstract
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Posterior tibial tendon dysfunction and MR imaging in rheumatoid arthritis. Author(s): Hasler P, Hintermann B, Meier M. Source: Rheumatology International. 2002 May; 22(1): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120910&dopt=Abstract
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Post-processing water-fat imaging technique for fat suppression in a low-field MR imaging system, evaluation in patients with rheumatoid arthritis. Author(s): Palosaari K, Tervonen O. Source: Magma (New York, N.Y.). 2002 November; 15(1-3): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413559&dopt=Abstract
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Power Doppler sonography in the assessment of synovial tissue of the knee joint in rheumatoid arthritis: a preliminary experience. Author(s): Carotti M, Salaffi F, Manganelli P, Salera D, Simonetti B, Grassi W. Source: Annals of the Rheumatic Diseases. 2002 October; 61(10): 877-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228155&dopt=Abstract
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Predicting mortality in patients with rheumatoid arthritis. Author(s): Wolfe F, Michaud K, Gefeller O, Choi HK. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1530-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794820&dopt=Abstract
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Predictors of improvement in a cognitive-behavioral intervention for women with rheumatoid arthritis. Author(s): Sinclair VG, Wallston KA. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2001 Fall; 23(4): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11761346&dopt=Abstract
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Predictors of infection in rheumatoid arthritis. Author(s): Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2294-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355476&dopt=Abstract
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Predictors of radiological progression and changes in hand bone density in early rheumatoid arthritis. Author(s): Berglin E, Lorentzon R, Nordmark L, Nilsson-Sojka B, Rantapaa Dahlqvist S. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 268-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595621&dopt=Abstract
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Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis. Author(s): Zou J, Zhang Y, Thiel A, Rudwaleit M, Shi SL, Radbruch A, Poole R, Braun J, Sieper J. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 846-55. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730543&dopt=Abstract
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Preferences for improved health examined in 1,024 patients with rheumatoid arthritis: pain has highest priority. Author(s): Heiberg T, Kvien TK. Source: Arthritis and Rheumatism. 2002 Aug15; 47(4): 391-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209485&dopt=Abstract
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Pregnancy and oral contraceptive use do not significantly influence outcome in long term rheumatoid arthritis. Author(s): Drossaers-Bakker KW, Zwinderman AH, van Zeben D, Breedveld FC, Hazes JM. Source: Annals of the Rheumatic Diseases. 2002 May; 61(5): 405-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959763&dopt=Abstract
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Preliminary guidelines for diagnosing and treating tuberculosis in patients with rheumatoid arthritis in immunosuppressive trials or being treated with biological agents. Author(s): Furst DE, Cush J, Kaufmann S, Siegel J, Kurth R. Source: Annals of the Rheumatic Diseases. 2002 November; 61 Suppl 2: Ii62-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379625&dopt=Abstract
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Presence of a 88 kDa Eales protein in uveitis, tuberculosis, leprosy and rheumatoid arthritis. Author(s): Rajesh M, Sulochana KN, Sundaram AL, Krishnakumar S, Biswas J, Ramakrishnan S. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 February; 9(2): Cr95-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601295&dopt=Abstract
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Presence of autoantibodies to the glycolytic enzyme alpha-enolase in sera from patients with early rheumatoid arthritis. Author(s): Saulot V, Vittecoq O, Charlionet R, Fardellone P, Lange C, Marvin L, Machour N, Le Loet X, Gilbert D, Tron F. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1196-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115223&dopt=Abstract
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Pretreatment cytokine profiles of peripheral blood mononuclear cells and serum from patients with rheumatoid arthritis in different american college of rheumatology response groups to methotrexate. Author(s): Seitz M, Zwicker M, Villiger PM. Source: The Journal of Rheumatology. 2003 January; 30(1): 28-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508386&dopt=Abstract
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Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis? Author(s): Salvador G, Gomez A, Vinas O, Ercilla G, Canete JD, Munoz-Gomez J, Sanmarti R. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 972-5. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730510&dopt=Abstract
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Prevalence of C282Y mutation in patients with rheumatoid arthritis and spondylarthritis. Author(s): Rovetta G, Grignolo MC, Buffrini L, Monteforte P. Source: Int J Tissue React. 2002; 24(3): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635863&dopt=Abstract
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Prevalence of dermatophytosis in patients with rheumatoid arthritis. Author(s): Bicer A, Tursen U, Cimen OB, Kaya TI, Ozisik S, Ikizoglu G, Erdogan C. Source: Rheumatology International. 2003 January; 23(1): 37-40. Epub 2002 August 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548440&dopt=Abstract
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Prevalence of rheumatoid arthritis and hepatitis C in those age 60 and older in a US population based study. Author(s): Hsu FC, Starkebaum G, Boyko EJ, Dominitz JA. Source: The Journal of Rheumatology. 2003 March; 30(3): 455-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610800&dopt=Abstract
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Prevalence of rheumatoid arthritis in persons 60 years of age and older in the United States: effect of different methods of case classification. Author(s): Rasch EK, Hirsch R, Paulose-Ram R, Hochberg MC. Source: Arthritis and Rheumatism. 2003 April; 48(4): 917-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687533&dopt=Abstract
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Prevalence of rheumatoid arthritis. Author(s): Zauli D, Zucchini S, Manfredini E, Grassi A, Ballardini G, Fusconi M, Bianchi FB. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 696-7; Author Reply 697. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709551&dopt=Abstract
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Prevalence of secondary amyloidosis in Asian North Indian patients with rheumatoid arthritis. Author(s): Wakhlu A, Krisnani N, Hissaria P, Aggarwal A, Misra R. Source: The Journal of Rheumatology. 2003 May; 30(5): 948-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734887&dopt=Abstract
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Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis. Author(s): de Nijs RN, Jacobs JW, Bijlsma JW, Lems WF, Laan RF, Houben HH, ter Borg EJ, Huisman AM, Bruyn GA, van Oijen PL, Westgeest AA, Algra A, Hofman DM; Osteoporosis Working Group, Dutch Society for Rheumaology. Source: Rheumatology (Oxford, England). 2001 December; 40(12): 1375-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752508&dopt=Abstract
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Prevention of nonadherence to nonsteroidal anti-inflammatory medications for newly diagnosed patients with juvenile rheumatoid arthritis. Author(s): Rapoff MA, Belmont J, Lindsley C, Olson N, Morris J, Padur J. Source: Health Psychology : Official Journal of the Division of Health Psychology, American Psychological Association. 2002 November; 21(6): 620-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433016&dopt=Abstract
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Prevention or retardation of joint damage in rheumatoid arthritis: issues of definition, evaluation and interpretation of plain radiographs. Author(s): Boers M, van der Heijde DM. Source: Drugs. 2002; 62(12): 1717-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149042&dopt=Abstract
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Prognostic factors in juvenile rheumatoid arthritis: a case-control study revealing early predictors and outcome after 14.9 years. Author(s): Flato B, Lien G, Smerdel A, Vinje O, Dale K, Johnston V, Sorskaar D, Moum T, Ploski R, Forre O. Source: The Journal of Rheumatology. 2003 February; 30(2): 386-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563700&dopt=Abstract
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Prospective analysis of the impact of HLA-DR and -DQ on joint destruction in recentonset rheumatoid arthritis. Author(s): Wagner U, Kaltenhauser S, Pierer M, Seidel W, Troltzsch M, Hantzschel H, Kalden JR, Wassmuth R. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 553-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649403&dopt=Abstract
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Protein kinase signals activate interleukin 16 encoding transcripts in rheumatoid arthritis versus osteoarthritis synovial fibroblasts. Author(s): Schuler MK, Sell S, Aicher WK. Source: Annals of the Rheumatic Diseases. 2003 February; 62(2): 182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525392&dopt=Abstract
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Purine enzymes in patients with rheumatoid arthritis treated with methotrexate. Author(s): van Ede AE, Laan RF, De Abreu RA, Stegeman AB, van de Putte LB. Source: Annals of the Rheumatic Diseases. 2002 December; 61(12): 1060-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429535&dopt=Abstract
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QT dispersion and cardiac involvement in patients with rheumatoid arthritis. Author(s): Cindas A, Gokce-Kutsal Y, Tokgozoglu L, Karanfil A. Source: Scandinavian Journal of Rheumatology. 2002; 31(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922196&dopt=Abstract
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Quality of life, social support, and knowledge of disease in women with rheumatoid arthritis. Author(s): Minnock P, Fitzgerald O, Bresnihan B. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687514&dopt=Abstract
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Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases. Author(s): Stolt P, Bengtsson C, Nordmark B, Lindblad S, Lundberg I, Klareskog L, Alfredsson L; EIRA study group. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 835-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922955&dopt=Abstract
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Radiographic changes after resection of the distal ulna in patients with rheumatoid arthritis. Author(s): Masada K, Hashimoto H, Yasuda M. Source: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery / Nordisk Plastikkirurgisk Forening [and] Nordisk Klubb for Handkirurgi. 2002; 36(5): 300-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477089&dopt=Abstract
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Radiographic damage associated with low bone mineral density and vertebral deformities in rheumatoid arthritis: the Oslo-Truro-Amsterdam (OSTRA) collaborative study. Author(s): Lodder MC, Haugeberg G, Lems WF, Uhlig T, Orstavik RE, Kostense PJ, Dijkmans BA, Kvien TK, Woolf AD; Oslo-Truro-Amsterdam (OSTRA) Collaborative Study. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687512&dopt=Abstract
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Radiographic data from recent randomized controlled trials in rheumatoid arthritis: what have we learned? Author(s): Strand V, Sharp JT. Source: Arthritis and Rheumatism. 2003 January; 48(1): 21-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528100&dopt=Abstract
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Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis. Author(s): Forsblad D'Elia H, Larsen A, Waltbrand E, Kvist G, Mellstrom D, Saxne T, Ohlsson C, Nordborg E, Carlsten H. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 617-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810422&dopt=Abstract
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Radiologic findings of the lumbar spine in patients with rheumatoid arthritis, and a review of pathologic mechanisms. Author(s): Kawaguchi Y, Matsuno H, Kanamori M, Ishihara H, Ohmori K, Kimura T. Source: Journal of Spinal Disorders & Techniques. 2003 February; 16(1): 38-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571483&dopt=Abstract
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Radiologic outcome and its relationship to functional disability in juvenile rheumatoid arthritis. Author(s): Oen K, Reed M, Malleson PN, Cabral DA, Petty RE, Rosenberg AM, Cheang M. Source: The Journal of Rheumatology. 2003 April; 30(4): 832-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672208&dopt=Abstract
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Rate of death due to leukemia/lymphoma in patients with rheumatoid arthritis. Author(s): Wolfe F, Fries JF. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2694-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130492&dopt=Abstract
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Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Author(s): Crotti TN, Smith MD, Weedon H, Ahern MJ, Findlay DM, Kraan M, Tak PP, Haynes DR. Source: Annals of the Rheumatic Diseases. 2002 December; 61(12): 1047-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429533&dopt=Abstract
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Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Author(s): Wong M, Toh L, Wilson A, Rowley K, Karschimkus C, Prior D, Romas E, Clemens L, Dragicevic G, Harianto H, Wicks I, McColl G, Best J, Jenkins A. Source: Arthritis and Rheumatism. 2003 January; 48(1): 81-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528107&dopt=Abstract
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Reduced bone mineral density in men with rheumatoid arthritis: comment on the article by Haugeberg et al. Author(s): Nolla JM, Mateo L. Source: Arthritis and Rheumatism. 2001 December; 44(12): 2941-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762960&dopt=Abstract
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Reduced chemokine and matrix metalloproteinase expression in patients with rheumatoid arthritis achieving remission. Author(s): Katrib A, Smith MD, Ahern MJ, Slavotinek J, Stafford L, Cuello C, Bertouch JV, McNeil HP, Youssef PP. Source: The Journal of Rheumatology. 2003 January; 30(1): 10-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508384&dopt=Abstract
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Reduction in plasma homocysteine level in patients with rheumatoid arthritis given pulsed glucocorticoid treatment. Author(s): Lazzerini PE, Capecchi PL, Bisogno S, Galeazzi M, Marcolongo R, Pasini FL. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 694-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810448&dopt=Abstract
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Regional analysis of p53 mutations in rheumatoid arthritis synovium. Author(s): Yamanishi Y, Boyle DL, Rosengren S, Green DR, Zvaifler NJ, Firestein GS. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 July 23; 99(15): 10025-30. Epub 2002 Jul 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119414&dopt=Abstract
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Regression of subacute cutaneous lupus erythematosus in a patient with rheumatoid arthritis treated with a biologic tumor necrosis factor alpha-blocking agent: comment on the article by Pisetsky and the letter from Aringer et al. Author(s): Fautrel B, Foltz V, Frances C, Bourgeois P, Rozenberg S. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1408-9; Author Reply 1409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115253&dopt=Abstract
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Regulation of CCR5 expression and MIP-1alpha production in CD4+ T cells from patients with rheumatoid arthritis. Author(s): Wang CR, Liu MF. Source: Clinical and Experimental Immunology. 2003 May; 132(2): 371-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699431&dopt=Abstract
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Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes. Author(s): Sen M, Reifert J, Lauterbach K, Wolf V, Rubin JS, Corr M, Carson DA. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2867-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428226&dopt=Abstract
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Relapse of rheumatoid arthritis after substitution of oral for parenteral administration of methotrexate. Author(s): Rozin A, Schapira D, Balbir-Gurman A, Braun-Moscovici Y, Markovits D, Militianu D, Nahir MA. Source: Annals of the Rheumatic Diseases. 2002 August; 61(8): 756-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117691&dopt=Abstract
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Relationship of social role quality to psychological well-being in women with rheumatoid arthritis. Author(s): Plach SK, Heidrich SM, Waite RM. Source: Research in Nursing & Health. 2003 June; 26(3): 190-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754727&dopt=Abstract
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Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis. Author(s): Friese MA, Manuelian T, Junnikkala S, Hellwage J, Meri S, Peter HH, Gordon DL, Eibel H, Zipfel PF. Source: Clinical and Experimental Immunology. 2003 June; 132(3): 485-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12780697&dopt=Abstract
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Remission of lymphoma after drug withdrawal in rheumatoid arthritis. Author(s): Lim IG, Bertouch JV. Source: The Medical Journal of Australia. 2002 November 4; 177(9): 500-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405893&dopt=Abstract
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Repair of erosions in rheumatoid arthritis does occur. Results from 2 studies by the OMERACT Subcommittee on Healing of Erosions. Author(s): Sharp JT, Van Der Heijde D, Boers M, Boonen A, Bruynesteyn K, Emery P, Genant HK, Herborn G, Jurik A, Lassere M, McQueen F, Ostergaard M, Peterfy C, Rau R, Strand V, Wassenberg S, Weissman B; Subcommittee on Healing of Erosions of the OMERACT Imaging Committee. Source: The Journal of Rheumatology. 2003 May; 30(5): 1102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734916&dopt=Abstract
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Response to etanercept (Enbrel) in elderly patients with rheumatoid arthritis: a retrospective analysis of clinical trial results. Author(s): Fleischmann RM, Baumgartner SW, Tindall EA, Weaver AL, Moreland LW, Schiff MH, Martin RW, Spencer-Green GT. Source: The Journal of Rheumatology. 2003 April; 30(4): 691-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672185&dopt=Abstract
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Responsiveness of health status measures and utility-based methods in patients with rheumatoid arthritis. Author(s): Salaffi F, Stancati A, Carotti M. Source: Clinical Rheumatology. 2002 November; 21(6): 478-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447631&dopt=Abstract
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Reumacon (CPH82) showed similar x-ray progression and clinical effects as methotrexate in a two year comparative study on patients with early rheumatoid arthritis. Author(s): Svensson B, Pettersson H. Source: Scandinavian Journal of Rheumatology. 2003; 32(2): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737326&dopt=Abstract
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Rheumatoid arthritis and angiogenesis. Author(s): Yamanaka H. Source: Intern Med. 2003 March; 42(3): 297-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705803&dopt=Abstract
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Rheumatoid arthritis and immune thrombocytopenia: a report of two cases. Author(s): Ustun C, Kallab A, Loebl D, Jillela A, Majewski B, Mazzella F, Burgess R. Source: Clinical Rheumatology. 2002 November; 21(6): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447648&dopt=Abstract
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Rheumatoid arthritis and macrovascular disease. Author(s): Alkaabi JK, Ho M, Levison R, Pullar T, Belch JJ. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595625&dopt=Abstract
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Rheumatoid arthritis and the Arava (leflunomide) controversy. Author(s): Turkoski BB. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2003 January-February; 22(1): 48-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640952&dopt=Abstract
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Rheumatoid arthritis associated with ulcerative colitis. Author(s): Mosquera-Martinez JA. Source: Annals of the Rheumatic Diseases. 2001 December; 60(12): 1155. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11760722&dopt=Abstract
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Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity. Author(s): Carmona L, Gonzalez-Alvaro I, Balsa A, Angel Belmonte M, Tena X, Sanmarti R. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 897-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922967&dopt=Abstract
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Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activation of the STAT-1 pathway between rheumatoid tissues. Author(s): van der Pouw Kraan TC, van Gaalen FA, Kasperkovitz PV, Verbeet NL, Smeets TJ, Kraan MC, Fero M, Tak PP, Huizinga TW, Pieterman E, Breedveld FC, Alizadeh AA, Verweij CL. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2132-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905466&dopt=Abstract
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Rheumatoid arthritis of the cervical spine. Author(s): Kolen ER, Schmidt MH. Source: Seminars in Neurology. 2002 June; 22(2): 179-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524563&dopt=Abstract
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Rheumatoid arthritis of the shoulder. Author(s): Chen AL, Joseph TN, Zuckerman JD. Source: J Am Acad Orthop Surg. 2003 January-February; 11(1): 12-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699368&dopt=Abstract
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Rheumatoid arthritis presenting as an invasive soft-tissue tumour. Author(s): Moran M, Fang C, Paul A. Source: Archives of Orthopaedic and Trauma Surgery. 2002 December; 122(9-10): 538-40. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483339&dopt=Abstract
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Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse populations. Author(s): MacKay K, Milicic A, Lee D, Tikly M, Laval S, Shatford J, Wordsworth P. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509628&dopt=Abstract
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Rheumatoid arthritis synoviocyte survival is dependent on Stat3. Author(s): Krause A, Scaletta N, Ji JD, Ivashkiv LB. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 December 1; 169(11): 66106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444174&dopt=Abstract
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Rheumatoid arthritis, methotrexate, and lymphoma: risk substitution, or cat and mouse with Epstein-Barr virus? Author(s): Starkebaum G. Source: The Journal of Rheumatology. 2001 December; 28(12): 2573-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764198&dopt=Abstract
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Rheumatoid arthritis. Author(s): Dedhia HV, DiBartolomeo A. Source: Critical Care Clinics. 2002 October; 18(4): 841-54, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422843&dopt=Abstract
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Rheumatoid arthritis. Current therapy for a highly treatable disease. Author(s): Sherman JA. Source: Adv Nurse Pract. 2001 December; 9(12): 28-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400351&dopt=Abstract
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Rheumatoid arthritis: an ancient disease or a new one? Author(s): Leden I. Source: Arthritis and Rheumatism. 2001 December; 45(6): 538. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762689&dopt=Abstract
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Rheumatoid arthritis: principles of early treatment. Author(s): Bresnihan B. Source: J Rheumatol Suppl. 2002 November; 66: 9-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435163&dopt=Abstract
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Rheumatoid factor is the strongest predictor of radiological progression of rheumatoid arthritis in a three-year prospective study in community-recruited patients. Author(s): Vittecoq O, Pouplin S, Krzanowska K, Jouen-Beades F, Menard JF, Gayet A, Daragon A, Tron F, Le Loet X. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 939-46. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730503&dopt=Abstract
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Rheumatoid neutrophilic dermatitis, rheumatoid papules, and rheumatoid nodules in a patient with seronegative rheumatoid arthritis. Author(s): Yamamoto T, Matsunaga T, Nishioka K. Source: Journal of the American Academy of Dermatology. 2003 April; 48(4): 634-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664038&dopt=Abstract
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Rheumatologists' opinions on the feasibility of a measurement feedback system in rheumatoid arthritis and the influence of motivation. Author(s): Fransen J, Daneel S, Langenegger T, Michel BA; Swiss Clinical Quality Management in rheumatoid arthritis. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 924-8. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730552&dopt=Abstract
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Risk communication in rheumatoid arthritis. Author(s): Fraenkel L, Bogardus S, Concato J, Felson D. Source: The Journal of Rheumatology. 2003 March; 30(3): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610798&dopt=Abstract
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Risk of malignant lymphomas in patients with rheumatoid arthritis and in their firstdegree relatives. Author(s): Ekstrom K, Hjalgrim H, Brandt L, Baecklund E, Klareskog L, Ekbom A, Askling J. Source: Arthritis and Rheumatism. 2003 April; 48(4): 963-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687538&dopt=Abstract
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Role of Crk-associated substrate lymphocyte type in the pathophysiology of rheumatoid arthritis in tax transgenic mice and in humans. Author(s): Miyake-Nishijima R, Iwata S, Saijo S, Kobayashi H, Kobayashi S, SoutaKuribara A, Hosono O, Kawasaki H, Tanaka H, Ikeda E, Okada Y, Iwakura Y, Morimoto C. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1890-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847683&dopt=Abstract
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Role of Fcgamma receptors IIA, IIIA, and IIIB in susceptibility to rheumatoid arthritis. Author(s): Radstake TR, Petit E, Pierlot C, van de Putte LB, Cornelis F, Barrera P. Source: The Journal of Rheumatology. 2003 May; 30(5): 926-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734884&dopt=Abstract
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Role of human leukocyte antigen DRB1*0307 and DRB1*0308 in susceptibility to juvenile rheumatoid arthritis. Author(s): Alsaeid KM, Haider MZ, al-Awadhi AM, Srivastva BS, Ayoub EM. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 399-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846065&dopt=Abstract
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Role of macrophage inflammatory protein-3alpha and its ligand CCR6 in rheumatoid arthritis. Author(s): Ruth JH, Shahrara S, Park CC, Morel JC, Kumar P, Qin S, Koch AE. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 April; 83(4): 579-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695561&dopt=Abstract
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Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis. Author(s): Tan AL, Tanner SF, Conaghan PG, Radjenovic A, O'Connor P, Brown AK, Emery P, McGonagle D. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1214-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746894&dopt=Abstract
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Safety and efficacy of disease-modifying antirheumatic agents in rheumatoid arthritis and juvenile rheumatoid arthritis. Author(s): Fleischmann R. Source: Expert Opinion on Drug Safety. 2003 July; 2(4): 347-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904092&dopt=Abstract
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Salmonella septicemia in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: association with decreased interferon-gamma production and Toll-like receptor 4 expression. Author(s): Netea MG, Radstake T, Joosten LA, van der Meer JW, Barrera P, Kullberg BJ. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1853-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847679&dopt=Abstract
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Scintigraphic detection of tumour necrosis factor in patients with rheumatoid arthritis. Author(s): Barrera P, Oyen WJ, Boerman OC, van Riel PL. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 825-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922953&dopt=Abstract
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Screening for extensor tendon rupture in rheumatoid arthritis. Author(s): Williamson L, Burge P. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 810. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771447&dopt=Abstract
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Screening the genome for rheumatoid arthritis susceptibility genes: a replication study and combined analysis of 512 multicase families. Author(s): Jawaheer D, Seldin MF, Amos CI, Chen WV, Shigeta R, Etzel C, Damle A, Xiao X, Chen D, Lum RF, Monteiro J, Kern M, Criswell LA, Albani S, Nelson JL, Clegg DO, Pope R, Schroeder HW Jr, Bridges SL Jr, Pisetsky DS, Ward R, Kastner DL, Wilder RL, Pincus T, Callahan LF, Flemming D, Wener MH, Gregersen PK; North American Rheumatoid Arthritis Consortium. Source: Arthritis and Rheumatism. 2003 April; 48(4): 906-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687532&dopt=Abstract
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Seasonal distribution of relapse onset in rheumatoid arthritis and spondyloarthropathy: the possible effect of the solar factor. Author(s): Rozin A, Balbir-Gurman A, Schapira D. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 161-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747269&dopt=Abstract
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Selective elimination of synovial inflammatory macrophages in rheumatoid arthritis by an Fcgamma receptor I-directed immunotoxin. Author(s): van Roon JA, van Vuuren AJ, Wijngaarden S, Jacobs KM, Bijlsma JW, Lafeber FP, Thepen T, van de Winkel JG. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1229-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746896&dopt=Abstract
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Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. Author(s): Kontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1551-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794822&dopt=Abstract
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Serious bacterial infections in patients with rheumatoid arthritis under anti-TNFalpha therapy. Author(s): Kroesen S, Widmer AF, Tyndall A, Hasler P. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 617-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709536&dopt=Abstract
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Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Author(s): Cambridge G, Leandro MJ, Edwards JC, Ehrenstein MR, Salden M, BodmanSmith M, Webster AD. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2146-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905467&dopt=Abstract
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Seropositive rheumatoid arthritis associated with Crohn's disease. Author(s): Georgiadis AN, Tzambouras N, Ioachim E, Tsianos EV, Agnantis N, Drosos AA. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 363-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846059&dopt=Abstract
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Serum levels of cartilage oligomeric matrix protein. A predicting factor and a valuable parameter for disease management in rheumatoid arthritis. Author(s): Skoumal M, Kolarz G, Klingler A. Source: Scandinavian Journal of Rheumatology. 2003; 32(3): 156-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892252&dopt=Abstract
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Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones. Author(s): Vogl D, Falk W, Dorner M, Scholmerich J, Straub RH. Source: The Journal of Rheumatology. 2003 February; 30(2): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563679&dopt=Abstract
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Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis. Author(s): Green MJ, Gough AK, Devlin J, Smith J, Astin P, Taylor D, Emery P. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509618&dopt=Abstract
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Serum paraoxonase activity decreases in rheumatoid arthritis. Author(s): Tanimoto N, Kumon Y, Suehiro T, Ohkubo S, Ikeda Y, Nishiya K, Hashimoto K. Source: Life Sciences. 2003 May 9; 72(25): 2877-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697270&dopt=Abstract
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sE-selectin for stratifying outcome in rheumatoid arthritis. Author(s): Egerer K, Hertzer J, Feist E, Albrecht A, Rudolph PE, Dorner T, Burmester GR. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 546-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910562&dopt=Abstract
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Severe Parkinson's disease in rheumatoid arthritis patient treated with infliximab. Author(s): Hrycaj P, Korczowska I, Lacki JK. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 702-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709557&dopt=Abstract
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Sex hormones and rheumatoid arthritis. Author(s): Cutolo M, Villaggio B, Craviotto C, Pizzorni C, Seriolo B, Sulli A. Source: Autoimmunity Reviews. 2002 October; 1(5): 284-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848982&dopt=Abstract
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Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Author(s): Gotzsche PC, Johansen HK. Source: Cochrane Database Syst Rev. 2003; (1): Cd000189. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535392&dopt=Abstract
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Should infection still be considered as the most likely triggering factor for rheumatoid arthritis? Author(s): Carty SM, Snowden N, Silman AJ. Source: The Journal of Rheumatology. 2003 March; 30(3): 425-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610794&dopt=Abstract
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Should rheumatoid arthritis be treated conservatively or aggressively? Author(s): Breedveld FC. Source: Rheumatology (Oxford, England). 2003 May; 42 Suppl 2: Ii41-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817095&dopt=Abstract
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Shoulder joint involvement in patients with newly diagnosed rheumatoid arthritis. Prevalence and associations. Author(s): Olofsson Y, Book C, Jacobsson LT. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 25-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635942&dopt=Abstract
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Silica-related rheumatoid arthritis without lung involvement. Author(s): Markovits D, Schapira D, Wiener A, Nahir AM. Source: Clinical Rheumatology. 2003 February; 22(1): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605320&dopt=Abstract
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Simultaneous occurrence of type I diabetes mellitus and juvenile rheumatoid arthritis. Author(s): Agrawal S, Desai MP. Source: Indian Pediatrics. 2003 June; 40(6): 568-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824669&dopt=Abstract
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Simultaneous, clonally identical T cell expansion in tonsil and synovium in a patient with rheumatoid arthritis and chronic tonsillitis. Author(s): Kawano M, Okada K, Muramoto H, Morishita H, Omura T, Inoue R, Kitajima S, Katano K, Koni I, Mabuchi H, Yachie A. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2483-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130467&dopt=Abstract
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Smoking-gender interaction and risk for rheumatoid arthritis. Author(s): Krishnan E, Sokka T, Hannonen P. Source: Arthritis Research & Therapy. 2003; 5(3): R158-62. Epub 2003 March 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723987&dopt=Abstract
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Solar light effects on onset/relapses and circannual/circadian symptomatology in rheumatoid arthritis. Author(s): Cutolo M. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 148-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747267&dopt=Abstract
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Somatostatin analogs in rheumatoid arthritis and other inflammatory and immunemediated conditions. Author(s): Paran D, Paran H. Source: Curr Opin Investig Drugs. 2003 May; 4(5): 578-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833652&dopt=Abstract
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Splints/orthoses in the treatment of rheumatoid arthritis. Author(s): Egan M, Brosseau L, Farmer M, Ouimet MA, Rees S, Wells G, Tugwell P. Source: Cochrane Database Syst Rev. 2003; (1): Cd004018. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535502&dopt=Abstract
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Sterile corneal melting and necrotizing scleritis after cataract surgery in patients with rheumatoid arthritis and collagen vascular disease. Author(s): Perez VL, Azar DT, Foster CS. Source: Semin Ophthalmol. 2002 September-December; 17(3-4): 124-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759840&dopt=Abstract
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Steroid myopathy in a child with juvenile rheumatoid arthritis. Case report. Author(s): Genel F, Arslanoglu S, Hizarcioglu M, Durmaz B, Uran N, Aktas S. Source: Panminerva Medica. 2003 March; 45(1): 75-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682624&dopt=Abstract
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Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis. Author(s): Groh V, Bruhl A, El-Gabalawy H, Nelson JL, Spies T. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 5; 100(16): 9452-7. Epub 2003 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878725&dopt=Abstract
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Stromal cell-derived factor-1 alpha in rheumatoid arthritis. Author(s): Mittal GA, Joshi VR, Deshpande A. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 915-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826719&dopt=Abstract
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Strong LFA-1 and VCAM-1 expression in histological type II of rheumatoid arthritis. Author(s): Ilgner S, Stiehl P. Source: Cell Mol Biol (Noisy-Le-Grand). 2002; 48 Online Pub: Ol243-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643440&dopt=Abstract
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Subacromial bursitis with rice bodies as the presenting manifestation of rheumatoid arthritis. Author(s): Kataria RK, Chaiamnuay S, Jacobson LD, Brent LH. Source: The Journal of Rheumatology. 2003 June; 30(6): 1354-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784416&dopt=Abstract
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Subcutaneous administration of polymerized-type I collagen for the treatment of patients with rheumatoid arthritis. An open-label pilot trial. Author(s): Furuzawa-Carballeda J, Cabral AR, Zapata-Zuniga M, Alcocer-Varela J. Source: The Journal of Rheumatology. 2003 February; 30(2): 256-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563677&dopt=Abstract
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Subcutaneous, intramuscular, and intraosseous synovial cyst formation around the knee in rheumatoid arthritis/systemic lupus erythematosus overlap syndrome. Author(s): Yamamoto T, Akisue O, Marui T, Kawamoto T, Nagira K, Nakagawa A, Yoshiya S, Kurosaka M. Source: The Journal of Rheumatology. 2003 June; 30(6): 1351-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784415&dopt=Abstract
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Sudden onset visual impairment and deafness in a patient with “long standing rheumatoid arthritis”. Author(s): Gaitonde S, Joshi VR. Source: J Assoc Physicians India. 2003 February; 51: 178-82. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725263&dopt=Abstract
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Suicides in persons suffering from rheumatoid arthritis. Author(s): Timonen M, Viilo K, Hakko H, Sarkioja T, Ylikulju M, Meyer-Rochow VB, Vaisanen E, Rasanen P. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 287-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595624&dopt=Abstract
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Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis. Author(s): Ho CY, Wong CK, Li EK, Tam LS, Lam CW. Source: Clinical and Experimental Immunology. 2003 July; 133(1): 132-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823287&dopt=Abstract
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Surgical management of cataracts in children with juvenile rheumatoid arthritisassociated uveitis. Author(s): Lam LA, Lowder CY, Baerveldt G, Smith SD, Traboulsi EI. Source: American Journal of Ophthalmology. 2003 June; 135(6): 772-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788115&dopt=Abstract
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Survival in fibrosing alveolitis associated with rheumatoid arthritis is better than cryptogenic fibrosing alveolitis. Author(s): Saravanan V, Kelly CA. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 603-4; Author Reply 604-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649414&dopt=Abstract
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Sympathetic skin response and R-R interval variation in cases with rheumatoid arthritis. Author(s): Gozke E, Erdogan N, Akyuz G, Turan B, Akyuz E, Us O. Source: Electromyogr Clin Neurophysiol. 2003 March; 43(2): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661131&dopt=Abstract
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Synergistic induction of apoptosis of rheumatoid arthritis synovial cells by H(2)O(2) and N-acetyl-leucyl-leucyl-norleucinal. Author(s): Akaike A, Banno Y, Osawa Y, Oshita H, Fushimi K, Kodama H, Shimizu K. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(3): 346-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768477&dopt=Abstract
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Synovial fluid exoglycosidases are predictors of rheumatoid arthritis and are effective in cartilage glycosaminoglycan depletion. Author(s): Ortutay Z, Polgar A, Gomor B, Geher P, Lakatos T, Glant TT, Gay RE, Gay S, Pallinger E, Farkas C, Farkas E, Tothfalusi L, Kocsis K, Falus A, Buzas EI. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2163-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905469&dopt=Abstract
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Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. Author(s): Pablos JL, Santiago B, Galindo M, Torres C, Brehmer MT, Blanco FJ, GarciaLazaro FJ. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 February 15; 170(4): 214752. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574387&dopt=Abstract
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Systematic review of celecoxib for osteoarthritis and rheumatoid arthritis. Celecoxib's relative gastrointestinal safety is overstated. Author(s): Metcalfe S, Dougherty S, McNee W. Source: Bmj (Clinical Research Ed.). 2003 February 8; 326(7384): 334; Author Reply 334. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575714&dopt=Abstract
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Systematic review of celecoxib for osteoarthritis and rheumatoid arthritis. Problems compromise review's validity. Author(s): Juni P, Sterchi R, Dieppe P. Source: Bmj (Clinical Research Ed.). 2003 February 8; 326(7384): 334; Author Reply 334. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574052&dopt=Abstract
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Systemic and local expression of perforin in lymphocyte subsets in acute and chronic rheumatoid arthritis. Author(s): Gulan G, Ravlic-Gulan J, Strbo N, Sotosek V, Nemec B, Matovinovic D, Rubinic D, Podack ER, Rukavina D. Source: The Journal of Rheumatology. 2003 April; 30(4): 660-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672182&dopt=Abstract
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T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients. Author(s): Munoz-Valle JF, Vazquez-Del Mercado M, Garcia-Iglesias T, Orozco-Barocio G, Bernard-Medina G, Martinez-Bonilla G, Bastidas-Ramirez BE, Navarro AD, Bueno M, Martinez-Lopez E, Best-Aguilera CR, Kamachi M, Armendariz-Borunda J. Source: Clinical and Experimental Immunology. 2003 February; 131(2): 377-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562402&dopt=Abstract
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Tackling ischaemic heart disease in rheumatoid arthritis. Author(s): Kitas GD, Erb N. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 607-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709534&dopt=Abstract
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Teasing apart the complex genetics of human autoimmunity: lessons from rheumatoid arthritis. Author(s): Gregersen PK. Source: Clinical Immunology (Orlando, Fla.). 2003 April; 107(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738244&dopt=Abstract
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The “Braids Lady” of Arezzo: a case of rheumatoid arthritis in a 16th century mummy. Author(s): Ciranni R, Garbini F, Neri E, Melai L, Giusti L, Fornaciari G. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 745-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508764&dopt=Abstract
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The “X-Ray RheumaCoach” software: a novel tool for enhancing the efficacy and accelerating radiological quantification in rheumatoid arthritis. Author(s): Wick M, Peloschek P, Bogl K, Graninger W, Smolen JS, Kainberger F. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 579-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759300&dopt=Abstract
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The -308 polymorphism in the tumour necrosis factor (TNF) gene promoter region and ex vivo lipopolysaccharide-induced TNF expression and cytotoxic activity in Chilean patients with rheumatoid arthritis. Author(s): Cuenca J, Cuchacovich M, Perez C, Ferreira L, Aguirre A, Schiattino I, Soto L, Cruzat A, Salazar-Onfray F, Aguillon JC. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 308-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595628&dopt=Abstract
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The assessment of rheumatoid arthritis and the acceptability of self-report questionnaires in clinical practice. Author(s): Wolfe F, Pincus T, Thompson AK, Doyle J. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579594&dopt=Abstract
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The association of myasthenia gravis and connective tissue diseases. Effects of thymectomy in six cases with rheumatoid arthritis and one case with systemic lupus erythematosus. Author(s): Tellez-Zenteno JF, Remes-Troche JM, Mimenza-Alvarado A, Garcia-Ramos G, Estanol B, Vega-Boada F. Source: Neurologia (Barcelona, Spain). 2003 March; 18(2): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610753&dopt=Abstract
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The case against haste in the treatment of rheumatoid arthritis: comment on the editorial by Pincus et al. Author(s): Epstein WV. Source: Arthritis and Rheumatism. 2003 February; 48(2): 573-5; Author Reply 576-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571870&dopt=Abstract
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The cost effectiveness of rofecoxib and celecoxib in patients with osteoarthritis or rheumatoid arthritis. Author(s): Maetzel A, Krahn M, Naglie G. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 283-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794781&dopt=Abstract
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The cost-effectiveness of infliximab (Remicade) in the treatment of rheumatoid arthritis in Sweden and the United Kingdom based on the ATTRACT study. Author(s): Kobelt G, Jonsson L, Young A, Eberhardt K. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 326-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595631&dopt=Abstract
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The development and evaluation of a drug information leaflet for patients with rheumatoid arthritis. Author(s): Hill J, Bird H. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509615&dopt=Abstract
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The effect of treatment on radiological progression in rheumatoid arthritis: a systematic review of randomized placebo-controlled trials. Author(s): Jones G, Halbert J, Crotty M, Shanahan EM, Batterham M, Ahern M. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 6-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509606&dopt=Abstract
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The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year followup study. Author(s): Kalden JR, Schattenkirchner M, Sorensen H, Emery P, Deighton C, Rozman B, Breedveld F. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1513-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794818&dopt=Abstract
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The fate of the distal extensor retinaculum in dorsal wrist procedures for rheumatoid arthritis. Author(s): Skillman JM, Belcher HJ. Source: British Journal of Plastic Surgery. 2003 January; 56(1): 70-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706161&dopt=Abstract
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The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis. Author(s): Korendowych E, Dixey J, Cox B, Jones S, McHugh N. Source: The Journal of Rheumatology. 2003 January; 30(1): 96-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508396&dopt=Abstract
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The JAK/STAT pathway in rheumatoid arthritis: pathogenic or protective? Author(s): Ivashkiv LB, Hu X. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2092-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905460&dopt=Abstract
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The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis. Author(s): Dayer JM. Source: Rheumatology (Oxford, England). 2003 May; 42 Suppl 2: Ii3-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817089&dopt=Abstract
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The power of the third dimension: tissue architecture and autoimmunity in rheumatoid arthritis. Author(s): Weyand CM, Kang YM, Kurtin PJ, Goronzy JJ. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 259-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707579&dopt=Abstract
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The prevalence of patients with rheumatoid arthritis in the West Midlands fulfilling the BSR criteria for anti-tumour necrosis factor therapy: an out-patient study. Author(s): Yee CS, Filer A, Pace A, Douglas K, Situnayake D, Rowe IF; West Midlands Rheumatology Services and Training Committee. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 856-9. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730544&dopt=Abstract
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The responsiveness of generic health status measures as assessed in patients with rheumatoid arthritis receiving infliximab. Author(s): Russell AS, Conner-Spady B, Mintz A, Maksymowych WP. Source: The Journal of Rheumatology. 2003 May; 30(5): 941-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734886&dopt=Abstract
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The RoentgenCoach-Rheumatology--a novel tool to enhance efficacy of radiological scoring of rheumatoid arthritis. Results of experimental scoring of 72 cases. Author(s): Peloschek P, Bogl K, Sailer J, Wick M, Graninger W, Robinson S, Lomoschitz F, Bohm P, Kainberger F, Imhof H. Source: Acta Orthop Scand Suppl. 2002 October; 73(305): 58-62. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545667&dopt=Abstract
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The role of COX-2 in angiogenesis and rheumatoid arthritis. Author(s): Woods JM, Mogollon A, Amin MA, Martinez RJ, Koch AE. Source: Experimental and Molecular Pathology. 2003 June; 74(3): 282-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782016&dopt=Abstract
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The role of free radicals in the pathogenesis of rheumatoid arthritis. Author(s): Hadjigogos K. Source: Panminerva Medica. 2003 March; 45(1): 7-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682616&dopt=Abstract
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The role of HLA-DRB1*04 alleles and their association with HLA-DQB genes in genetic susceptibility to rheumatoid arthritis in Hungarian patients. Author(s): Varga E, Palkonyai E, Temesvari P, Toth F, Petri IB. Source: Acta Microbiol Immunol Hung. 2003; 50(1): 33-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793199&dopt=Abstract
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The safety and efficacy of chicken type II collagen on uveitis associated with juvenile rheumatoid arthritis. Author(s): Thompson DJ, Barron KS, Whitcup SM, Robinson MR. Source: Ocular Immunology and Inflammation. 2002 June; 10(2): 83-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778344&dopt=Abstract
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The therapeutic potential of costimulatory blockade with CTLA4Ig in rheumatoid arthritis. Author(s): Emery P. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 673-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665422&dopt=Abstract
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The therapeutic potential of TNF-alpha blockade in rheumatoid arthritis. Author(s): Paleolog E. Source: Expert Opinion on Investigational Drugs. 2003 July; 12(7): 1087-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831345&dopt=Abstract
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The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practice patterns and pregnancy outcomes. Author(s): Chakravarty EF, Sanchez-Yamamoto D, Bush TM. Source: The Journal of Rheumatology. 2003 February; 30(2): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563675&dopt=Abstract
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The use of rheumatoid arthritis health-related quality of life patient questionnaires in clinical practice: lessons learned. Author(s): Russak SM, Croft JD Jr, Furst DE, Hohlbauch A, Liang MH, Moreland L, Ofman JJ, Paulus H, Simon LS, Weisman M, Tugwell P; Evidence-Based Medicine Working Groups in Rheumatology. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 574-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910566&dopt=Abstract
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Therapeutic strategies for rheumatoid arthritis. Author(s): Smolen JS, Steiner G. Source: Nature Reviews. Drug Discovery. 2003 June; 2(6): 473-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776222&dopt=Abstract
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Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alphainduced angiogenesis in rheumatoid arthritis. Author(s): DeBusk LM, Chen Y, Nishishita T, Chen J, Thomas JW, Lin PC. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2461-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130465&dopt=Abstract
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Time of onset of uveitis in children with juvenile rheumatoid arthritis. Author(s): Kodsi SR, Rubin SE, Milojevic D, Ilowite N, Gottlieb B. Source: J Aapos. 2002 December; 6(6): 373-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506279&dopt=Abstract
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Time trends in disability pensioning for rheumatoid arthritis, osteoarthritis and soft tissue rheumatism in Norway 1968-97. Author(s): Holte HH, Tambs K, Bjerkedal T. Source: Scandinavian Journal of Public Health. 2003; 31(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623520&dopt=Abstract
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TNF +489 polymorphism does not contribute to susceptibility to rheumatoid arthritis. Author(s): Low AS, Gonzalez-Gay MA, Akil M, Amos RS, Bax DE, Cannings C, Hajeer A, Till SH, Winfield J, Ollier WE, Wilson AG. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 829-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508775&dopt=Abstract
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Total knee arthroplasty in young patients with juvenile rheumatoid arthritis. Author(s): Parvizi J, Lajam CM, Trousdale RT, Shaughnessy WJ, Cabanela ME. Source: The Journal of Bone and Joint Surgery. American Volume. 2003 June; 85-A(6): 1090-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784008&dopt=Abstract
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Toxicity profiles of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. Author(s): Aletaha D, Kapral T, Smolen JS. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 482-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695166&dopt=Abstract
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Transcendence and transformation in the life patterns of women living with rheumatoid arthritis. Author(s): Neill J. Source: Ans. Advances in Nursing Science. 2002 June; 24(4): 27-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699275&dopt=Abstract
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Transforming growth factor beta 1 gene (HSTGFB1) nucleotide T869C (codon 10) polymorphism is not associated with prevalence or severity of rheumatoid arthritis in a Caucasian population. Author(s): Pokorny V, Chau J, Wu L, Yeoman S, Black P, McQueen F, McLean L. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 907-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922971&dopt=Abstract
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Transoral approach using the mandibular osteotomy for atlantoaxial vertical subluxation in juvenile rheumatoid arthritis associated with mandibular micrognathia. Author(s): Kanamori Y, Miyamoto K, Hosoe H, Fujitsuka H, Tatematsu N, Shimizu K. Source: Journal of Spinal Disorders & Techniques. 2003 April; 16(2): 221-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679681&dopt=Abstract
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Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter activesurveillance report. Author(s): Gomez-Reino JJ, Carmona L, Valverde VR, Mola EM, Montero MD; BIOBADASER Group. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905464&dopt=Abstract
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Tumor necrosis factor receptor 2 microsatellite and exon 6 polymorphisms in rheumatoid arthritis in Taiwan. Author(s): Yen JH, Tsai WC, Chen CJ, Ou TT, Lin CH, Hu CJ, Liu HW. Source: The Journal of Rheumatology. 2003 March; 30(3): 438-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610797&dopt=Abstract
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Tumour necrosis factor-alpha, interleukin-2 soluble receptor and different inflammatory parameters in patients with rheumatoid arthritis. Author(s): Frode TS, Tenconi P, Debiasi MR, Medeiros YS. Source: Mediators of Inflammation. 2002 December; 11(6): 345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581498&dopt=Abstract
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Twenty eight joint count disease activity score in recent onset rheumatoid arthritis using C reactive protein instead of erythrocyte sedimentation rate. Author(s): Skogh T, Gustafsson D, Kjellberg M, Husberg M. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 681-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810437&dopt=Abstract
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Two injections of interferon-alpha could trigger the development of rheumatoid arthritis. Author(s): Funauchi M, Ohno M, Nozaki Y, Kinoshita K, Sugiyama M, Kanamaru A. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 871. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508785&dopt=Abstract
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Two year randomized controlled trial of etidronate in rheumatoid arthritis: changes in serum aminoterminal telopeptides correlate with radiographic progression of disease. Author(s): Valleala H, Laasonen L, Koivula MK, Mandelin J, Friman C, Risteli J, Konttinen YT. Source: The Journal of Rheumatology. 2003 March; 30(3): 468-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610803&dopt=Abstract
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Ultrasonography is superior to clinical examination in the detection and localization of knee joint effusion in rheumatoid arthritis. Author(s): Kane D, Balint PV, Sturrock RD. Source: The Journal of Rheumatology. 2003 May; 30(5): 966-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734890&dopt=Abstract
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Ultrasonography of the hip in the evaluation of children with seronegative juvenile rheumatoid arthritis. Author(s): Friedman S, Gruber MA. Source: The Journal of Rheumatology. 2002 March; 29(3): 629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908582&dopt=Abstract
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Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis. Author(s): Frediani B, Falsetti P, Storri L, Allegri A, Bisogno S, Baldi F, Marcolongo R. Source: Clinical Rheumatology. 2002 August; 21(4): 294-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189456&dopt=Abstract
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Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis. Author(s): Frediani B, Falsetti P, Storri L, Allegri A, Bisogno S, Baldi F, Marcolongo R. Source: Clinical Rheumatology. 2002 June; 21(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111624&dopt=Abstract
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Understanding the window of opportunity concept in early rheumatoid arthritis. Author(s): Boers M. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1771-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847667&dopt=Abstract
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Unusual case of cutaneous tuberculosis associated with rheumatoid arthritis: a case report and literature review. Author(s): Faghihi G, Yoosefi A. Source: International Journal of Dermatology. 2002 December; 41(12): 913-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492987&dopt=Abstract
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Unwillingness of rheumatoid arthritis patients to risk adverse effects. Author(s): Fraenkel L, Bogardus S, Concato J, Felson D. Source: Rheumatology (Oxford, England). 2002 March; 41(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934960&dopt=Abstract
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Updated consensus statement on biological agents for the treatment of rheumatoid arthritis and other rheumatic diseases (May 2002). Author(s): Furst DE, Breedveld FC, Kalden JR, Smolen JS, Antoni CE, Bijlsma JW, Burmester GR, Cronstein B, Keystone EC, Kavanaugh A, Klareskog L. Source: Annals of the Rheumatic Diseases. 2002 November; 61 Suppl 2: Ii2-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379612&dopt=Abstract
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Updated consensus statement on tumour necrosis factor blocking agents for the treatment of rheumatoid arthritis and other rheumatic diseases (April 2001). Author(s): Furst DE, Keystone EC, Breedveld FC, Kalden JR, Smolen JS, Antoni CE, Burmester GR, Crofford LJ, Kavanaugh A. Source: Annals of the Rheumatic Diseases. 2001 November; 60 Suppl 3: Iii2-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890647&dopt=Abstract
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Upper gastrointestinal tolerability of celecoxib compared with diclofenac in the treatment of osteoarthritis and rheumatoid arthritis. Author(s): McKenna F, Arguelles L, Burke T, Lefkowith J, Geis GS. Source: Clin Exp Rheumatol. 2002 January-February; 20(1): 35-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892706&dopt=Abstract
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Urgent care and tight control of rheumatoid arthritis as in diabetes and hypertension: better treatments but a shortage of rheumatologists. Author(s): Pincus T, Gibofsky A, Weinblatt ME. Source: Arthritis and Rheumatism. 2002 April; 46(4): 851-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953958&dopt=Abstract
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Use of biologics for rheumatoid arthritis tempered by concerns over safety, cost. Author(s): Pressman Lovinger S. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824197&dopt=Abstract
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Use of cognitive-behavioural arthritis education programmes in newly diagnosed rheumatoid arthritis. Author(s): Freeman K, Hammond A, Lincoln NB. Source: Clinical Rehabilitation. 2002 December; 16(8): 828-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501944&dopt=Abstract
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Use of isokinetic muscle strength as a measure of severity of rheumatoid arthritis: a comparison of this assessment method for RA with other assessment methods for the disease. Author(s): Schiottz-Christensen B, Lyngberg K, Keiding N, Ebling AH, DanneskioldSamsoe B, Bartels EM. Source: Clinical Rheumatology. 2001; 20(6): 423-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771527&dopt=Abstract
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Use of prognostic markets to guide biologic therapies for rheumatoid arthritis. Author(s): D'Arcy CA, Willkens RF. Source: The Journal of Rheumatology. 2002 December; 29(12): 2662; Author Reply 26623. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465172&dopt=Abstract
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Using anakinra for adult rheumatoid arthritis. Author(s): Kastanek L. Source: The Nurse Practitioner. 2002 April; 27(4): 62-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984420&dopt=Abstract
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Using estimated yearly progression rates to compare radiographic data across recent randomised controlled trials in rheumatoid arthritis. Author(s): Strand V, Landewe R, van der Heijde D. Source: Annals of the Rheumatic Diseases. 2002 November; 61 Suppl 2: Ii64-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379626&dopt=Abstract
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Vaccination and rheumatoid arthritis. Author(s): Sibilia J, Maillefert JF. Source: Annals of the Rheumatic Diseases. 2002 July; 61(7): 575-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079893&dopt=Abstract
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Validation of a novel satisfaction questionnaire for patients with rheumatoid arthritis receiving outpatient clinical nurse specialist care, inpatient care, or day patient team care. Author(s): Tijhuis GJ, Kooiman KG, Zwinderman AH, Hazes JM, Breedveld FC, Vliet Vlieland TP. Source: Arthritis and Rheumatism. 2003 April 15; 49(2): 193-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687510&dopt=Abstract
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Validation of an Indian version of the Health Assessment Questionnaire in patients with rheumatoid arthritis. Author(s): Kumar A, Malaviya AN, Pandhi A, Singh R. Source: Rheumatology (Oxford, England). 2002 December; 41(12): 1457-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468833&dopt=Abstract
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Validity of the Nottingham Health Profile in a Finnish out-patient population with rheumatoid arthritis. Author(s): Uutela T, Hakala M, Kautiainen H. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 841-5. Epub 2003 May 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759465&dopt=Abstract
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Value of dynamic splinting after replacement of the metacarpophalangeal joint in patients with rheumatoid arthritis. Author(s): Thomsen NO, Boeckstyns ME, Leth-Espensen P. Source: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery / Nordisk Plastikkirurgisk Forening [and] Nordisk Klubb for Handkirurgi. 2003; 37(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755512&dopt=Abstract
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Value of laboratory tests in early prediction of rheumatoid arthritis. Author(s): Saraux A, Berthelot JM, Chales G, Le Henaff C, Mary JY, Thorel JB, Hoang S, Dueymes M, Allain J, Devauchelle V, Baron D, Le Goff P, Youinou P. Source: Arthritis and Rheumatism. 2002 April 15; 47(2): 155-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954009&dopt=Abstract
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Variant mannose-binding lectin genotypes and outcome in early versus late rheumatoid arthritis: comment on the article by Ip et al. Author(s): Graudal NA, Garred P, Madsen HO, Svejgaard A, Tarp U, Jurik AG, Graudal HK. Source: Arthritis and Rheumatism. 2002 February; 46(2): 555-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840460&dopt=Abstract
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Vasculitis secondary to staphylococcal Protein A immunoadsorption (Prosorba column) treatment in rheumatoid arthritis. Author(s): Deodhar A, Allen E, Daoud K, Wahba I. Source: Seminars in Arthritis and Rheumatism. 2002 August; 32(1): 3-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219317&dopt=Abstract
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VEGF and imaging of vessels in rheumatoid arthritis. Author(s): Taylor PC. Source: Arthritis Research. 2002; 4 Suppl 3: S99-107. Epub 2002 May 09. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110128&dopt=Abstract
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Vertebral deformities in 229 female patients with rheumatoid arthritis: associations with clinical variables and bone mineral density. Author(s): Orstavik RE, Haugeberg G, Uhlig T, Falch JA, Halse JI, Hoiseth A, Lilleas F, Kvien TK. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 355-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794791&dopt=Abstract
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Vestibulo-ocular, optokinetic and postural function in humans with rheumatoid arthritis. Author(s): King J, Young C, Highton J, Smith PF, Darlington CL. Source: Neuroscience Letters. 2002 August 9; 328(2): 77-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133559&dopt=Abstract
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Vitamin D receptor genotypes are not associated with rheumatoid arthritis or biochemical parameters of bone turnover in German RA patients. Author(s): Goertz B, Fassbender WJ, Williams JC, Marzeion AM, Bretzel RG, Stracke H, Berliner MN. Source: Clin Exp Rheumatol. 2003 May-June; 21(3): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846052&dopt=Abstract
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VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients. Author(s): Takeuchi E, Tanaka T, Umemoto E, Tomita T, Shi K, Takahi K, Suzuki R, Ochi T, Miyasaka M. Source: Arthritis Research. 2002; 4(6): R10. Epub 2002 August 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453313&dopt=Abstract
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Weekly dose of leflunomide for the treatment of refractory rheumatoid arthritis: an open pilot comparative study. Author(s): Jakez-Ocampo J, Richaud-Patin Y, Simon JA, Llorente L. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 May; 69(3): 307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102278&dopt=Abstract
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Wegener's granulomatosis and rheumatoid arthritis overlap. Author(s): Chinoy H, McKenna F. Source: Rheumatology (Oxford, England). 2002 May; 41(5): 588-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011387&dopt=Abstract
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What are the risks of biologic therapy in rheumatoid arthritis? An update on safety. Author(s): Weisman MH. Source: J Rheumatol Suppl. 2002 September; 65: 33-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236621&dopt=Abstract
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What can we learn from the synovium in early rheumatoid arthritis? Author(s): Katrib A, McNeil HP, Youssef PP. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 April; 51(4): 170-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058953&dopt=Abstract
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What employees with rheumatoid arthritis, diabetes mellitus and hearing loss need to cope at work. Author(s): Detaille SI, Haafkens JA, van Dijk FJ. Source: Scand J Work Environ Health. 2003 April; 29(2): 134-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718499&dopt=Abstract
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Which patients stop working because of rheumatoid arthritis? Results of five years' follow up in 732 patients from the Early RA Study (ERAS). Author(s): Young A, Dixey J, Kulinskaya E, Cox N, Davies P, Devlin J, Emery P, Gough A, James D, Prouse P, Williams P, Winfield J. Source: Annals of the Rheumatic Diseases. 2002 April; 61(4): 335-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874837&dopt=Abstract
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Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom. Author(s): MacKay K, Eyre S, Myerscough A, Milicic A, Barton A, Laval S, Barrett J, Lee D, White S, John S, Brown MA, Bell J, Silman A, Ollier W, Wordsworth P, Worthington J. Source: Arthritis and Rheumatism. 2002 March; 46(3): 632-9. Erratum In: Arthritis Rheum 2002 May; 46(5): 1406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920398&dopt=Abstract
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Why do we not have a cure for rheumatoid arthritis? Author(s): El-Gabalawy HD, Lipsky PE. Source: Arthritis Research. 2002; 4 Suppl 3: S297-301. Epub 2002 May 09. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110149&dopt=Abstract
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Will pharmacogenetics allow better prediction of methotrexate toxicity and efficacy in patients with rheumatoid arthritis? Author(s): Ranganathan P, Eisen S, Yokoyama WM, McLeod HL. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 4-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480661&dopt=Abstract
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Women with established rheumatoid arthritis perceive pain as the predominant impairment of health status. Author(s): Minnock P, FitzGerald O, Bresnihan B. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 995-1000. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730516&dopt=Abstract
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Yellow nail syndrome associated with thiol compound therapy for rheumatoid arthritis. Two case reports. Author(s): Lehuede G, Toussirot E, Despaux J, Michel F, Wendling D. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 June; 69(4): 406-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184439&dopt=Abstract
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CHAPTER 2. NUTRITION AND RHEUMATOID ARTHRITIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and rheumatoid arthritis.
Finding Nutrition Studies on Rheumatoid Arthritis The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “rheumatoid arthritis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on rheumatoid arthritis: •
Breastfeeding-related onset, flare, and relapse of rheumatoid arthritis. Author(s): Department of Nutrition, Arizona State University, Mesa 85212, USA. Source: Hampl, J S Papa, D J Nutr-Revolume 2001 August; 59(8 Pt 1): 264-8 0029-6643
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Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. Author(s): Loyola University Medical Center, Maywood, IL 60153, USA. Source: Tidow Kebritchi, S Mobarhan, S Nutr-Revolume 2001 October; 59(10): 335-8 0029-6643
The following information is typical of that found when using the “Full IBIDS Database” to search for “rheumatoid arthritis” (or a synonym): •
A 7-day oral treatment of patients with active rheumatoid arthritis using the prostacyclin analog iloprost: cytokine modulation, safety, and clinical effects. Author(s): Rheumatology Practice, Dossenheimer Landstr. 100, 69121 Heidelberg, Germany.
[email protected] Source: Gao, I K Scholz, P Boehme, M W Norden, C Lemmel, E M Rheumatol-Int. 2002 June; 22(2): 45-51 0172-8172
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A combination therapy for chronic rheumatoid arthritis with selenium and allogeneic lymphocytes. Source: Kondo, M. Selenium in biology and medicine : proceedings of the Third International Symposium on Selenium in Biology and Medicine, held May 27-June 1, 1984, Xiangshan (Fragrance Hills) Hotel Beijing, People's Republic of China. New York : Van Nostrand Reinhold, c1987. page 992-995. ISBN: 0442221088
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A phase I/IIa study on intra-articular injection of holmium-166-chitosan complex for the treatment of knee synovitis of rheumatoid arthritis. Author(s): Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-ku, 120-752, Seoul, Korea. Source: Song, J Suh, C H Park, Y B Lee, S H Yoo, N C Lee, J D Kim, K H Lee, S K Eur-JNucl-Med. 2001 April; 28(4): 489-97 0340-6997
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A preliminary study of circadian serum cortisol concentrations in response to a 72hour fast in rheumatoid arthritis patients not previously treated with corticosteroids. Author(s): Centre for Rheumatic Diseases, National Hospital, Oslo, Norway.
[email protected] Source: Fraser, D A Thoen, J Selvaag, A M Djoseland, O Forre, O Kjeldsen Kragh, J ClinRheumatol. 2001; 20(2): 85-7 0770-3198
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A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Author(s): Department of Rheumatology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden. Source: Hafstrom, I Ringertz, B Spangberg, A von Zweigbergk, L Brannemark, S Nylander, I Ronnelid, J Laasonen, L Klareskog, L Rheumatology-(Oxford). 2001 October; 40(10): 1175-9 1462-0324
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Acupuncture and other alternative therapies in rheumatoid arthritis. Author(s): Barnsley District General Hospital NHS Trust, Barnsley. Source: Hardware, Bernadette Lacey, Anne Prof-Nurse. 2002 March; 17(7): 437-9 02668130
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Acute iridocyclitis in antinuclear antibody-positive pauciarticular juvenile rheumatoid arthritis detected a decade earlier. Author(s): Alberto Moscona Department of Ophthalmology, Rambam Medical Center, Haifa, Israel. Source: Schaal, S Beiran, I Brik, R Miller, B J-Pediatr-Ophthalmol-Strabismus. 2002 NovDecember; 39(6): 365-6 0191-3913
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Advances in TCM symptomatology of rheumatoid arthritis. Author(s): Institute of Bioinformatics, Tsinghua University, Beijing 100084. Source: Li, S J-Tradit-Chin-Med. 2002 June; 22(2): 137-42 0254-6272
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Analysis of cartilage-derived retinoic-acid-sensitive protein (CD-RAP) in synovial fluid from patients with osteoarthritis and rheumatoid arthritis. Author(s): Department of Surgery, Nagoya University School of Medicine, Japan. Source: Saito, S Kondo, S Mishima, S Ishiguro, N Hasegawa, Y Sandell, L J Iwata, H JBone-Joint-Surg-Br. 2002 September; 84(7): 1066-9 0301-620X
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Attained adult height in juvenile rheumatoid arthritis with or without corticosteroid treatment. Author(s): National Taiwan University Hospital, Taipei, Taiwan. Source: Wang, S J Yang, Y H Lin, Y T Yang, C M Chiang, B L Clin-Rheumatol. 2002 September; 21(5): 363-8 0770-3198
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Bilateral tibia and fibula fractures in a patient with rheumatoid arthritis. Author(s): Department of Rheumatology, Frimley Park Hospital. Frimley, Surrey, UK.
[email protected] Source: Lloyd, M E Davitt, S Hall, J R Clin-Rheumatol. 2001; 20(4): 270-2 0770-3198
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Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. Author(s): Department of Psychiatry, College of Medicine, University of Vermont, Burlington 05401, USA.
[email protected] Source: Kast, R E Int-Immunopharmacol. 2001 November; 1(12): 2197-9 1567-5769
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Can we induce tolerance in rheumatoid arthritis? Author(s): Department of Medicine, Division of Connective Tissue Diseases, University of Tennessee Memphis, and Department of Veterans Affairs Medical Center, 956 Court Ave, Room G 326, Memphis, TN 38163, USA.
[email protected] Source: Postlethwaite, A E Curr-Rheumatol-Repage 2001 February; 3(1): 64-9 1523-3774
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Clinical trials for the treatment of systemic onset juvenile rheumatoid arthritisjuvenile idiopathic arthritis. Author(s): Division of Pediatric Rheumatology, Hospital for Special Surgery, and Sanford Weill Medical College of Cornell University, 535 East 70th Street, New York, NY 10021, USA.
[email protected] Source: Lehman, T J Curr-Rheumatol-Repage 2000 August; 2(4): 313-5 1523-3774
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Different doses of fish-oil fatty acid ingestion in active rheumatoid arthritis: a prospective study of clinical and immunological parameters. Source: Kremer, J.M. Lawrence, D.A. Jubiz, W. NATO-ASI-Ser-Ser-A-Life-Sci. New York, N.Y. : Plenum Press. 1989. volume 171 page 343-350.
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Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis. Author(s): Department of Pathology, Iwate Medical University, Morioka, Japan.
[email protected]
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Source: Kurose, A Yoshida, W Yoshida, M Sawai, T Cytometry. 2001 August 1; 44(4): 349-54 0196-4763 •
Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis. Author(s): Center of Immunology, Institute of Virology St. S. Nicolau, Bucharest, Romania.
[email protected] Source: Bostan, M Brasoveanu, L I Livescu, A Manda, G Neagu, M Iordachescu, D JCell-Mol-Med. 2001 Apr-June; 5(2): 188-94 1582-1838
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Elk velvet antler in rheumatoid arthritis: phase II trial. Author(s): Faculty of Nursing, University of Alberta, Edmonton, Canada.
[email protected] Source: Allen, Marion Oberle, Kathleen Grace, Michael Russell, Anthony Biol-Res-Nurs. 2002 January; 3(3): 111-8 1099-8004
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Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Author(s): University of Manchester Medical School, Oxford Road, Manchester, M13 9PT, UK. Source: Symmons, D P Best-Pract-Res-Clin-Rheumatol. 2002 December; 16(5): 707-22 1521-6942
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Essential fatty acid and prostaglandin metabolism in Sjogren's syndrome, systemic sclerosis and rheumatoid arthritis. Source: Horrobin, D F Scand-J-Rheumatol-Suppl. 1986; 61: 242-5 0301-3847
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Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients. Author(s): Department of Rheumatology, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara.
[email protected] Source: Ramos Remus, C Dorazco Barragan, G Aceves Avila, F J Alcaraz Lopez, F Fuentes Ramirez, F Michel Diaz, J Torres Bugarin, O Ventura Aguilar, A Zuniga Gonzalez, G Clin-Exp-Rheumatol. 2002 Mar-April; 20(2): 208-12 0392-856X
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Gibt es sinnvolle Diatvorschlage fur Patienten mit rheumatoider Arthritis? [Are there effective dietary recommendations for patients with rheumatoid arthritis?] Author(s): Universitatsklinikum Krollwitz, Klinik und Poliklinik fur Innere Medizin I, Ernst-Grube-Str. 40, 06097 Halle/S.
[email protected] Source: Keysser, G Z-Rheumatol. 2001 February; 60(1): 17-27 0340-1855
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Glucocorticoid use in rheumatoid arthritis. Author(s): Division of Clinical Immunology and Rheumatology, Center for Education and Research on Therapeutics (CERTs) of Musculoskeletal Disorders, University of Alabama at Birmingham, MEB 625, 1813 Sixth Avenue South, Birmingham, AL 352943296, USA.
[email protected] Source: Saag, Kenneth G Curr-Rheumatol-Repage 2002 June; 4(3): 218-25 1523-3774
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Herbal therapy for treating rheumatoid arthritis. Author(s): Institute of Health & Community Studies, Bournemouth University, Bournemouth House, Bournemouth University, 17 Christchurch Road, Bournemouth, Dorset, UK, BH1 3LG.
[email protected] Source: Little, C Parsons, T Cochrane-Database-Syst-Revolume 2001; 1: CD002948 1469493X
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Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. Author(s): Department of Rheumatology, University Medical Center St Radboud, Nijmegen, The Netherlands. Source: van Ede, A E Laan, R F J M Blom, H J Boers, G H J Haagsma, C J Thomas, C M G De Boo, T M van de Putte, L B A Rheumatology-(Oxford). 2002 June; 41(6): 658-65 14620324
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Intra-articular injection of hyaluronate (SI-6601D) improves joint pain and synovial fluid prostaglandin E2 levels in rheumatoid arthritis: a multicenter clinical trial. Author(s): Division of Rheumatic Diseases, Tokyo Metropolitan Otsuka Hospital, Japan.
[email protected] Source: Goto, M Hanyu, T Yoshio, T Matsuno, H Shimizu, M Murata, N Shiozawa, S Matsubara, T Yamana, S Matsuda, T Clin-Exp-Rheumatol. 2001 Jul-August; 19(4): 377-83 0392-856X
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Klent underlag for att behandla reumatoid artrit med ortmedicin. [Meager support for herbal therapy of rheumatoid arthritis] Author(s): Reumatologiska kliniken, Universitetssjukhuset i Lund. Source: Wollheim, F A Lakartidningen. 2001 October 10; 98(41): 4434-6 0023-7205
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Leg ulceration in rheumatoid arthritis. Author(s): Royal National Hospital for Rheumatic Diseases NHS Trust, Bath. Source: Grange, M Henderson, C Nurs-Times. 2001 June 14-20; 97(24): 63 0954-7762
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Metabolism of kalopanaxsaponin K by human intestinal bacteria and antirheumatoid arthritis activity of their metabolites. Author(s): College of Pharmacy, Kyung-Hee University, Seoul, Korea.
[email protected] Source: Kim, Dong Hyun Bae, Eun Ah Han, Myung Joo Park, Hee Juhn Choi, Jong Won Biol-Pharm-Bull. 2002 January; 25(1): 68-71 0918-6158
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Multiple occlusive retinal arteritis in both eyes of a patient with rheumatoid arthritis. Author(s): Department of Ophthalmology, Okayama University Medical School, Okayama City, Japan. Source: Matsuo, T Jpn-J-Ophthalmol. 2001 Nov-December; 45(6): 662-4 0021-5155
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Non-prescription complementary treatments used by rheumatoid arthritis patients attending a community-based rheumatology practice. Author(s): Department of Clinical Epidemiology, Cabrini Hospital, Melbourne, Victoria, Australia.
[email protected] Source: Buchbinder, R Gingold, M Hall, S Cohen, M Intern-Med-J. 2002 May-June; 32(56): 208-14 1444-0903
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Nutritional status in patients with rheumatoid arthritis. Author(s): Rheumatology Department, Centre Sanitaire de l'Universite de Bellvitge, L'Hospitalet, Barcelona, Spain. Source: Gomez Vaquero, C Nolla, J M Fiter, J Ramon, J M Concustell, R Valverde, J Roig Escofet, D Joint-Bone-Spine. 2001 October; 68(5): 403-9 1297-319X
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Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis. Author(s): Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK. Source: Hirayama, T Danks, L Sabokbar, A Athanasou, N A Rheumatology-(Oxford). 2002 November; 41(11): 1232-9 1462-0324
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Pharmaceutical agents for the treatment of rheumatoid arthritis. Author(s): University of Kansas School of Medicine, USA. Source: Scott, T E Manag-Care. 2001 July; 10(7 Suppl): 2-9 1062-3388
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Radiographic outcome after three years of patients with early erosive rheumatoid arthritis treated with intramuscular methotrexate or parenteral gold. Extension of a one-year double-blind study in 174 patients. Author(s): Department of Rheumatology, Evangelisches Fachkrankenhaus, Ratingen, Germany. Source: Rau, R Herborn, G Menninger, H Sangha, O Rheumatology-(Oxford). 2002 February; 41(2): 196-204 1462-0324
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Retrospective study of adverse events in patients with rheumatoid arthritis treated with second-line drugs. Author(s): Zhongshan Hospital, Fudan University, Shanghai 200032, China. Source: Jiang, L Zhao, N Ni, L Zhonghua-Liu-Xing-Bing-Xue-Za-Zhi. 2002 June; 23(3): 213-7 0254-6450
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Rheumatoid arthritis and the older adult. Author(s): DI Associates Inc. in Hughesville, MD, USA. Source: Ignatavicius, D D Geriatr-Nurs. 2001 May-June; 22(3): 139-42 0197-4572
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Screening of some Turkish medicinal plants used in the treatment of rheumatoid arthritis and inflammatory diseases for their anti-inflammatory activities. Source: Yesilada, E. Sezik, E. Plant-Med. Stuttgart, W. Ger. : Georg Thieme Verlag. December 1990. volume 56 (6) page 659. 0032-0943
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Second-line drugs used in recent-onset rheumatoid arthritis in Brittany (France). Author(s): Rheumatology department of Brest, hjpital de la Cavale-Blanche, France.
[email protected] Source: Saraux, Alain Berthelot, Jean Marie Chales, Gerard Le, Henaff Catherine Thorel, Jean Hoang, Sylvie Martin, Antoine Allain, Jerjme Nouy Trolle, Isabelle Devauchelle, Valerie Youinou, Pierre Le, Goff Paul Joint-Bone-Spine. 2002 January; 69(1): 37-42 1297319X
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Sex hormone adjuvanting therapy in rheumatoid arthritis. Author(s): Department of Internal Medicine, University
[email protected] Source: Cutolo, M Lupus. 2002; 11(10): 670-4 0961-2033
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The development and evaluation of a drug information leaflet for patients with rheumatoid arthritis. Author(s): Clinical Pharmacology Unit (Rheumatism Research, University of Leeds), Chapel Allerton Hospital, Chapeltown Road, Leeds, West Yorkshire LS7 4SA, UK.
[email protected] Source: Hill, J Bird, H Rheumatology-(Oxford). 2003 January; 42(1): 66-70 1462-0324
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The problem of empyematous pleural effusion in rheumatoid arthritis: report of two cases and review of the literature. Author(s): Department of Pulmonary Medicine, Rambam Medical Center and Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
[email protected] Source: Yigla, M Simsolo, C Goralnik, L Balabir German, A Nahir, A M Clin-Rheumatol. 2002 May; 21(2): 180-3 0770-3198
of
Genova,
Italy.
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The rheumatoid arthritis patient in the clinic: comparing more than 1,300 consecutive DMARD courses. Author(s): Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna, Austria. Source: Aletaha, D Smolen, J S Rheumatology-(Oxford). 2002 December; 41(12): 1367-74 1462-0324
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The therapeutic approach of early intervention for rheumatoid arthritis: what is the evidence? Author(s): Rheumatology and Rehabilitation Research Unit, University of Leeds, Leeds, UK. Source: Quinn, M A Conaghan, P G Emery, P Rheumatology-(Oxford). 2001 November; 40(11): 1211-20 1462-0324
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The use of low-dose prednisone in the management of rheumatoid arthritis. Author(s): Emory University School of Medicine, Atlanta, GA, USA. Source: Lim, S S Conn, D L Bull-Rheum-Dis. 2001; 50(12): 1-4 0007-5248
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Trabecular bone density in premenopausal rheumatoid arthritis patients. Author(s): Department of Medicine, Rheumatic Diseases Unit, Groote Schuur Hospital, University of Cape Town. Source: Kalla, A A Bewerunge, L Langley, A Meyers, O L Fataar, A B S-Afr-Med-J. 2002 January; 92(1): 62-8 0038-2469
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Uptake of fatty acids and their mobilization from phospholipids in cultured monocyte-macrophages from rheumatoid arthritis patients. Source: Bomalaski, J S Goldstein, C S Dailey, A T Douglas, S D Zurier, R B ClinImmunol-Immunopathol. 1986 May; 39(2): 198-212 0090-1229
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Vitamin E and rheumatic diseases (osteoarthritis and rheumatoid arthritis). State of the art. Source: Biesalski, H. K. Frank, J. Bolten, W. Sangha, O. Nagel, E. Adam, O. AktuelleErnaehrungsmedizin (Germany). (1999). volume 24(1) page 29-36. 0341-0501
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Why do patients with rheumatoid arthritis use alternative treatments? Author(s): Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands.
[email protected] Source: Jacobs JWG Kraaimaat, F W Bijlsma, J W Clin-Rheumatol. 2001; 20(3): 192-6 0770-3198
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Yellow nail syndrome associated with thiol compound therapy for rheumatoid arthritis. Two case reports. Author(s): Rheumatology department, CHU Jean-Minjoz, Besancon, France. Source: Lehuede, G Toussirot, E Despaux, J Michel, F Wendling, D Joint-Bone-Spine. 2002 June; 69(4): 406-8 1297-319X
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to rheumatoid arthritis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Folic Acid Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Niacin Source: Integrative Medicine Communications; www.drkoop.com
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Niacin Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,892,00.html Pantothenic Acid Source: Healthnotes, Inc. www.healthnotes.com Pantothenic Acid Source: Integrative Medicine Communications; www.drkoop.com Pantothenic Acid and Pantethine Source: Prima Communications, Inc.www.personalhealthzone.com Pyridoxine Alternative names: Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Riboflavin Source: Integrative Medicine Communications; www.drkoop.com Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B3 (Niacin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B5 (Pantothenic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B6 (Pyridoxine) Alternative names: Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com
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Vitamin E Source: Healthnotes, Inc. www.healthnotes.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com •
Minerals Betaine Hydrochloride Source: Healthnotes, Inc. www.healthnotes.com Betaine Hydrochloride Source: Prima Communications, Inc.www.personalhealthzone.com Boron Source: Healthnotes, Inc. www.healthnotes.com Boron Source: Prima Communications, Inc.www.personalhealthzone.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Copper Source: Healthnotes, Inc. www.healthnotes.com Copper Source: Integrative Medicine Communications; www.drkoop.com Copper Source: Prima Communications, Inc.www.personalhealthzone.com Copper Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,886,00.html Creatine Monohydrate Source: Healthnotes, Inc. www.healthnotes.com Folate Source: Integrative Medicine Communications; www.drkoop.com Folate Alternative names: Vitamin B9 (Folic Acid) Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Iron Source: Healthnotes, Inc. www.healthnotes.com
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Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Manganese Source: Prima Communications, Inc.www.personalhealthzone.com Naproxen/Naproxen Sodium Source: Healthnotes, Inc. www.healthnotes.com Quercetin Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Healthnotes, Inc. www.healthnotes.com Selenium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Selenium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html Stinging Nettle Alternative names: Urtica dioica, Urtica urens, Nettle Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc. www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html
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•
Food and Diet Barley Source: Healthnotes, Inc. www.healthnotes.com Burdock Alternative names: Arctium lappa Source: Healthnotes, Inc. www.healthnotes.com Burdock Source: Prima Communications, Inc.www.personalhealthzone.com Burdock Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,235,00.html Cartilage Alternative names: Shark Cartilage Source: Integrative Medicine Communications; www.drkoop.com Cartilage Source: Prima Communications, Inc.www.personalhealthzone.com Coffee Source: Healthnotes, Inc. www.healthnotes.com Fasting Diet Source: Healthnotes, Inc. www.healthnotes.com Gluten-Free Diet Source: Healthnotes, Inc. www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-3 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-6 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1037,00.html Pain Source: Healthnotes, Inc. www.healthnotes.com
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Polyunsaturated Fats Source: Healthnotes, Inc. www.healthnotes.com Rye Source: Healthnotes, Inc. www.healthnotes.com Salmon Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,102,00.html Tendinitis Source: Healthnotes, Inc. www.healthnotes.com Vegetarian Diet Source: Healthnotes, Inc. www.healthnotes.com Wheat Source: Healthnotes, Inc. www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND RHEUMATOID ARTHRITIS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to rheumatoid arthritis. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to rheumatoid arthritis and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “rheumatoid arthritis” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to rheumatoid arthritis: •
A double blind observation for therapeutic effects of the tong luo kai bi tablets on rheumatoid arthritis. Author(s): Shi Y, Zhang H, Du X, Zhang M, Yin Y, Zhou C, Song S, Fu X, Li S, Liu Y, Li H, Li X, Wu X, Zhu Y. Source: J Tradit Chin Med. 1999 September; 19(3): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921143&dopt=Abstract
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A dual pathway model of daily stressor effects on rheumatoid arthritis. Author(s): Affleck G, Urrows S, Tennen H, Higgins P, Pav D, Aloisi R. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 1997 Spring; 19(2): 161-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9603691&dopt=Abstract
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A phase I study of ethyl acetate extract of the chinese antirheumatic herb Tripterygium wilfordii hook F in rheumatoid arthritis. Author(s): Tao X, Cush JJ, Garret M, Lipsky PE. Source: The Journal of Rheumatology. 2001 October; 28(10): 2160-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669150&dopt=Abstract
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A potential new treatment for rheumatoid arthritis: thunder god vine. Author(s): Lipsky PE, Tao XL. Source: Seminars in Arthritis and Rheumatism. 1997 April; 26(5): 713-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9144848&dopt=Abstract
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A randomized controlled trial of homeopathy in rheumatoid arthritis. Author(s): Fisher P, Scott DL. Source: Rheumatology (Oxford, England). 2001 September; 40(9): 1052-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561118&dopt=Abstract
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A randomized double blind, placebo controlled trial of topical Tripterygium wilfordii in rheumatoid arthritis: reanalysis using logistic regression analysis. Author(s): Cibere J, Deng Z, Lin Y, Ou R, He Y, Wang Z, Thorne A, Lehman AJ, Tsang IK, Esdaile JM. Source: The Journal of Rheumatology. 2003 March; 30(3): 465-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610802&dopt=Abstract
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A study of the effects of pulsed electromagnetic field therapy with respect to serological grouping in rheumatoid arthritis. Author(s): Ganguly KS, Sarkar AK, Datta AK, Rakshit A. Source: J Indian Med Assoc. 1998 September; 96(9): 272-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10063282&dopt=Abstract
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A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Author(s): Hafstrom I, Ringertz B, Spangberg A, von Zweigbergk L, Brannemark S, Nylander I, Ronnelid J, Laasonen L, Klareskog L. Source: Rheumatology (Oxford, England). 2001 October; 40(10): 1175-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600749&dopt=Abstract
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Abnormal fatty acid pattern in rheumatoid arthritis. A rationale for treatment with marine and botanical lipids. Author(s): Navarro E, Esteve M, Olive A, Klaassen J, Cabre E, Tena X, FernandezBanares F, Pastor C, Gassull MA. Source: The Journal of Rheumatology. 2000 February; 27(2): 298-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10685788&dopt=Abstract
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Acupuncture and other alternative therapies in rheumatoid arthritis. Author(s): Hardware B, Lacey A. Source: Prof Nurse. 2002 March; 17(7): 437-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917436&dopt=Abstract
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Acupuncture and rheumatoid arthritis. Author(s): Tukmachi E. Source: Rheumatology (Oxford, England). 2000 October; 39(10): 1153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11035139&dopt=Abstract
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Advances in TCM symptomatology of rheumatoid arthritis. Author(s): Li S. Source: J Tradit Chin Med. 2002 June; 22(2): 137-42. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125492&dopt=Abstract
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Alternative treatments for rheumatoid arthritis. Author(s): Gaby AR. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1999 December; 4(6): 392-402. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608912&dopt=Abstract
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An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Author(s): Skoldstam L, Hagfors L, Johansson G. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 208-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594104&dopt=Abstract
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An historical review of rheumatoid arthritis treatment: 1948 to 1952. Author(s): Karsh J, Hetenyi G Jr. Source: Seminars in Arthritis and Rheumatism. 1997 August; 27(1): 57-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9287391&dopt=Abstract
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Anti B cell therapy proves successful in severe cases of rheumatoid arthritis. Author(s): Marshall HE. Source: Trends in Immunology. 2001 January; 22(1): 13-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11286684&dopt=Abstract
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Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Author(s): Adam O, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W.
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Source: Rheumatology International. 2003 January; 23(1): 27-36. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548439&dopt=Abstract •
Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Author(s): Hagfors L, Leanderson P, Skoldstam L, Andersson J, Johansson G. Source: Nutrition Journal [electronic Resource]. 2003 July 30; 2(1): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952549&dopt=Abstract
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Antioxidant potential of two polyherbal. preparations used in Ayurveda for the treatment of rheumatoid arthritis. Author(s): Thabrew MI, Senaratna L, Samarawickrema N, Munasinghe C. Source: Journal of Ethnopharmacology. 2001 August; 76(3): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448551&dopt=Abstract
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Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders. Author(s): Darlington LG, Stone TW. Source: The British Journal of Nutrition. 2001 March; 85(3): 251-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11299072&dopt=Abstract
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B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Author(s): Shaw T, Quan J, Totoritis MC. Source: Annals of the Rheumatic Diseases. 2003 November; 62 Suppl 2: Ii55-Ii59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532151&dopt=Abstract
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Balneotherapy for rheumatoid arthritis and osteoarthritis. Author(s): Verhagen AP, de Vet HC, de Bie RA, Kessels AG, Boers M, Knipschild PG. Source: Cochrane Database Syst Rev. 2000; (2): Cd000518. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796385&dopt=Abstract
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Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP that suppresses tumor necrosis factor-alpha. Author(s): Kast RE. Source: International Immunopharmacology. 2001 November; 1(12): 2197-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11710548&dopt=Abstract
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Caring needs of patients with rheumatoid arthritis. Author(s): Nyman CS, Lutzen K.
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Source: Nursing Science Quarterly. 1999 April; 12(2): 164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847684&dopt=Abstract •
Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled trial. Leflunomide Rheumatoid Arthritis Investigators Group. Author(s): Tugwell P, Wells G, Strand V, Maetzel A, Bombardier C, Crawford B, Dorrier C, Thompson A. Source: Arthritis and Rheumatism. 2000 March; 43(3): 506-14. Erratum In: Arthritis Rheum 2000 June; 43(6): 1345. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10728742&dopt=Abstract
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Clinical observation on treatment of rheumatoid arthritis with fengshi xiandan in 53 cases. Author(s): Shen Y, Qu Q, Wang D. Source: J Tradit Chin Med. 2003 March; 23(1): 21-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747191&dopt=Abstract
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Cognitive, behavioral and physiological reactivity to pain as a predictor of long-term pain in rheumatoid arthritis patients. Author(s): Evers AW, Kraaimaat FW, van Riel PL, Bijlsma JW. Source: Pain. 2001 August; 93(2): 139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427325&dopt=Abstract
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Combination drug therapy in rheumatoid arthritis. Author(s): Russell AS, Ramos-Remus C. Source: The Journal of Rheumatology. 1997 April; 24(4): 803-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9101523&dopt=Abstract
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Computerized measurement of magnetic resonance imaging erosion volumes in patients with rheumatoid arthritis: a comparison with existing magnetic resonance imaging scoring systems and standard clinical outcome measures. Author(s): Bird P, Lassere M, Shnier R, Edmonds J. Source: Arthritis and Rheumatism. 2003 March; 48(3): 614-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632412&dopt=Abstract
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Considerations in the selection of an appropriate conditioning regimen for the treatment of rheumatoid arthritis by autologous peripheral blood stem cell transplantation. Author(s): Kashyap A, Snowden J.
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Source: J Rheumatol Suppl. 2001 October; 64: 39-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642503&dopt=Abstract •
Diet and rheumatoid arthritis--a review. Author(s): Mangge H, Hermann J, Schauenstein K. Source: Scandinavian Journal of Rheumatology. 1999; 28(4): 201-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10503555&dopt=Abstract
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Dietary n-3 fatty acids and therapy for rheumatoid arthritis. Author(s): James MJ, Cleland LG. Source: Seminars in Arthritis and Rheumatism. 1997 October; 27(2): 85-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9355207&dopt=Abstract
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Direct cost of rheumatoid arthritis during the first six years: a cost-of-illness study. Author(s): van Jaarsveld CH, Jacobs JW, Schrijvers AJ, Heurkens AH, Haanen HC, Bijlsma JW. Source: British Journal of Rheumatology. 1998 August; 37(8): 837-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9734674&dopt=Abstract
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Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients. Author(s): Andjelkovic Z, Vojinovic J, Pejnovic N, Popovic M, Dujic A, Mitrovic D, Pavlica L, Stefanovic D. Source: Clin Exp Rheumatol. 1999 July-August; 17(4): 453-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464556&dopt=Abstract
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Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis. Author(s): Agren JJ, Tvrzicka E, Nenonen MT, Helve T, Hanninen O. Source: The British Journal of Nutrition. 2001 February; 85(2): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11242480&dopt=Abstract
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Effect of bioresonance therapy on antioxidant system in lymphocytes in patients with rheumatoid arthritis. Author(s): Islamov BI, Balabanova RM, Funtikov VA, Gotovskii YV, Meizerov EE. Source: Bulletin of Experimental Biology and Medicine. 2002 September; 134(3): 248-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511993&dopt=Abstract
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Effect of cod liver oil on symptoms of rheumatoid arthritis. Author(s): Gruenwald J, Graubaum HJ, Harde A.
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Source: Adv Ther. 2002 March-April; 19(2): 101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069368&dopt=Abstract •
Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Author(s): van Ede AE, Laan RF, Rood MJ, Huizinga TW, van de Laar MA, van Denderen CJ, Westgeest TA, Romme TC, de Rooij DJ, Jacobs MJ, de Boo TM, van der Wilt GJ, Severens JL, Hartman M, Krabbe PF, Dijkmans BA, Breedveld FC, van de Putte LB. Source: Arthritis and Rheumatism. 2001 July; 44(7): 1515-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465701&dopt=Abstract
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Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. Author(s): McDougall J, Bruce B, Spiller G, Westerdahl J, McDougall M. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2002 February; 8(1): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890437&dopt=Abstract
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Effects of creatine supplementation on muscle weakness in patients with rheumatoid arthritis. Author(s): Willer B, Stucki G, Hoppeler H, Bruhlmann P, Krahenbuhl S. Source: Rheumatology (Oxford, England). 2000 March; 39(3): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10788538&dopt=Abstract
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Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis. Author(s): Venkatraman JT, Chu WC. Source: Journal of the American College of Nutrition. 1999 December; 18(6): 602-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613412&dopt=Abstract
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Effects of intercessory prayer on patients with rheumatoid arthritis. Author(s): Matthews DA, Marlowe SM, MacNutt FS. Source: Southern Medical Journal. 2000 December; 93(12): 1177-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11142453&dopt=Abstract
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Effects of paclitaxel on cultured synovial cells from patients with rheumatoid arthritis. Author(s): Kurose A, Yoshida W, Yoshida M, Sawai T. Source: Cytometry : the Journal of the Society for Analytical Cytology. 2001 August 1; 44(4): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11500851&dopt=Abstract
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Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis. Author(s): Volker D, Fitzgerald P, Major G, Garg M. Source: The Journal of Rheumatology. 2000 October; 27(10): 2343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11036827&dopt=Abstract
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Elastase from polymorphonuclear leukocyte in articular cartilage and synovial fluids of patients with rheumatoid arthritis. Author(s): Momohara S, Kashiwazaki S, Inoue K, Saito S, Nakagawa T. Source: Clinical Rheumatology. 1997 March; 16(2): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9093794&dopt=Abstract
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Electrical stimulation for the treatment of rheumatoid arthritis. Author(s): Brosseau LU, Pelland LU, Casimiro LY, Robinson VI, Tugwell PE, Wells GE. Source: Cochrane Database Syst Rev. 2002; (2): Cd003687. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076504&dopt=Abstract
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Elk velvet antler in rheumatoid arthritis: phase II trial. Author(s): Allen M, Oberle K, Grace M, Russell A. Source: Biological Research for Nursing. 2002 January; 3(3): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003439&dopt=Abstract
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Endocrine effects of the podophyllotoxine derivative drug CPH 82 (Reumacon) in patients with rheumatoid arthritis. Author(s): Carlstrom K, Hedin PJ, Jonsson L, Lerndal T, Lien J, Weitoft T, Axelson M. Source: Scandinavian Journal of Rheumatology. 2000; 29(2): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10777121&dopt=Abstract
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Examination of changes in interpersonal stress as a factor in disease exacerbations among women with rheumatoid arthritis. Author(s): Zautra AJ, Hoffman J, Potter P, Matt KS, Yocum D, Castro L. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 1997 Summer; 19(3): 279-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9603702&dopt=Abstract
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Expression, modulation and signalling of IL-17 receptor in fibroblast-like synoviocytes of patients with rheumatoid arthritis. Author(s): Kehlen A, Thiele K, Riemann D, Langner J. Source: Clinical and Experimental Immunology. 2002 March; 127(3): 539-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966773&dopt=Abstract
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Fasting followed by vegetarian diet in patients with rheumatoid arthritis: a systematic review. Author(s): Muller H, de Toledo FW, Resch KL.
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Source: Scandinavian Journal of Rheumatology. 2001; 30(1): 1-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11252685&dopt=Abstract •
Fish oil and rheumatoid arthritis: antiinflammatory and collateral health benefits. Author(s): Cleland LG, James MJ. Source: The Journal of Rheumatology. 2000 October; 27(10): 2305-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11036821&dopt=Abstract
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Fish oils are beneficial to patients with established rheumatoid arthritis. Author(s): Harrison RA, Harrison BJ. Source: The Journal of Rheumatology. 2001 November; 28(11): 2563-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708441&dopt=Abstract
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Fluorine-18-fluorodeoxyglucose uptake in rheumatoid arthritis-associated lung disease in a patient with thyroid cancer. Author(s): Bakheet SM, Powe J. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1998 February; 39(2): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9476924&dopt=Abstract
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Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposals for guidelines. Author(s): Endresen GK, Husby G. Source: Scandinavian Journal of Rheumatology. 2001; 30(3): 129-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469521&dopt=Abstract
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Folic acid and folinic acid supplementation during low-dose methotrexate therapy for rheumatoid arthritis: comment on the article by van Ede et al. Author(s): Morgan SL, Baggott JE, Alarcon GS, Koopman WJ. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1413-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115259&dopt=Abstract
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Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. Author(s): Morgan SL, Baggott JE, Lee JY, Alarcon GS. Source: The Journal of Rheumatology. 1998 March; 25(3): 441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9517760&dopt=Abstract
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Folic and folinic acid supplementation reduces methotrexate gastrointestinal side effects in rheumatoid arthritis. Author(s): Pincus T.
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Source: Clin Exp Rheumatol. 1998 November-December; 16(6): 667-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844757&dopt=Abstract •
Function and health-related quality of life: results from a randomized controlled trial of leflunomide versus methotrexate or placebo in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group. Author(s): Strand V, Tugwell P, Bombardier C, Maetzel A, Crawford B, Dorrier C, Thompson A, Wells G. Source: Arthritis and Rheumatism. 1999 September; 42(9): 1870-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10513801&dopt=Abstract
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Group education for patients with rheumatoid arthritis and their partners. Author(s): Riemsma RP, Taal E, Rasker JJ. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 556-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910564&dopt=Abstract
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Health-care use by rheumatoid arthritis patients compared with non-arthritic subjects. Author(s): Girard F, Guillemin F, Novella JL, Valckenaere I, Krzanowska K, Vitry F, Vittecoq O, Eschard JP, Blanchard F, Le Loet X. Source: Rheumatology (Oxford, England). 2002 February; 41(2): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886965&dopt=Abstract
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Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. Author(s): Soeken KL, Miller SA, Ernst E. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 652-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709541&dopt=Abstract
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Herbal therapy for treating rheumatoid arthritis. Author(s): Little C, Parsons T. Source: Cochrane Database Syst Rev. 2001; (1): Cd002948. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279784&dopt=Abstract
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Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients. Author(s): Erb N, Kitas GD. Source: Rheumatology (Oxford, England). 2001 June; 40(6): 715-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426040&dopt=Abstract
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Human fetal adrenal transplant: a possible role in relieving intractable pain in advanced rheumatoid arthritis.
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Author(s): Bhattacharya N, Chhetri MK, Mukherjee KL, Das SP, Mukherjee A, Bhattacharya M, Bhattacharya S. Source: Clin Exp Obstet Gynecol. 2002; 29(3): 197-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519043&dopt=Abstract •
Hyperhomocysteinemia in rheumatoid arthritis: influence of methotrexate treatment and folic acid supplementation. Author(s): Jensen OK, Rasmussen C, Mollerup F, Christensen PB, Hansen H, Ekelund S, Thulstrup AM. Source: The Journal of Rheumatology. 2002 August; 29(8): 1615-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180718&dopt=Abstract
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Identification of the pharmaceutical care issues of rheumatoid arthritis patients in secondary care. Author(s): O'Hare R, Muir A, Chapman S, Watson A, Hudson SA. Source: Pharmacy World & Science : Pws. 2001 October; 23(5): 183-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721675&dopt=Abstract
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Improvement in hand grip strength in normal volunteers and rheumatoid arthritis patients following yoga training. Author(s): Dash M, Telles S. Source: Indian J Physiol Pharmacol. 2001 July; 45(3): 355-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881576&dopt=Abstract
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Increased Ed-B fibronectin plasma levels in spondyloarthropathies: comparison with rheumatoid arthritis patients and a healthy population. Author(s): Claudepierre P, Allanore Y, Belec L, Larget-Piet B, Zardi L, Chevalier X. Source: Rheumatology (Oxford, England). 1999 November; 38(11): 1099-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10556262&dopt=Abstract
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Integration of stress research in rheumatoid arthritis: from Alexander to Zautra and back again. Author(s): Brady TJ. Source: Arthritis Care and Research : the Official Journal of the Arthritis Health Professions Association. 1998 April; 11(2): 77-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668729&dopt=Abstract
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Intercessory prayer and its effect on patients with rheumatoid arthritis. Author(s): Williams T. Source: Ky Nurse. 2002 January-March; 50(1): 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859558&dopt=Abstract
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Intermediate and late rheumatoid arthritis treated by tonifying the kidney, resolving phlegm and removing blood stasis. Author(s): Zhou X, Zhou Z, Jin M, Wang H, Wu M, Gu Q, Wang Z, Shang W. Source: J Tradit Chin Med. 2000 June; 20(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11038992&dopt=Abstract
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Juvenile rheumatoid arthritis: benefits from massage therapy. Author(s): Field T, Hernandez-Reif M, Seligman S, Krasnegor J, Sunshine W, RivasChacon R, Schanberg S, Kuhn C. Source: Journal of Pediatric Psychology. 1997 October; 22(5): 607-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383925&dopt=Abstract
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Leflunomide improves quality of life in rheumatoid arthritis. Author(s): Scott DL. Source: Scand J Rheumatol Suppl. 1999; 112: 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10668524&dopt=Abstract
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Leg ulceration in rheumatoid arthritis. Author(s): Grange M, Henderson C. Source: Nurs Times. 2001 June 14-20; 97(24): 63. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954493&dopt=Abstract
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Long-term efficacy of radon spa therapy in rheumatoid arthritis--a randomized, shamcontrolled study and follow-up. Author(s): Franke A, Reiner L, Pratzel HG, Franke T, Resch KL. Source: Rheumatology (Oxford, England). 2000 August; 39(8): 894-902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952746&dopt=Abstract
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Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations. Author(s): Morand EF, Leech M, Weedon H, Metz C, Bucala R, Smith MD. Source: Rheumatology (Oxford, England). 2002 May; 41(5): 558-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011381&dopt=Abstract
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Mediterranean diet intervention in rheumatoid arthritis. Author(s): Kjeldsen-Kragh J. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594101&dopt=Abstract
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Muscle relaxation training and quality of life in rheumatoid arthritis. A randomized controlled clinical trial. Author(s): Lundgren S, Stenstrom CH.
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n-3 fatty acid supplements in rheumatoid arthritis. Author(s): Kremer JM. Source: The American Journal of Clinical Nutrition. 2000 January; 71(1 Suppl): 349S-51S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617995&dopt=Abstract
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n-6 and n-3 essential fatty acids in rheumatoid arthritis and other rheumatic conditions. Author(s): Belch JJ, Muir A. Source: The Proceedings of the Nutrition Society. 1998 November; 57(4): 563-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10096117&dopt=Abstract
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Non-prescription complementary treatments used by rheumatoid arthritis patients attending a community-based rheumatology practice. Author(s): Buchbinder R, Gingold M, Hall S, Cohen M. Source: Internal Medicine Journal. 2002 May-June; 32(5-6): 208-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036218&dopt=Abstract
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Nutritional management of rheumatoid arthritis: a review of the evidence. Author(s): Rennie KL, Hughes J, Lang R, Jebb SA. Source: Journal of Human Nutrition and Dietetics : the Official Journal of the British Dietetic Association. 2003 April; 16(2): 97-109. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662368&dopt=Abstract
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Omega-3 fatty acids in rheumatoid arthritis: an overview. Author(s): Ariza-Ariza R, Mestanza-Peralta M, Cardiel MH. Source: Seminars in Arthritis and Rheumatism. 1998 June; 27(6): 366-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9662755&dopt=Abstract
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Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators. Author(s): Ostrakhovitch EA, Afanas'ev IB. Source: Biochemical Pharmacology. 2001 September 15; 62(6): 743-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11551519&dopt=Abstract
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Pain, coping and analgesic medication usage in rheumatoid arthritis patients. Author(s): Gustafsson M, Gaston-Johansson F, Aschenbrenner D, Merboth M.
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Peripheral beta-endorphin in rheumatoid arthritis. Author(s): Bender T, Barna I. Source: Scandinavian Journal of Rheumatology. 1998; 27(3): 236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9645422&dopt=Abstract
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Potentiated Antibodies to Tumor Necrosis Factor-alpha in the Therapy of Patients with Rheumatoid Arthritis. Author(s): Kozlovskaya LV, Mukhin NA, Rameev VV, Sarkisova IA, Epstein OI. Source: Bulletin of Experimental Biology and Medicine. 2003; 135 Suppl 1: 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949685&dopt=Abstract
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PPAR gamma ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice. Author(s): Shiojiri T, Wada K, Nakajima A, Katayama K, Shibuya A, Kudo C, Kadowaki T, Mayumi T, Yura Y, Kamisaki Y. Source: European Journal of Pharmacology. 2002 July 19; 448(2-3): 231-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144946&dopt=Abstract
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Practice variation in the treatment of rheumatoid arthritis among German rheumatologists. Author(s): Zink A, Listing J, Ziemer S, Zeidler H; German Collaborative Arthritis Centres. Source: The Journal of Rheumatology. 2001 October; 28(10): 2201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669156&dopt=Abstract
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Principles of rheumatoid arthritis control. Author(s): Palferman TG. Source: J Rheumatol Suppl. 2003 August; 67: 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926645&dopt=Abstract
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Principles of rheumatoid arthritis control. Author(s): Palferman TG. Source: The Journal of Rheumatology. 2003 August; 30(8): 10-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913895&dopt=Abstract
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Psychological interventions for rheumatoid arthritis: a meta-analysis of randomized controlled trials. Author(s): Astin JA, Beckner W, Soeken K, Hochberg MC, Berman B.
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Pulmonary nodule and aggressive tibialis posterior tenosynovitis in early rheumatoid arthritis. Author(s): Joosen H, Mellaerts B, Dereymaeker G, Westhovens R. Source: Clinical Rheumatology. 2000; 19(5): 392-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11055831&dopt=Abstract
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Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. Author(s): Chopra A, Lavin P, Patwardhan B, Chitre D. Source: The Journal of Rheumatology. 2000 June; 27(6): 1365-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852255&dopt=Abstract
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Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. Author(s): Mur E, Hartig F, Eibl G, Schirmer M. Source: The Journal of Rheumatology. 2002 April; 29(4): 678-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950006&dopt=Abstract
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Rapid improvement of osteomalacia by treatment in a case with Sjogren's syndrome, rheumatoid arthritis and renal tubular acidosis type 1. Author(s): Okada M, Suzuki K, Hidaka T, Shinohara T, Kataharada K, Matsumoto M, Takada K, Ohsuzu F. Source: Intern Med. 2001 August; 40(8): 829-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518137&dopt=Abstract
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Remission of rheumatoid arthritis with taxol in a patient with breast carcinoma. Author(s): Yoo WH, Baek HS. Source: The Journal of Rheumatology. 2000 June; 27(6): 1572-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852303&dopt=Abstract
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Renal involvement in Chinese patients with rheumatoid arthritis. Author(s): Ning-Sheng L. Source: Annals of the Rheumatic Diseases. 1998 September; 57(9): 571. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849318&dopt=Abstract
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Retrospective study of adverse events in patients with rheumatoid arthritis treated with second-line drugs. Author(s): Jiang L, Zhao N, Ni L.
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Source: Zhonghua Liu Xing Bing Xue Za Zhi. 2002 June; 23(3): 213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411093&dopt=Abstract •
Rheumatoid arthritis and the balance of dietary N-6 and N-3 essential fatty acids. Author(s): Cleland LG, James MJ. Source: British Journal of Rheumatology. 1997 May; 36(5): 513-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9189049&dopt=Abstract
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Rheumatoid arthritis and the older adult. Author(s): Ignatavicius DD. Source: Geriatric Nursing (New York, N.Y.). 2001 May-June; 22(3): 139-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410765&dopt=Abstract
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Rheumatoid arthritis treated with vegetarian diets. Author(s): Kjeldsen-Kragh J. Source: The American Journal of Clinical Nutrition. 1999 September; 70(3 Suppl): 594S600S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10479237&dopt=Abstract
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Rheumatoid arthritis: is the most effective treatment option a well kept secret? Author(s): Byrne J. Source: Aust Fam Physician. 2001 April; 30(4): 312. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355215&dopt=Abstract
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Rheumatoid arthritis: proposal for the use of anti-microbial therapy in early cases. Author(s): Ebringer A, Rashid T, Wilson C. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 2-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635939&dopt=Abstract
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Role of protein tyrosine kinase in IL-1 beta induced activation of mitogen-activated protein kinase in fibroblast-like synoviocytes of rheumatoid arthritis. Author(s): Lu H, Sun T, Yao L, Zhang Y. Source: Chin Med J (Engl). 2000 October; 113(10): 872-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775830&dopt=Abstract
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Roundtable I: Practice patterns for treating rheumatoid arthritis. Author(s): Abu-Samrah S, Bayham AG, Cluck RN, Gilliam M, Mahler DM, Seidenfeld J, Tamsky L, Vogenberg RF. Source: Am J Manag Care. 1999 September; 5(14 Suppl): S870-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10621073&dopt=Abstract
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Selenium supplementation in rheumatoid arthritis investigated in a double blind, placebo-controlled trial. Author(s): Peretz A, Siderova V, Neve J. Source: Scandinavian Journal of Rheumatology. 2001; 30(4): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578015&dopt=Abstract
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Serum levels of interleukin-6 and dehydroepiandrosterone sulphate in response to either fasting or a ketogenic diet in rheumatoid arthritis patients. Author(s): Fraser DA, Thoen J, Djoseland O, Forre O, Kjeldsen-Kragh J. Source: Clin Exp Rheumatol. 2000 May-June; 18(3): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895373&dopt=Abstract
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Sex hormone adjuvant therapy in rheumatoid arthritis. Author(s): Cutolo M. Source: Rheumatic Diseases Clinics of North America. 2000 November; 26(4): 881-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084949&dopt=Abstract
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Sleep quality in children with juvenile rheumatoid arthritis. Author(s): Labyak SE, Bourguignon C, Docherty S. Source: Holistic Nursing Practice. 2003 July-August; 17(4): 193-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889547&dopt=Abstract
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Spiritual healing as adjunct therapy for rheumatoid arthritis. Author(s): le Gallez P, Dimmock S, Bird HA. Source: British Journal of Nursing (Mark Allen Publishing). 2000Jun 8-21; 9(11): 695-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235261&dopt=Abstract
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Spirituality, resourcefulness, and arthritis impact on health perception of elders with rheumatoid arthritis. Author(s): Potter ML, Zauszniewski JA. Source: Journal of Holistic Nursing : Official Journal of the American Holistic Nurses' Association. 2000 December; 18(4): 311-31; Discussions 332-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847790&dopt=Abstract
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Stress and rheumatoid arthritis: an integrative review. Author(s): Huyser B, Parker JC. Source: Arthritis Care and Research : the Official Journal of the Arthritis Health Professions Association. 1998 April; 11(2): 135-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668736&dopt=Abstract
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Substance use among adolescents with juvenile rheumatoid arthritis. Author(s): Nash AA, Britto MT, Lovell DJ, Passo MH, Rosenthal SL.
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TCM treatment for 40 cases of rheumatoid arthritis with channel blockage due to yin deficiency. Author(s): Yang W, Ouyang J, Zhu K, Zhou S, Peng Z. Source: J Tradit Chin Med. 2003 September; 23(3): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535175&dopt=Abstract
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The costs of treating rheumatoid arthritis patients with complementary medicine: exploring the issue. Author(s): van Haselen RA, Graves N, Dahiha S. Source: Complementary Therapies in Medicine. 1999 December; 7(4): 217-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10709304&dopt=Abstract
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The effect of acupuncture on patients with rheumatoid arthritis: a randomized, placebo-controlled cross-over study. Author(s): David J, Townsend S, Sathanathan R, Kriss S, Dore CJ. Source: Rheumatology (Oxford, England). 1999 September; 38(9): 864-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10515648&dopt=Abstract
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The importance of enhancing self-efficacy in rheumatoid arthritis. Author(s): Smarr KL, Parker JC, Wright GE, Stucky-Ropp RC, Buckelew SP, Hoffman RW, O'Sullivan FX, Hewett JE. Source: Arthritis Care and Research : the Official Journal of the Arthritis Health Professions Association. 1997 February; 10(1): 18-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9313386&dopt=Abstract
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The relationships of cognitive coping and pain control beliefs to pain and adjustment among African-American and Caucasian women with rheumatoid arthritis. Author(s): Jordan MS, Lumley MA, Leisen JC. Source: Arthritis Care and Research : the Official Journal of the Arthritis Health Professions Association. 1998 April; 11(2): 80-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668730&dopt=Abstract
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The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Author(s): Dorner T, Burmester GR. Source: Current Opinion in Rheumatology. 2003 May; 15(3): 246-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707577&dopt=Abstract
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The role of complementary and alternative therapies in managing rheumatoid arthritis. Author(s): Taibi DM, Bourguignon C. Source: Family & Community Health. 2003 January-March; 26(1): 41-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802127&dopt=Abstract
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The role of fish oils in the treatment of rheumatoid arthritis. Author(s): Cleland LG, James MJ, Proudman SM. Source: Drugs. 2003; 63(9): 845-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678571&dopt=Abstract
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The role of nutrition and diet in rheumatoid arthritis. Author(s): Martin RH. Source: The Proceedings of the Nutrition Society. 1998 May; 57(2): 231-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9656325&dopt=Abstract
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The treatment of rheumatoid arthritis in this century: from spas to monoclonal antibodies. Author(s): Pasero G. Source: Clin Exp Rheumatol. 1997 May-June; 15 Suppl 17: S67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266135&dopt=Abstract
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The use of homeopathic preparation vozraston in the therapy of patients with rheumatoid arthritis. Author(s): Noskov SM, Snigireva AV, Dolgova LN, Somova MA, Polyakov DP. Source: Bulletin of Experimental Biology and Medicine. 2003; 135 Suppl 1: 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949664&dopt=Abstract
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The use of self-management strategies by people with rheumatoid arthritis. Author(s): Hammond A. Source: Clinical Rehabilitation. 1998 February; 12(1): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9549029&dopt=Abstract
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The water-soluble fraction of bee venom produces antinociceptive and antiinflammatory effects on rheumatoid arthritis in rats. Author(s): Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ, Lee JH. Source: Life Sciences. 2002 May 31; 71(2): 191-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031688&dopt=Abstract
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Therapeutic effect of needle warming through moxibustion at twelve shu points on rheumatoid arthritis. Author(s): Li C, Jiang Z, Li Y.
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Therapeutic effects of the instant rheumatoid medicinal granules for treatment of acute rheumatoid arthritis--a report of 34 cases. Author(s): Kou Q, Fang D. Source: J Tradit Chin Med. 1997 September; 17(3): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437187&dopt=Abstract
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Thermotherapy for treating rheumatoid arthritis. Author(s): Robinson V, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P. Source: Cochrane Database Syst Rev. 2002; (2): Cd002826. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076454&dopt=Abstract
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Thermotherapy for treating rheumatoid arthritis. Author(s): Robinson V, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P. Source: Cochrane Database Syst Rev. 2002; (1): Cd002826. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869637&dopt=Abstract
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Thermotherapy for treating rheumatoid arthritis. Author(s): Welch V, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P. Source: Cochrane Database Syst Rev. 2001; (2): Cd002826. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406046&dopt=Abstract
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Thermotherapy for treating rheumatoid arthritis. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12137622
Author(s): Cochrane Database Syst Rev. 2002;(3):CD001283 Source: Cochrane Database Syst Rev. 2000; (4): Cd002826. Review. Update In: <Title>Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand. Author(s): Brosseau L, Yonge KA, Robinson V, Marchand S, Judd M, Wells G, Tugwell P. Source: Cochrane Database Syst Rev. 2003; (3): Cd004287. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918009&dopt=Abstract
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Treatment of rheumatoid arthritis with a peptide diet: a randomized, controlled trial. Author(s): Holst-Jensen SE, Pfeiffer-Jensen M, Monsrud M, Tarp U, Buus A, Hessov I, Thorling E, Stengaard-Pedersen K. Source: Scandinavian Journal of Rheumatology. 1998; 27(5): 329-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808394&dopt=Abstract
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Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points--a randomized double blind clinical study. Author(s): Usichenko TI, Ivashkivsky OI, Gizhko VV. Source: Acupuncture & Electro-Therapeutics Research. 2003; 28(1-2): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934956&dopt=Abstract
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Two configurations of static magnetic fields for treating rheumatoid arthritis of the knee: a double-blind clinical trial. Author(s): Segal NA, Toda Y, Huston J, Saeki Y, Shimizu M, Fuchs H, Shimaoka Y, Holcomb R, McLean MJ. Source: Archives of Physical Medicine and Rehabilitation. 2001 October; 82(10): 1453-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588753&dopt=Abstract
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Uncooked, lactobacilli-rich, vegan food and rheumatoid arthritis. Author(s): Nenonen MT, Helve TA, Rauma AL, Hanninen OO. Source: British Journal of Rheumatology. 1998 March; 37(3): 274-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566667&dopt=Abstract
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Use of alternative drug therapies by patients with rheumatoid arthritis in Korea. Author(s): Ji JD, Chun BC, Song GG. Source: The Journal of Rheumatology. 2000 June; 27(6): 1573-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852304&dopt=Abstract
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Using nurse case management to promote self-efficacy in individuals with rheumatoid arthritis. Author(s): Barry J, McQuade C, Livingstone T. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 1998 November-December; 23(6): 300-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10223032&dopt=Abstract
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Utilization characteristics of health care service for rheumatoid arthritis patients in Korea. Author(s): Cho KJ, Jang SH, Lee SK, Doh WS. Source: Yonsei Medical Journal. 1998 June; 39(3): 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664830&dopt=Abstract
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Why do patients with rheumatoid arthritis use alternative treatments? Author(s): Jacobs JWG, Kraaimaat FW, Bijlsma JW. Source: Clinical Rheumatology. 2001; 20(3): 192-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434472&dopt=Abstract
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to rheumatoid arthritis; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Allergies and Sensitivities Source: Healthnotes, Inc. www.healthnotes.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Bursitis Source: Healthnotes, Inc. www.healthnotes.com Bursitis Source: Integrative Medicine Communications; www.drkoop.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com
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Indigestion, Heartburn, and Low Stomach Acidity Source: Healthnotes, Inc. www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc. www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Raynaud's Phenomenon Source: Integrative Medicine Communications; www.drkoop.com Restless Legs Syndrome Source: Healthnotes, Inc. www.healthnotes.com Rheumatoid Arthritis Source: Healthnotes, Inc. www.healthnotes.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc. www.healthnotes.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Chiropractic Source: Healthnotes, Inc. www.healthnotes.com Chiropractic Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,681,00.html Feldenkrais Source: WholeHealthMD.com, LLC. www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,695,00.html Hellerwork Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,700,00.html Homeopathy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,703,00.html Massage Source: Integrative Medicine Communications; www.drkoop.com Naturopathy Source: Integrative Medicine Communications; www.drkoop.com Nutrition Source: Integrative Medicine Communications; www.drkoop.com Rolfing Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,732,00.html Trager approach Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,741,00.html Writing therapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,745,00.html •
Chinese Medicine Chuanwu Alternative names: Common Monkshood Mother Root; Radix Aconiti Source: Chinese Materia Medica Goupi Gao Alternative names: Goupi Plaster Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Goupi%20Gao&mh=10&sb=--&view_records=View+Records
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Guogong Jiu Alternative names: Guogong Wine Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Guogong%20Jiu&mh=10&sb= ---&view_records=View+Records Haifengteng Alternative names: Kadsura Pepper Stem; Caulis Piperis Kadsurae Source: Chinese Materia Medica Jinqian Baihuashe Alternative names: Coin-like White-banded Snake; Jinqian Baihuashe (Jin Qian Bai Hua She); Bungarus Parvus Source: Chinese Materia Medica Liangtoujian Alternative names: Radde Anemone Rhizome; Rhizoma Ahemones Daddeanae Source: Chinese Materia Medica Mugua Wan Alternative names: Mugua Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Mugua%20Wan&mh=10&sb=--&view_records=View+Records Qiannianjian Alternative names: Obscured Homalomena Rhizome; Rhizoma Homalomenae Source: Chinese Materia Medica Qishe Alternative names: Long-noded Pit Viper; Qishe (Qi She); Agkistrodon Source: Chinese Materia Medica Qufeng Shujin Wan Alternative names: Qufeng Shujin Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Qufeng%20Shujin%20Wan&m h=10&sb=---&view_records=View+Records Shujin Huoluo Jiu Alternative names: Shujin Huoluo Wine; Shujin Huoluo Jiu
(Shu Jin Huo Luo Jiu) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China
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Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Shujin%20Huoluo%20Jiu&mh =10&sb=---&view_records=View+Records Shujin Wan Alternative names: Qufeng Shujin Pills; Qufeng Shujin Wan Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Hyperlink: http://www.newcenturynutrition.com/cgilocal/patent_herbs_db/db.cgi?db=default&Chinese=Shujin%20Wan&mh=10&sb=--&view_records=View+Records •
Homeopathy Arnica Source: Healthnotes, Inc. www.healthnotes.com Aurum metallicum Source: Healthnotes, Inc. www.healthnotes.com Bryonia Source: Healthnotes, Inc. www.healthnotes.com Calcarea carbonica Source: Healthnotes, Inc. www.healthnotes.com Calcarea fluorica Source: Healthnotes, Inc. www.healthnotes.com Causticum Source: Healthnotes, Inc. www.healthnotes.com Dulcamara Source: Healthnotes, Inc. www.healthnotes.com Kali bichromicum Source: Healthnotes, Inc. www.healthnotes.com Kali carbonicum Source: Healthnotes, Inc. www.healthnotes.com Kalmia latifolia Source: Healthnotes, Inc. www.healthnotes.com Ledum palustre Source: Healthnotes, Inc. www.healthnotes.com Pulsatilla Source: Healthnotes, Inc. www.healthnotes.com Rhododendron Source: Healthnotes, Inc. www.healthnotes.com
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Ruta graveolens Source: Healthnotes, Inc. www.healthnotes.com •
Herbs and Supplements Adrenal Extract Source: Healthnotes, Inc. www.healthnotes.com ALA Source: Integrative Medicine Communications; www.drkoop.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com Amino Acids Overview Source: Healthnotes, Inc. www.healthnotes.com Ananas comosus Source: Integrative Medicine Communications; www.drkoop.com Antimalarial Drugs Source: Healthnotes, Inc. www.healthnotes.com Arginine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10005,00.html Aspirin Source: Healthnotes, Inc. www.healthnotes.com Azathioprine Source: Healthnotes, Inc. www.healthnotes.com Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com BLACK COHOSH Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca BLADDERWRACK Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Boswellia Alternative names: Frankincense; Boswellia serrata Roxb. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
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Boswellia Alternative names: Boswellia serrata Source: Healthnotes, Inc. www.healthnotes.com Boswellia Source: Prima Communications, Inc.www.personalhealthzone.com Boswellia Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,759,00.html Bromelain Source: Healthnotes, Inc. www.healthnotes.com Bromelain Alternative names: Ananas comosus, Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Bromelain Source: Prima Communications, Inc.www.personalhealthzone.com Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Cat’s Claw Alternative names: Uncaria tomentosa Source: Healthnotes, Inc. www.healthnotes.com Cat's Claw Source: Prima Communications, Inc.www.personalhealthzone.com Cayenne Alternative names: Capsicum annuum, Capsicum frutescens Source: Healthnotes, Inc. www.healthnotes.com Celecoxib Source: Healthnotes, Inc. www.healthnotes.com Celery Seed Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Cetyl Myristoleate Source: Healthnotes, Inc. www.healthnotes.com
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Chaparral Alternative names: Larrea tridentata Source: Healthnotes, Inc. www.healthnotes.com Chemotherapy Source: Healthnotes, Inc. www.healthnotes.com Cholecalciferol Source: Integrative Medicine Communications; www.drkoop.com Chrysanthemum parthenium Source: Integrative Medicine Communications; www.drkoop.com Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc. www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com Devil’s Claw Alternative names: Harpagophytum procumbens Source: Healthnotes, Inc. www.healthnotes.com Devil's Claw Source: Prima Communications, Inc.www.personalhealthzone.com DHEA Source: Integrative Medicine Communications; www.drkoop.com Diclofenac Source: Healthnotes, Inc. www.healthnotes.com Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com DMSO Source: Healthnotes, Inc. www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc. www.healthnotes.com Echinacea Source: Prima Communications, Inc.www.personalhealthzone.com Echinacea Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html
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Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com EPA Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Etodolac Source: Healthnotes, Inc. www.healthnotes.com Eucalyptus Alternative names: Eucalyptus globulus Source: Healthnotes, Inc. www.healthnotes.com Evening Primrose Alternative names: Oenothera biennis, Sun Drop Source: Integrative Medicine Communications; www.drkoop.com Feverfew Alternative names: Tanacetum parthenium, Chrysanthemum parthenium Source: Integrative Medicine Communications; www.drkoop.com Feverfew Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,780,00.html Flavonoids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Flurbiprofen Source: Healthnotes, Inc. www.healthnotes.com Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc. www.healthnotes.com Ginger Source: Prima Communications, Inc.www.personalhealthzone.com Ginger Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,787,00.html
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GLA Source: Integrative Medicine Communications; www.drkoop.com GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glucosamine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,790,00.html Glutamine Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Green-Lipped Mussel Source: Healthnotes, Inc. www.healthnotes.com Histidine Source: Healthnotes, Inc. www.healthnotes.com Histidine Source: Prima Communications, Inc.www.personalhealthzone.com Horsetail Source: Prima Communications, Inc.www.personalhealthzone.com Hydroxychloroquine Source: Healthnotes, Inc. www.healthnotes.com Ibuprofen Source: Healthnotes, Inc. www.healthnotes.com Indomethacin Source: Healthnotes, Inc. www.healthnotes.com Inhalant, Systemic, and Topical Corticosteroids Source: Integrative Medicine Communications; www.drkoop.com Ketoprofen Source: Healthnotes, Inc. www.healthnotes.com Lipase Source: Integrative Medicine Communications; www.drkoop.com Meadowsweet Alternative names: Filipendula ulmaria Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com
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Methotrexate Source: Healthnotes, Inc. www.healthnotes.com Methotrexate Alternative names: Rheumatrex Source: Prima Communications, Inc.www.personalhealthzone.com MSM Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,807,00.html Nabumetone Source: Healthnotes, Inc. www.healthnotes.com Nettle Alternative names: Urtica dioica Source: Healthnotes, Inc. www.healthnotes.com Nettle Source: Integrative Medicine Communications; www.drkoop.com Non-steroidal Anti-Inflammatory Drugs Source: Healthnotes, Inc. www.healthnotes.com Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Source: Integrative Medicine Communications; www.drkoop.com Oenothera biennis Source: Integrative Medicine Communications; www.drkoop.com Oral Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com Oxaprozin Source: Healthnotes, Inc. www.healthnotes.com PABA Source: Healthnotes, Inc. www.healthnotes.com Penicillamine Source: Healthnotes, Inc. www.healthnotes.com Penicillamine Alternative names: Cuprimine, Depen Source: Prima Communications, Inc.www.personalhealthzone.com Phenylalanine Source: Healthnotes, Inc. www.healthnotes.com
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Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Picrorhiza Alternative names: Picrorhiza kurroa Source: Healthnotes, Inc. www.healthnotes.com Piroxicam Source: Healthnotes, Inc. www.healthnotes.com Pollen Source: Healthnotes, Inc. www.healthnotes.com Pregnenolone Source: Healthnotes, Inc. www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Proteolytic Enzymes Source: Prima Communications, Inc.www.personalhealthzone.com Rosemary Alternative names: Rosmarinus officinalis Source: Healthnotes, Inc. www.healthnotes.com Salsalate Source: Healthnotes, Inc. www.healthnotes.com Sarsaparilla Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Shark Cartilage Source: Integrative Medicine Communications; www.drkoop.com Sulfasalazine Source: Healthnotes, Inc. www.healthnotes.com Sulindac Source: Healthnotes, Inc. www.healthnotes.com Sun Drop Source: Integrative Medicine Communications; www.drkoop.com Tanacetum parthenium Source: Integrative Medicine Communications; www.drkoop.com
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Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc. www.healthnotes.com Turmeric Source: Prima Communications, Inc.www.personalhealthzone.com Turmeric Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10062,00.html Urtica dioica Source: Integrative Medicine Communications; www.drkoop.com Urtica urens Source: Integrative Medicine Communications; www.drkoop.com White Willow Source: Prima Communications, Inc.www.personalhealthzone.com Wild Yam Alternative names: Dioscorea villosa Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Willow Alternative names: Salix alba Source: Healthnotes, Inc. www.healthnotes.com Willow Bark Alternative names: There are several species of willow includingSalix alba, Salix nigra, Salix fragilis, Salix purpurea, Salix babylonica, White Willow, European Willow, Black Willow, Pussy Willow, Crack Willow, Purple Willow, Weeping Willow, Liu-zhi Source: Integrative Medicine Communications; www.drkoop.com Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Yucca Alternative names: Yucca schidigera , Yucca spp. Source: Healthnotes, Inc. www.healthnotes.com Yucca Source: Prima Communications, Inc.www.personalhealthzone.com
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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON RHEUMATOID ARTHRITIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to rheumatoid arthritis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “rheumatoid arthritis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on rheumatoid arthritis, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Rheumatoid Arthritis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to rheumatoid arthritis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Comparison of the Effects of Isometric and Isokinetic Training on Muscle Fibre Size and Strength in Women with Rheumatoid Arthritis by Wessel, Jean; Phd from University of Alberta (canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK63989
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A Cross-cultural Comparison of Pain Description in Children with Polyarticular Juvenile Rheumatoid Arthritis in the United States and in Egypt by Von Weiss, Renee Terese; Phd from University of Kansas, 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/3083203
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A Psychosocial Model for the Impact of Rheumatoid Arthritis on Well-being by Wilkins, Kendra E. Phd from Wayne State University, 1999, 162 pages http://wwwlib.umi.com/dissertations/fullcit/9954575
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An Investigation of Oral History Narrative and Content Analysis Technique for Community Field Work in Rehabilitation Focusing upon Females with Rheumatoid Arthritis by Sirmons, Martha Ruddon, Edd from Auburn University, 1985, 166 pages http://wwwlib.umi.com/dissertations/fullcit/8518414
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Correlates of Health Perceptions among Individuals with Rheumatoid Arthritis by Guccione, Andrew Anthony, Phd from Boston University, 1988, 174 pages http://wwwlib.umi.com/dissertations/fullcit/8813637
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Determinants of Physical Activity in Older Women with Rheumatoid Arthritis by Semanik, Pamela A. Phd from University of Illinois at Chicago, Health Sciences Center, 2002, 204 pages http://wwwlib.umi.com/dissertations/fullcit/3058240
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Development of a Measure of Investigativeness, and Its Role in Women's Adaptation to Rheumatoid Arthritis by Vagi, Anne Barbara; Phd from University of Waterloo (canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK66425
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Economic Approaches to the Problem of Acceptable Clinical Risks: the Case of Prescription Drugs and Chronic Rheumatic Disease (clinical Risk, Rheumatoid Arthritis) by O'brien, Bernie J., Phd from Brunel University (united Kingdom), 1990, 385 pages http://wwwlib.umi.com/dissertations/fullcit/DX92575
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Exploring the Lived Experience of Female Adolescents with Juvenile Rheumatoid Arthritis: a Model of Human Occupation Perspective by Tommasulo, Jeanmarie F. Ms from D'youville College, 2002, 109 pages http://wwwlib.umi.com/dissertations/fullcit/1409942
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Exploring the Lived Experience of Women with Rheumatoid Arthritis: a Model of Human Occupation Perspective by Gee, Bryan Mark; Ms from D'youville College, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/1409937
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Family Adaptability, Cohesion and Conflict in Families with Rheumatoid Arthritis, Chronic Pain and Depression by Caldwell, Karen Leigh, Phd from Virginia Polytechnic Institute and State University, 1988, 106 pages http://wwwlib.umi.com/dissertations/fullcit/8910943
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From Social Theory to Social Policy: Social Class and the Epidemiology of Disability: a Case Study among Persons with Rheumatoid Arthritis. by Yelin, Edward Harris, Phd from University of California, Berkeley, 1979, 280 pages http://wwwlib.umi.com/dissertations/fullcit/8000583
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Gender, Class and the Illness Experience of Rheumatoid Arthritis by Fifield, Judith Anne, Phd from The University of Connecticut, 1990, 158 pages http://wwwlib.umi.com/dissertations/fullcit/9110414
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Gold in Rheumatoid Arthritis : Its Effect on Plasma Cortisol and Its Deposition in Skin by Jeffery, Dorothy A; Phd from University of Alberta (canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK21856
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Holistic Fatherhood: a Grounded Theory Approach to Understanding Fathers of Children with Juvenile Rheumatoid Arthritis (jra) by Mcneill, Harold Edwin (ted); Phd from University of Toronto (canada), 2001, 312 pages http://wwwlib.umi.com/dissertations/fullcit/NQ63799
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Impact of Anti-inflammatory Medications, Methotrexate, and Steroidal Medications on Psychosocial Functioning and Medical Status in Juvenile Rheumatoid Arthritis Patients by Ryser, Christina Nicole; Phd from The University of Texas Southwestern Medical Center at Dallas, 2002 http://wwwlib.umi.com/dissertations/fullcit/f865233
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Interpersonal Expectations and Psychosocial Adjustment to Chronic Illness: Reducing Discrepancies among Persons with Rheumatoid Arthritis by Thompson, Shawn Norvell; Phd from State University of New York at Stony Brook, 2002, 87 pages http://wwwlib.umi.com/dissertations/fullcit/3067559
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Juvenile Rheumatoid Arthritis: a Psychosocial Assessment of Adolescent Females and Their Mothers (pediatric Chronic Illness, Coping Models, Family Systems) by Baird, Sally Felgenhauer, Phd from University of Washington, 1986, 141 pages http://wwwlib.umi.com/dissertations/fullcit/8613135
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Juvenile Rheumatoid Arthritis: Implications for Nursing Education (childhood Illness) by Dressler, Mary Buckley, Edd from Temple University, 1992, 158 pages http://wwwlib.umi.com/dissertations/fullcit/9227454
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Life Stress and Emotional Regulation Strategies during a Personal Disclosure Task: Health Implications for Patients with Rheumatoid Arthritis by Meyer, Tina Marie; Phd from Wayne State University, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3086453
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Lymphocytes and Rheumatoid Arthritis by Mandeville, Robert Parnell; Phd from Memorial University of Newfoundland (canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK46760
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Nutritional Status of Postmenopausal Women with and without Rheumatoid Arthritis by Woolf, Kathleen; Phd from Arizona State University, 2002, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3057423
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Pain Measurement in Rheumatoid Arthritis: Applications of a Behavioral Approach (arthritis) by Buescher, Keith Lee, Phd from University of Missouri - Columbia, 1989, 178 pages http://wwwlib.umi.com/dissertations/fullcit/9010541
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Piroxicam in Healthy Adults and Rheumatoid Arthritis Patients Disposition Kinetics and Clinical Effects by Richardson, Corrie Jane; Phd from The University of Saskatchewan (canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL29256
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Relationships between Coping Beliefs, Coping Practices, and Coping Resources and the Quality of Life in Rheumatoid Arthritis Patients (arthritis) by Strong, Thomas Irvin, Phd from University of Alberta (canada), 1990, 243 pages http://wwwlib.umi.com/dissertations/fullcit/NN64859
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Social and Psychological Well-being, Pain, Functional Ability, and Choice of Coping Strategies in Patients with Rheumatoid Arthritis (counseling, Health) by Morgan, Cynthia Gray, Phd from University of California, Los Angeles, 1985, 362 pages http://wwwlib.umi.com/dissertations/fullcit/8603974
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Socio-psychological Factors in Rheumatoid Arthritis by Steffenhagen, Ronald Albert, Phd from State University of New York at Buffalo, 1966, 142 pages http://wwwlib.umi.com/dissertations/fullcit/6607988
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The Effect of an Individualized Instruction Program on the Education of Outpatients with Rheumatoid Arthritis by Neuberger, Geri Budesheim, Edd from University of Kansas, 1983, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8403597
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The Effects of Expressive Release Therapy upon the Physical and Psychological Wellbeing of Rheumatoid Arthritis Patients by Engle, David Eugene, Phd from The University of Arizona, 1985, 178 pages http://wwwlib.umi.com/dissertations/fullcit/8517495
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The Effects of Music and Music Vibration Using the Mvt(tm) on the Relief of Rheumatoid Arthritis Pain by Chesky, Kris S., Phd from University of North Texas, 1992, 142 pages http://wwwlib.umi.com/dissertations/fullcit/9300593
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The Experience of Rheumatoid Arthritis by Hovanec, Margret Anne, Phd from University of Toronto (canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/f468806
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The Experience of Rheumatoid Arthritis by Hovanec, Margret; Phd from University of Toronto (canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK50276
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The Functional Characterization of in Vivo Activated Interleukin-2 Responsive T Cells in Rheumatoid Arthritis by Cell Cloning Techniques by Ofosu-appiah, William A; Phd from The University of Manitoba (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL47924
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The Relationship between Pain Responsiveness and Disease Activity in Fibrositis and Rheumatoid Arthritis by Scudds, Roger A; Phd from The University of Western Ontario (canada), 1990 http://wwwlib.umi.com/dissertations/fullcit/NL55283
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The Role of Inflammatory Cytokines in Rheumatoid Arthritis: Comparison to Allergic Diseases by Schuerwegh, Annemie Johanna; Phd from Universitaire Instelling Antwerpen (belgium), 2002, 214 pages http://wwwlib.umi.com/dissertations/fullcit/3066152
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Variations in Compliance with Medical Regimens and Utilization of Medical Services among Patients with Rheumatoid Arthritis by Kasteler, Josephine Mix, Phd from The University of Utah, 1970, 140 pages http://wwwlib.umi.com/dissertations/fullcit/7023079
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Why Does Formal Education Predict Mortality? an Evaluation of Mediational Processes (rheumatoid Arthritis, Education Level, Learned Helplessness) by Callahan, Leigh Fleming, Phd from Vanderbilt University, 1992, 150 pages http://wwwlib.umi.com/dissertations/fullcit/9315805
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Women with Rheumatoid Arthritis: a Qualitative Investigation of Personality and Coping Methods (arthritis) by Thompson, Linda V., Phd from Arizona State University, 1993, 245 pages http://wwwlib.umi.com/dissertations/fullcit/9320665
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Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. ARTHRITIS
CLINICAL
TRIALS
AND
RHEUMATOID
Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning rheumatoid arthritis.
Recent Trials on Rheumatoid Arthritis The following is a list of recent trials dedicated to rheumatoid arthritis.8 Further information on a trial is available at the Web site indicated. •
A Multicenter Study of the Safety of Human Anti-TNF Monoclonal Antibody D2E7 in Subjects with Active Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): Abbott Laboratories Purpose - Excerpt: Purpose of the study is to evaluate safety by collecting serious adverse events in subjects with moderately to severely active rheumatoid arthritis who are unable to obtain etanercept and who have failed one or more prior DMARDs. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049751
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy, and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Children With Polyarticular Juvenile Rheumatoid Arthritis Condition(s): Arthritis, Juvenile Rheumatoid
8
These are listed at www.ClinicalTrials.gov.
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Study Status: This study is currently recruiting patients. Sponsor(s): Abbott Laboratories Purpose - Excerpt: This is a multicenter, Phase III randomized, placebo-controlled study in which polyarticular JRA subjects who are either MTX treated or non-MTX treated will initially receive Adalimumab by subcutaneous injection every other week for a fourmonth open-label lead-in period. Subjects who respond to the open-label therapy will then be rolled over into the double-blind portion of the study and will be randomized to receive either adalimumab or placebo for an additional 32 weeks or until flare of disease, whichever is earlier. Subjects who experience disease flare during the double-blind portion of the study or subjects who complete 48 weeks of the study will be given the option to receive open-label treatment with adalimumab for an additional 44 weeks. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048542 •
A Phase 2 open-label clinical study using intravenous Paxceed(tm) to treat patients with rheumatoid arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): Angiotech Pharmaceuticals Purpose - Excerpt: Paxceed(tm) is being developed by Angiotech Pharmaceuticals, Inc. for the treatment of Rheumatoid Arthritis (RA). The main objective of this study is to determine the effectiveness of treatment with Paxceed(tm) in patients with RA. In RA, there is an increase in cell growth and changes in cell function. The active substance in Paxceed(tm), paclitaxel, has undergone clinical studies as a cancer chemotherapeutic agent and has demonstrated its usefulness as an agent that stops growth of cells and blocks certain types of cell function associated with RA. Because of these effects, it is thought that Paxceed(tm) might alter the destructive course of RA. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055133
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Clinically Important Changes in Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will explore how patients with rheumatoid arthritis evaluate, or rate, symptom improvements. Physicians generally evaluate patients' health and treatment benefits based on laboratory measures, such as the number of tender or swollen joints, duration of morning stiffness, grip strength, pain severity and others. Less attention is given to whether these treatment results are meaningful to patients. This study will examine how much of an improvement in pain, stiffness, function, and
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other symptoms is needed before patients consider the change an important improvement. Patients 18 years of age or older who were diagnosed with rheumatoid arthritis after age 16 and who have active arthritis (6 or more tender joints) may be eligible for this study. Of particular interest are patients beginning treatment with prednisone, methotrexate, leflunomide, infliximab, or etanercept, although patients receiving any type of treatment may be included. Participants will be evaluated twice at the NIH Clinical Center, once at the start of the study and again at either 1 month or 4 months later, depending on the individual's treatment regimen. Permission will also be requested to review patients' medical records for results of previous blood tests and xrays. At each NIH visit, patients will undergo the following tests and procedures: Medical history and physical examination, including evaluation of joint swelling and tenderness; - Questionnaires about rheumatoid arthritis symptoms; - Computer-based exercise to assess preferences for various state-of-health choices; - Grip strength test; Walking test on level ground, with or without the use of a cane or walker; - Blood test to measure inflammation. At the second visit, in addition to the above procedures, participants will complete a questionnaire to rate the importance of changes, if any, in pain, morning stiffness, fatigue, joint swelling, functioning, worry, depression, and overall impressions, since the first visit. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056602 •
Consistency of Traditional Chinese Medicine Diagnoses and Herbal Prescriptions for Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: Practitioners of Traditional Chinese Medicine (TCM) make diagnoses based solely on clinical symptoms. This study will evaluate whether TCM practitioners make diagnoses consistently. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071149
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Coping Skills Training for Early Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: Rheumatoid arthritis (RA) is the most common inflammatory arthritis and a major health problem. Medical treatments are now being used much earlier in the course of RA, but these treatments do not address the challenges of coping with the early stages of this disease. This study will determine whether a comprehensive coping skills training program can decrease pain, psychological disability, and physical disability in patients with early RA. Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056394 •
Effects of MEDI-522 On Disease Activity and Progression of Joint Damage in Patients with Active Rheumatoid Arthritis Suboptimally Responding to Methotrexate Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): MedImmune, Inc. Purpose - Excerpt: To compare, as a preliminary analysis, the effects of subcutaneously administered MEDI-522 versus placebo at 6 months on disease activity and progression of structural joint damage in patients with rheumatoid arthritis (RA), who have active disease despite ongoing treatment with methotrexate (MTX) with or without hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069017
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Efficacy & Safety of an Investigational Drug + Methotrexate Compared to Methotrexate Alone in Patients with Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: The purpose of this study is to help researchers confirm that an investigational drug given subcutaneously (injection given under the skin), once every 4 weeks, is an effective and safe treatment for rheumatoid arthritis in patients who are already taking methotrexate. Patients will be in this study for approximately 6 months and will need to attend the doctor's clinic on up to 12 occasions during that time. They will have a 50% chance of receiving the investigational drug and a 50% chance of receiving placebo in addition to their methotrexate. Prior to entry into this study patients will need to undergo chest x-ray and ECG (heart trace). Blood and urine tests, as well as arthritis assessments will be carried out regularly throughout the study, and patients will be required to complete health questionnaires at most clinic visits. Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048178
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Efficacy and Safety of Investigational Drug in Patients with Rheumatoid Arthritis Who Failed at Least One DMARD (Disease Modifying Anti-Rheumatic Drug) Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: A double-blind treatment with investigational drug compared to placebo in patients with rheumatoid arthritis Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00066105 •
ENBREL(R) (etanercept) as Treatment for Children with Systemic Onset Juvenile Rheumatoid Arthritis Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): Immunex Corporation Purpose - Excerpt: Rationale: etanercept inhibits the effects of tumor necrosis factor, which plays an important role in the progression of rheumatoid arthritis. A study of children with polyarticular course juvenile rheumatoid arthritis showed that Enbrel had efficacy and was generally well tolerated in children ages 4-17 who had moderately to severely active disease and who failed treatment with one or more disease modifying antiarthritic drugs. The children in the study may have had arthritis onset of pauciarticular, polyarticular, or systemic nature. Systemic onset juvenile rheumatoid arthritis (SOJRA) may result in approximately one-third of patients having significant long-term disability. Purpose: the Phase 4 study is designed to further define the safety and efficacy of etanercept in those children with SOJRA. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00039949
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ENBREL(R) (Etanercept) Safety Study in Children with Juvenile Rheumatoid Arthritis Condition(s): Arthritis, Juvenile Rheumatoid Study Status: This study is currently recruiting patients. Sponsor(s): Immunex Corporation Purpose - Excerpt: This Phase 4 open-label, nonrandomized multicenter registry study is being conducted to evaluate the long-term safety of ENBREL(R) (etanercept) compared to methotrexate in patients aged 2 to 18 years with polyarticular-course or systemiconset juvenile rheumatoid arthritis (JRA). Patients will be evaluated for a total of 3 years. The registry will include patients who have recently started and are currently receiving ENBREL alone, ENBREL in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs), methotrexate alone, or methotrexate in combination with other DMARDs. Approximately 600 patients will be enrolled at sites in the United States and Canada, with 400 patients receiving ENBREL and 200 receiving methotrexate without ENBREL. One group of patients will receive ENBREL by subcutaneous (SC) injection twice a week for up to 3 years and may continue taking other medicines such as prednisone or methotrexate. Another group will continue to receive methotrexate, either alone or in combination with DMARDs other than ENBREL. Candidates will be screened with a medical history and physical examination, including height, weight, and Tanner scores. A behavioral assessment, quality of life assessment, and physician's global assessment of disease activity will be performed. A blood test and joint evaluation will also be done. Both treatment groups will have on-study evaluations at baseline and months 3, 6, 9, 12, 18, 24, 30, and 36. Each follow-up visit will include a repeat of the screening assessments and an evaluation of adverse events or toxicity, including psychiatric and behavioral effects and new symptoms of autoimmune
338 Rheumatoid Arthritis
disorders. The two groups will be compared for safety, including effects on growth and development parameters. Patients will need to purchase or arrange the purchase of commercially available ENBREL. Patients entering the study during the period when ENBREL is in short supply will be able to obtain ENBREL after enrolling in the ENBREL Enrollment Program. Patients will receive ENBREL enrollment information at the time of registration into the study. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016575 •
Genetic Registry for Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute of Allergy and Infectious Diseases (NIAID); Arthritis Foundation Purpose - Excerpt: Many genes are thought to contribute to rheumatoid arthritis (RA). Currently only one such gene has been identified. This study will attempt to identify all of the genes that may contribute to RA and determine which specific genetic variations are responsible for the disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069472
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Identification of Genes Associated with Lung Disease in Patients with Rheumatoid Arthritis Condition(s): Healthy; Pulmonary Fibrosis; Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Pulmonary fibrosis (PF) is a condition in which the lungs of a patient become scarred and fibrous. It has been known to occur in as many as 40% of patients diagnosed with rheumatoid arthritis (RA). The cause of the pulmonary fibrosis in patients with RA is unknown. Data gathered from previous research studies suggest that genetics may play a role in the development of PF in patients with rheumatoid arthritis. However, the actual genetic factors involved in the disease process have not been identified. The goal of this study is to identify the genetic markers in patients with pulmonary fibrosis and rheumatoid arthritis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001885
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Infliximab for the Treatment of Early Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis
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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will test whether the drug combination of methotrexate and infliximab (anti-TNF-alpha antibody) is more effective than methotrexate alone for treating rheumatoid arthritis early in the disease. (The Food and Drug Administration has approved both treatment regimens for patients with long-standing rheumatoid arthritis.) The study will also evaluate how effectively magnetic resonance imaging (MRI) can detect differences in the development of bone damage in the two treatment groups by as early as 6 months. Patients 18 years of age and older who have had rheumatoid arthritis for less than 2 years and who have four or more affected joints may be eligible for this 1-year study. Patients must have received methotrexate treatment in the past without complete success, and must not have been treated previously with Anti-Thymocyte therapy. All participants will receive 20 Mg./week of methotrexate. In addition, patients will be randomly assigned to receive a monthly infusion of infliximab or placebo (a fluid that contains no active drug). After 6 months, all patients will receive active infliximab for the remaining half year of the study. Patients will also receive folic acid (1mg/day), Vitamin D (400 IU/day), and calcium supplements. They may continue to take prednisone (no more than 10 Mg./day) and non-steroidal anti-inflammatory drugs (NSAIDS). Medication dosages will be adjusted as needed if pain and joint swelling worsen. Over the course of the study, patients will come to NIH for 15 visits and undergo the following tests and procedures: 1. Joint examination-at every visit. 2. Drug side effects evaluation-at every visit during the study and after the study at 24 and 36 months by questionnaires to be filled out and returned. 3. Hand and feet X-rays at the first visit, at 6 months and at 12 months. 4. MRIs of the wrist to examine damage in the bone and synovial tissue (tissue lining the joint)-before treatment begins and at weeks 15, 27 and 54. For this study, the patient lies still in a narrow cylinder (the scanner) with a strong magnetic field. A contrast material (gadolinium) is injected into the blood to enhance the images of the synovium. The MRI takes about 45 minutes. 5. DEXA scans (dual emission X-ray absorptiometry) of the lower spine, one hip and one wrist to measure bone density and assess bone loss-before treatment begins and at weeks 27 and 54. This X-ray test takes about 5 to 10 minutes. 6. CTs (computed tomography) of one hand to assess joint damage in the wrist-before treatment begins and at weeks 27 and 54. Only half the patients in the study will have this X-ray study, which produces 3dimensional images of the hand. It will be done to compare the location, size and change of damage in the wrist seen on CT with the information obtained on MRI. The procedure takes about 5 to 10 minutes to complete. 7. Blood tests-at every visit to evaluate treatment response and side effects. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006292 •
Infliximab to Treat Children with Juvenile Rheumatoid Arthritis Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Purpose - Excerpt: This study will determine whether a stepwise increase of the drug infliximab (Remicade(r) (Registered Trademark)) controls juvenile rheumatoid arthritis more effectively than a fixed dose. It will look at the safety and effectiveness of increasing the dose to a maximum of 15mg/kg body weight per dose, examining the drug's effect on bone and cartilage, and whether it can improve abnormal growth, metabolism and hormones. Infliximab is approved for treating adults with rheumatoid arthritis and Crohn's disease. Children between 4 and 17 years of age with active juvenile rheumatoid arthritis who do not respond adequately to standard therapy may be eligible for this study. Participants will receive nine infusions of infliximab during this 62-week study. The drug is given intravenously (IV, into a vein) over 2 hours. The first three infusions will be at a dose of 5 mg/kg of body weight. Children who improve on this regimen will receive another 6 infusions at the same dose. Children who do not significantly improve on 5 mg/kg at the end of 6 weeks (the third infusion) may continue with phase 2 of the study, in which they will be randomly assigned to receive either: 1) 6 additional doses of the drug at 5 mg/kg per dose, or 2) a gradually increased dose to a maximum of 15 mg/kg. In addition, all children will continue to take methotrexate at the same dose as when they entered the study. Participants will visit the NIH Clinical Center 12 times (about every 8 weeks) during the study for the following tests and procedures: - History and physical examination, including a complete joint exam - Puberty assessment - breast development in girls, testicle size in boys, and pubic hair - Height and weight measurements Children will have imaging studies (x-rays, MRI and Dexa scan) at the beginning and end of the study and will collect a 24-hour urine sample before each infliximab infusion. Patients may elect to have an endocrine evaluation. This involves Clinical Center hospitalizations for 1-1/2 days on visits 1, 4 and 12. Small amounts of blood will be drawn every 20 minutes (through an indwelling catheter to avoid multiple needle sticks) for 8 hours while the child sleeps. The blood will be examined for the normal rhythm of growth hormone and other substances in the body and how they are affected by arthritis. Participants will complete a questionnaire once a year for 2 years to provide information on their health status and any problems that might be related to the study drug. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029042 •
ISIS 104838, an Inhibitor of Tumor Necrosis Factor, for Active Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): Isis Pharmaceuticals Purpose - Excerpt: ISIS 104838 is an antisense oligonucleotide drug that reduces the production of a specific protein called tumor necrosis factor (TNF-alpha), a substance that contributes to joint pain and swelling in rheumatoid arthritis. ISIS 104838 works by blocking TNF-alpha messenger RNA, the "instruction" molecule that is required for the production of TNF-alpha protein. This trial will assess the safety and efficacy of ISIS 1048383 by subcutaneous injection, administered by 3 different dosing regimens for 3 months, versus placebo. Approximately 160 TNF-alpha inhibitor-naïve rheumatoid arthritis patients will be evaluated at 32 sites in the U.S. and Canada. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048321 •
Long term safety and tolerability of an investigational drug in patients with rheumatoid arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: Open-label treatment with investigational drug in patients with rheumatoid arthritis to evaluate long term safety and tolerability and long term efficacy. Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055458
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Lung Disease Associated with Rheumatoid Arthritis Condition(s): Pulmonary Fibrosis; Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Pulmonary fibrosis (PF) is a condition in which the lungs of a patient become scarred and fibrous. It has been known to occur in as many as 40% of patients diagnosed with rheumatoid arthritis (RA). The cause of the pulmonary fibrosis in patients with RA is unknown. Patients participating in this study will undergo a series of tests and examinations before and throughout the study. The tests include blood and urine tests, electrical measures of heart function (ECG), chest x-rays, CAT scans, nuclear medicine scans, breathing tests, exercise tests, and fiberoptic bronchoscopy. The goals of this study are to: 1. Estimate how common pulmonary fibrosis is in patients with rheumatoid arthritis, 2. Describe the natural course of pulmonary fibrosis in patients with rheumatoid arthritis, 3. Estimate the survival rate of patients with pulmonary fibrosis and rheumatoid arthritis, and 4. Learn more about the factors that contribute to the development or progression fibrotic lung disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001876
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Phase I Study of High-Dose Cyclophosphamide, Anti-Thymocyte Globulin, and Total Body Irradiation With T-Cell-Depleted Autologous Bone Marrow Rescue in Patients With High-Risk Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis; Juvenile Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): Northwestern Memorial Hospital Purpose - Excerpt: Objectives: I. Determine the toxicity of high-dose cyclophosphamide, anti-thymocyte globulin, and total body irradiation with T-cell-depleted autologous bone marrow rescue in patients with high-risk rheumatoid arthritis. II. Determine the safety and efficacy of this regimen in this patient population.
342 Rheumatoid Arthritis
Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017615 •
Phase III Study of BMS-188667 (CTLA4Ig) in patients with rheumatoid arthritis who are currently failing anti-TNF therapy or who have failed anti-TNF therapy in the past. Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: The purpose of this clinical research study is to determine whether BMS-188667 will relieve the symptoms of rheumatoid arthritis in patients who are currently receiving anti-TNF therapy for at least 3 months and are not responding or have taken anti-TNF therapy in the last 3 months and did not respond. The safety of treatment with BMS-188667 will also be evaluated. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048581
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Relaxation Response Training for the Treatment of Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will evaluate the relative effectiveness of Relaxation Response (RR) training for the treatment of rheumatoid arthritis (RA). The study will compare RR training to RR training with cognitive behavioral therapy and to a standard RA education program. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056667
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Safety and efficacy of a monoclonal antibody for treatment of rheumatoid arthritis. Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): XOMA Purpose - Excerpt: The purpose of this study is to determine whether a humanized monoclonal antibody (efalizumab) is safe and effective in the treatment of rheumatoid arthritis.
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Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034203 •
Shared Epitope Peptides in Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will test whether a small protein, or peptide (dnaJ peptide) can help people with rheumatoid arthritis (RA) by preventing their immune system cells from abnormally reacting against the body's own tissues. This study will look at whether taking small amounts of dnaJ peptide by mouth can "re-educate" immune cells in some people with RA so that the cells become tolerant to, or get used to, this substance and stop attacking joint tissues. The study involves a screening, treatment, and follow-up phase. If the person qualifies for the study, he or she will be assigned to one of two groups. One group will receive the placebo (an inactive substance) and the other group will receive the study drug (dnaJ peptide). We will examine study participants, collect their blood and urine for testing, and ask them to answer a questionnaire about their arthritis once every 4 weeks over a period of 24 weeks of treatment and at a follow-up visit one month after the end of the treatment period. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000435
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Specimen Collection for Individuals with Lung Disease Associated with Rheumatoid Arthritis Condition(s): Pulmonary Fibrosis; Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Pulmonary fibrosis (PF) is a condition in which the lungs of a patient become scarred and fibrous. It has been known to occur in as many as 40% of patients diagnosed with rheumatoid arthritis (RA). The cause of the pulmonary fibrosis in patients with RA is unknown. Researchers hope to improve their understanding of the disease process involved in PF and RA by analyzing specimens collected by bronchoscopy, lung biopsy, lung transplantation, or autopsy from patients with these conditions. The purpose of this study is to collect specimens from rheumatoid arthritis patients with and without pulmonary fibrosis as well as patients with pulmonary fibrosis without associated diseases or cause (idiopathic pulmonary fibrosis). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001884
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Study of Families with Twins or Siblings Discordant for Rheumatic Disorders Condition(s): Rheumatic Diseases; Rheumatoid Arthritis; Erythematosus; Scleroderma; Dermatomyositis; Myositis
Systemic
Lupus
Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: This study will examine families in which one sibling of a sibling pair, or twin pair, has developed a systemic rheumatic disease and one has not, to see if and how the two differ in the following: - Blood cell metabolism; - Types of cells in the blood; - Environmental exposures or genetic factors that might explain why one developed disease and the other did not. Families in which one sibling has developed a systemic rheumatic disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, dermatomyositis, or myositis, and the other has not, are eligible for this study. The siblings may or may not be twins, but must be of the same gender and be within a 3-year age difference. Biological parents, or, in some cases, children, will also be included in the study. Normal, healthy volunteers will serve as control subjects. Participants will undergo some or all of the following tests and procedures: - Medical history and physical examination. Participants will also be asked permission to obtain medical records for review. - Questionnaires about environmental exposures at work, at home, and elsewhere. Probands (participants with rheumatic disease) and their healthy siblings will also answer questions about infections, vaccinations, medications or dietary supplements, sun exposure, and stressful events during the year before disease diagnosis in the affected sibling. - Blood and urine collection for the following tests: Routine blood chemistries and other studies to rule out certain diseases or medical problems; - Evidence of past toxic exposures and certain infections; - Presence of cells from the mother in the child's blood and vice versa. (Recent studies suggest that during pregnancy or delivery, cells from the mother and baby may be exchanged and circulate in the body for many years, possibly causing problems); - In twin or sibling pairs, presence of certain genes that may be more common in patients with systematic rheumatic diseases as compared with their unaffected siblings and normal volunteers; In identical twins, comparison of their blood cell metabolism to see if and how the metabolism differs in people with rheumatic disease. Participants may be asked for permission to have some of their blood and urine samples stored and to obtain previously collected blood or tissue biopsy specimens that are no longer needed for clinical care, for research purposes. They may also be asked to give additional blood or urine samples. Participants will be followed every year for 5 years (either in person or by questionnaire) to evaluate any changes in their condition. The final 5-year evaluation will repeat some of the questionnaires and procedures described above. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055055 •
The Role of Cytokines on Growth Hormone Suppression in Premenopausal Women with Rheumatoid Arthritis and the Effect of Treatment with Etanercept Condition(s): Rheumatoid Arthritis; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Purpose - Excerpt: This study has two phases. Phase 1 will examine the role of inflammatory mediators called cytokines on growth hormone levels in women with rheumatoid arthritis (RA). Phase 2 will evaluate the effect of etanercept on these growth hormone levels. Etanercept is approved for the treatment of RA. It lowers the levels of a key inflammatory mediator called tumor necrosis factor-alpha and is very effective in reducing arthritis symptoms. Growth hormone promotes bone and muscle growth. With aging, people lose muscle mass and bone strength, possibly because of decreased levels of growth hormone. People with RA have bone and muscle changes similar to those in older people, perhaps also due to decreased levels of growth hormone. The first part of this study will see if the inflammatory mediators responsible for joint inflammation (warmth, redness, pain, and swelling) in RA are related to the lowered growth hormone levels in this disease. The second part will evaluate the effect of etanercept treatment on muscle mass and bone density, in addition to growth hormone levels. Premenopausal women between 18 and 55 years of age with a recent diagnosis of rheumatoid arthritis (less than 3 years) are eligible for this study. Healthy volunteers will also be enrolled in the first phase of the study as control subjects. This study is conducted at two sites, the NIH and the Johns Hopkins Medical Center in Baltimore. Healthy volunteers enrolled in this study will be interviewed about their health status and will fill out questionnaires on diet and general physical function, including fatigue, energy and well being. In addition, they will be hospitalized once at the NIH Clinical Center for 24-hour blood sampling and will visit to Johns Hopkins Medical Center in Baltimore for a brachial artery reactivity study, as follows: - 24-hour blood sampling for growth hormone levels. Blood samples (1/2 teaspoon each) will be collected every 20 minutes from 8 AM one day until 8 AM the following day through a plastic tube in an arm vein. - Dual energy X-ray absorptiometry (DEXA) scan on a small area of the spine, hip and wrist to assess bone density and a total body DEXA scan to assess the amount and distribution of muscle and body fat. - Blood vessel (brachial artery reactivity) study to measure the ability of the brachial artery to dilate and increase its blood flow. For this procedure, the subject lies on a table with electrocardiogram leads attached to the chest. A blood pressure cuff is inflated for several minutes and a drop of nasal spray of nitroglycerin is given that may cause a headache. Blood pressure and headache are monitored and treated as needed. Patients with rheumatoid arthritis will be seen at the NIH clinic on six separate visits (weeks 0, 1, 6, 12, 18, and 26) over 26 weeks. Week 0 is a screening visit. At weeks 1 and 26, patients will be admitted to the hospital for 24-hour blood sampling, DEXA scans, and brachial artery reactivity tests, as described above, plus X-rays of the hand and feet. After the first visit, they will start taking etanercept, given by self-injection under the skin (like insulin shots) twice a week. Follow-up visits at weeks 6, 12, and 18 will involve evaluations of disease activity and drug side effects through joint examination, blood tests, and questionnaires. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034060 •
Treating Rheumatoid Arthritis with Tripterygium Wilfordi Hook F or Sulfasalazine Condition(s): Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Purpose - Excerpt: Various forms of the plant extract Tripterygium wilfordi Hook F (TwHF) have been used in China as a remedy for inflammatory diseases, including rheumatoid arthritis. The purpose of this study is to investigate how tolerable, safe, and effective TwHF is for patients with rheumatoid arthritis. Investigators will compare the therapeutic effects of TwHF with Sulfasalazine, an FDA-approved drug for arthritis. Participants in this 24-week study must have had active rheumatoid arthritis for at least six months. Approximately 120 patients will participate. Participants will be assigned to one of two drug-treatment groups, TwHF or Sulfasalazine. They will be given the study drug at each of six clinic visits and will be asked to take two capsules three times each day with meals and water. During the clinic visits, investigators will obtain multiple blood samples; give physical exams; assess swollen, tender, and painful joints; and administer x-rays. Study participants will be compensated up to $260 for their involvement in this study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062465 •
A Phase III Study of BMS-188667 in patients with active rheumatoid arthritis and inadequate response to methotrexate Condition(s): Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): Bristol-Myers Squibb Purpose - Excerpt: The purpose of this clinical research study is to learn if BMS-188667 in combination with methotrexate is better than methotrexate alone in subjects that have active rheumatoid arthritis and are not responding to methotrexate. The safety of this treatment will also be studied. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048568
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Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases Condition(s): Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis Study Status: This study is no longer recruiting patients. Sponsor(s): Fairview University Medical Center Purpose - Excerpt: Objectives: I. Determine whether there is prompt engraftment after autologous peripheral blood stem cell transplantation using filgrastim (G-CSF) mobilization in patients with life threatening autoimmune diseases. II. Determine the kinetics of T- and B-cell immune reconstitution after a combination of timed
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plasmapheresis, high dose cyclophosphamide and total lymphoid irradiation, and posttransplant immunosuppression with cyclosporine in these patients. III. Determine whether this treatment regimen beneficially influences the clinical course of these patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006055 •
Calcium Supplements for Bone Health in Juvenile Rheumatoid Arthritis Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study looks at the effects of taking calcium pills on bone health in young people with juvenile rheumatoid arthritis (JRA). In this 2-year study, children aged 6-18 who have JRA will take either a calcium supplement or a matching placebo (inactive or "dummy" pill) containing no calcium. During the study, researchers and patients will not know if a patient is taking calcium or placebo. We believe that patients who take calcium supplements will have at least a 10 percent greater increase in total body bone mineral density compared to patients who take the placebo. We will evaluate patients at Children's Hospital Medical Center every 6 months for 2 years. During this 2year period, participants in the study will take one multivitamin containing 400 IU (international units) of vitamin D and either 1,000 mg of calcium carbonate (Tums tablets) by mouth or a matching placebo once a day. We will check patients 6 and 18 months after the 2-year treatment period to find out if people in the Tums-treated group maintain any increases in bone formation that occurred during the 2-year treatment period. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000429
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Evaluation of the Efficacy of Combination Treatment with Anakinra and Pegsunercept in Improving Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): Amgen Purpose - Excerpt: The purpose of this study is to evaluate the effect of anakinra (IL-1 ra) and pegsunercept (PEG sTNF-RI) when they are used together in improving the signs and symptoms of rheumatoid arthritis. The study will also evaluate the safety of the combination treatment and its effect on slowing down bone and joint destruction due to rheumatoid arthritis. The results will be compared to the effect when only 1 single medication (anakinra or pegsunercept) is used. Phase(s): Phase II Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037700 •
Genetics of Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study attempts to identify the genes responsible for rheumatoid arthritis (RA), or inflammation of the joints. It is known that genes play an important role in RA, but their number and significance have not been determined. RA tends to run in families. This study will examine the DNA (hereditary material) of patients with RA and their family members to try to determine which chromosomes(s) contain the genes responsible for the disease. Patients with rheumatoid arthritis and their family members may be eligible for this study. Participants with RA who have a brother or sister with RA will undergo the following procedures: -Review of their medical records Medical history -Examination of the joints -Hand X-rays -Blood tests Participants who 1) do not have RA but who have a relative with the disease, or 2) have RA and a relative other than a brother or sister who has the disease will provide a blood sample or a buccal (cheek) cell sample. Cheek cells are obtained by swishing a small amount of mouthwash in the mouth or by lightly bushing the inside of the cheek with a swab or brush. The samples will be tested for rheumatoid factor, DNA studies, and HLA type (a blood type found on white blood cells). Certain HLA types have been associated with an increased risk or severity of RA. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001678
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Juvenile Rheumatoid Arthritis Condition(s): Juvenile Chronic Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): Amgen Purpose - Excerpt: The purpose of this study is to determine the safety and effectiveness of anakinra in patients with Polyarticular-Course Juvenile Rheumatoid Arthritis, a form of rheumatoid arthritis affecting children. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037648
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Meloxicam suspension in Juvenile Rheumatoid Arthritis (JRA) Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): Boehringer Ingelheim Pharmaceuticals
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Purpose - Excerpt: The purpose of this 6 month study is to determine how safe and effective meloxicam oral suspension (liquid taken by mouth) is in children with JRA. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034853 •
Oral Collagen for Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This protocol allows us to determine whether doses of CII from 30130ug/day will induce oral tolerance to CII in RA patients. This will be a 2 year MultiCenter Clinical Trial (CT) with the University of Tennessee, Memphis as the Lead Center to determine whether oral administration of 6 different doses of bovine type II collagen (CII) to patients with rheumatoid arthritis (RA) will induce immune tolerance defined as a >30% reduction in IFN gamma/PBMC alpha 1(II)/PBS stimulation index. Patients will be enrolled with stable RA, without stopping DMARDs, NSAIDs or prednisone (equal to or less than 7 1/2 mg daily) and the study will not be restricted to patients with early disease. Patients taking NSAIDS will take misoprostol 100ug bid. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000401
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Safety Study for Remicade Condition(s): Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): Centocor Purpose - Excerpt: To assess the relative risk for serious infection in infliximab-treated patients within the first 22 weeks after initiation of therapy in a population of patients with rheumatoid arthritis (RA) reflective of the demographics (severity of RA, background disease-modifying anti-rheumatic drugs, concomitant diseases) seen in clinical practice. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036387
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Study to Assess Efficacy of Tacrolimus + Methotrexate Vs. Placebo + Methotrexate in Treatment of Rheumatoid Arthritis Condition(s): Rheumatoid Arthritis
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Study Status: This study is no longer recruiting patients. Sponsor(s): Fujisawa Healthcare, Inc. Purpose - Excerpt: The purpose of this study is to evaluate the efficacy of the combination of tacrolimus + methotrexate compared to methotrexate alone in the treatment of the signs and symptoms of rheumatoid arthritis over 6 months in patients with partial response to methotrexate. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036153 •
Trial with HuMax-CD4 in Patients with Rheumatoid Arthritis failing treatment with Methotrexate and a TNF-alpha blocker. Condition(s): Rheumatoid Arthritis Study Status: This study is no longer recruiting patients. Sponsor(s): Genmab Purpose - Excerpt: The purpose of this study is to determine whether HuMax-CD4 is effective in the treatment of active rheumatoid arthritis in patients who have failed treatment with Methotrexate and at least one TNF-alpha blocking agent. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042406
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A multi-center trial to compare the efficacy and safety of three doses of Meloxicam and placebo in patients with Rheumatoid Arthritis. Condition(s): Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): Boehringer Ingelheim Pharmaceuticals Purpose - Excerpt: A 12-week trial consisting of 5 visits (6 if follow up is needed) to find out how effective and safe three different doses of meloxicam are compared with placebo in Rheumatoid Arthritis. Patient will take one dose of study medication daily. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042068
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A Phase III study of BMS-188667 in subjects with active rheumatoid arthritis Condition(s): Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): Bristol-Myers Squibb
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Purpose - Excerpt: The purpose of this clinical research study is to learn if BMS-188667 is safe when co-administered with other approved rheumatoid arthritis medications. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048932 •
Antifolate Effectiveness in Arthritis Condition(s): Rheumatoid Arthritis; Adjuvant Arthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Dietary Supplements (ODS) Purpose - Excerpt: This study looks at how the arthritis drug methotrexate works in low doses to treat rheumatoid arthritis. (High doses of methotrexate are used to treat some types of cancer.) Methotrexate blocks the action of the B-vitamin known as folic acid. We are studying the biochemical reactions affected by this vitamin because we think that blocking many of these reactions may be necessary for methotrexate to work in treating rheumatoid arthritis. Through these studies, we hope to gain a better understanding of how this drug and related drugs work as treatments for arthritis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000395
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Genetic and Immune Studies of Rheumatoid Arthritis and Related Conditions Condition(s): Arthritis, Psoriatic; Autoimmune Diseases; Joint Diseases; Osteoarthritis; Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This protocol will examine blood, synovial fluid and synovial tissue from patients with rheumatoid arthritis and other chronic inflammatory joint diseases to study genetic and immunologic factors involved in the cause, development and progression of these conditions. Synovial fluid is the lubricating fluid in joints. The synovial membrane is a delicate tissue lining the inner surface of joints, which, in arthritic conditions, thickens and becomes infiltrated with various types of cells. Patients with rheumatoid arthritis and certain patients with other forms of arthritis may be eligible for this study. Those enrolled will be followed periodically for follow-up and disease evaluation. They may undergo the following procedures: 1. Synovial fluid aspiration, when medically indicated (for example, for joint swelling and inflammation). For this procedure, an area of skin around the joint is numbed with an anesthetic, and a needle is inserted into the joint to withdraw a small fluid sample. 2. Periodic blood sampling, not to exceed 450 milliliters (15 ounces) during any 6-week period, for genetic studies of rheumatoid arthritis. The samples are usually taken at the same times that synovial fluid is withdrawn. 3. Synovial tissues, collected by needle biopsy or during
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surgical procedures for arthroscopy (examination of the interior of the joint and repair of the joint) or total joint replacement. For the needle biopsy, the skin over the biopsy site is washed and anesthetized. A needle is inserted and fluid is aspirated. The biopsy needle is then inserted through the outer needle and a tissue sample is suctioned. Patients who qualify for other research studies may be invited to participate. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001291 •
Methotrexate Alone Versus Combination of Methotrexate and Subcutaneous Fludarabine for Severe Rheumatoid Arthritis: Safety, Tolerance and Efficacy Condition(s): Arthritis, Rheumatoid; Synovitis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The safety profile and efficacy of combination therapy will be evaluated using methotrexate (MTX) and the nucleoside analog fludarabine in 40 patients with severe refractory rheumatoid arthritis. The patients enrolled will be those who have experienced inadequate disease control with MTX alone or in combination with other immunosuppressive drugs such as sulfasalazine (SSZ), cyclosporin A (CsA), or hydroxychloroquine (HCQ). In this randomized, double-blind, placebo controlled trial, patients will be maintained on oral MTX at 17.5 mg/week to which either placebo or subcutaneous fludarabine at 30 mg/m(2) daily for three consecutive days per month will be added for four months. The fludarabine (or placebo) treatment period will be followed by two months of follow-up, at which time patients will be evaluated for response. Patients will be monitored for adverse effects/tolerability, disease activity, and changes in synovial volume as measured by magnetic resonance imaging (MRI). Additionally synovial biopsies will be obtained before and after treatment for investigation of infiltrating cell numbers and phenotypes, cytokine profiles, Th1 versus Th2 responses, and angiogenesis. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001677
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Patient Education in Rheumatoid Arthritis and Osteoarthritis Condition(s): Rheumatoid Arthritis; Osteoarthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This project will evaluate the effectiveness and general usefulness of two arthritis patient education programs. The first, the Arthritis Self-Management Program, is a 6-week, community-based program taught in small groups by peer leaders. The second, the Self-Managed Arthritis Relief Therapy (SMART) Program, is a computer-driven program delivered through the mail. Participants in this project are people with rheumatoid arthritis or osteoarthritis who are taking part in the larger long-
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term studies being conducted by ARAMIS (the Arthritis, Rheumatism and Aging Medical Information System). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000414 •
Positron Emission Tomography and Magnetic Resonance Imaging to Evaluate Synovial Blood Flow in Rheumatoid Arthritis Patients Condition(s): Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will test whether positron emission tomography (PET) imaging can be used to measure blood flow to joints in patients with rheumatoid arthritis (RA). It will also compare blood flow measurements using PET with measurements obtained with magnetic resonance imaging (MRI) to determine how useful MRI is in measuring blood flow to joints. Much of the joint damage in RA is caused by the synovium-the lining of the joint. In RA, the synovium increases in size and destroys bone and cartilage. The synovium maintains its growth by forming many new small blood vessels to nourish it. New drug treatments are being developed to stop the growth of these new blood vessels. The effect of these treatments on the synovium is usually measured by performing a biopsy-removing a small piece of synovium for examination under a microscope. The biopsy requires inserting a needle into the joint to withdraw the synovial tissue. This study will see if changes in blood flow can be assessed accurately using noninvasive imaging procedures, such as PET scanning, instead of a biopsy. Patients 18 years of age and older with rheumatoid arthritis who have at least one tender and swollen knee due to synovitis may be eligible for this study. Candidates will be screened with a medical history and physical examination. Participants will have a mold made of the knee to be studied and will have routine blood tests. Women who are able to become pregnant will have a pregnancy test. All participants will then undergo PET and MRI scanning as described below: PET - A needle is used to insert a catheter (small plastic tube) into an arm vein for injection of the radioactive substance H215O. The patient lies in a doughnut-shaped machine (the PET scanner) and a quick scan is done to measure body thickness. Then, a separate scan is taken following each of six or fewer injections of H215O. Each scan lasts about 13 minutes. MRI - The patient lies on a stretcher that is moved into a cylinder containing a magnetic field (the MRI scanner). A special coil is placed over the knee to improve the quality of the images. Earplugs are worn to muffle the loud thumping sound produced by electrical switching of the magnetic fields during the imaging. A contrast agent called gadolinium is injected through a catheter into a vein to improve the quality of the images. An intercom system permits the patient to communicate with the technician at all times during the procedure. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00014794
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Study of Gammalinolenic Acid for Juvenile Rheumatoid Arthritis Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development; University of Massachusetts Medical Center Purpose - Excerpt: Objectives: I. Determine the efficacy and safety of gammalinolenic acid in the treatment of childhood arthritis. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004420
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Study of infliximab in combination with methotrexate for the treatment of patients with polyarticular juvenile rheumatoid arthritis Condition(s): Juvenile Rheumatoid Arthritis Study Status: This study is completed. Sponsor(s): Centocor Purpose - Excerpt: Research study to evaluate the safety and effectiveness of an investigational drug is currently being conducted in children diagnosed with polyarticular juvenile rheumatoid arthritis with active disease while receiving methotrexate therapy. Aim of the international study is to evaluate the efficacy and safety of the drug in patients with active JRA/JIA who are receiving methotrexate therapy. Study is being conducted in Belgium, Canada, Finland, France, Germany, Italy, the Netherlands, Spain, Sweden, Switzerland, United Kingdom, and USA. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036374
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The Safety and Efficacy of Chicken Type II Collagen on Uveitis Associated with Juvenile Rheumatoid Arthritis Condition(s): Arthritis, Juvenile Rheumatoid; Uveitis Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: Current treatment modalities for uveitis associated with juvenile rheumatoid arthritis have not been beneficial in the juvenile population. A new approach for treating patients with presumed autoimmune disorders is oral tolerance therapy. Chicken type II collagen (Colloral) is being developed as an oral tolerance therapy for the treatment of rheumatoid arthritis. This open label pilot study will describe the safety of chicken type II collagen added to current anti-inflammatory medications as treatment for patients with uveitis associated with juvenile rheumatoid arthritis. The primary ophthalmic outcomes of this study will be a change from baseline in the number of anterior chamber cells and the number and dosage of antiinflammatory medications. Secondary outcomes for JRA will include change in physician's global assessment, parent/patient assessment of overall well-being,
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functional assessment, number of joints with active arthritis, number of joints with limited range of motion, and erythrocyte sedimentation rate (ESR). Secondary outcomes for uveitis will include change in visual acuity, vitreous haze, and anterior chamber flare. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001614 •
TNRF:Fc to Treat Eye Inflammation in Juvenile Rheumatoid Arthritis Condition(s): Juvenile Rheumatoid Arthritis; Uveitis Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will investigate the safety and effectiveness of the drug TNFR:Fc to treat uveitis (eye inflammation) in patients with juvenile rheumatoid arthritis. In other studies, TNFR:Fc significantly reduced joint pain and swelling in adult patients with rheumatoid arthritis, and the Food and Drug Administration has approved the drug for that use. Because medicines for arthritis often help patients with eye inflammation, this study will examine whether TNFR:Fc can help patients with uveitis. Patients with uveitis who are not responding well to standard treatment, such as steroids, and patients who have side effects from other medicines used to treat their uveitis or have refused treatment because of possible side effects may be eligible for this study. Candidates will be screened with a medical history, physical examination, and eye examination. The eye exam includes a check of vision and eye pressure, examination of the back of the eye (retina), and front of the eye, including measurements of protein and inflammation. Candidates will also undergo fluorescein angiography-a procedure in which photographs are taken of the retina to see if there is any leakage in the eye's blood vessels. A blood test and joint evaluation will also be done. Study participants will be given a shot of TNFR:Fc twice a week for up to 12 months and may continue other medicines they may be taking, such as prednisone or methotrexate. They will have follow-up examinations at week two and months one, two, three and four. Those who wish to continue treatment after the fourth month can receive the drug for another eight months and will have follow-up exams at months six, nine and 12, and one month after treatment ends. Each follow-up visit will include a repeat of the screening exams and an evaluation of side effects or discomfort from the medicine. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001862
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions.
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The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “rheumatoid arthritis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON RHEUMATOID ARTHRITIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “rheumatoid arthritis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on rheumatoid arthritis, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Rheumatoid Arthritis By performing a patent search focusing on rheumatoid arthritis, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on rheumatoid arthritis: •
1-[4-(4-Sulfanilyl)phenyl] urea and derivatives in compositions and methods of treating rheumatoid arthritis and immune complex diseases Inventor(s): Jones; Howard (Holmdel, NJ), Jacobus; David P. (Princeton, NJ), Jensen; Norman P. (New Providence, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 4,338,334 Date filed: February 29, 1980 Abstract: The invention relates to 1-[4-(4-sulfanilyl)phenyl] urea and derivatives thereof in pharmaceutical compositions and in methods of treating rheumatoid arthritis and immune complex diseases such as dermatitis herpetiformis. Excerpt(s): The present invention is concerned with pharmaceutical compositions containing as an active ingredient the known compound 1-[4-(4-sulfanilyl)phenyl]urea and known derivatives thereof, and the use of these compositions, or the compounds themselves, in treating rheumatoid arthritis, muscular dystrophy, immune complex diseases, including dermatitis herpetiformis, celiac disease, and certain forms of leukemia, and autoimmune endocrine diseases such as juvenile diabetes. Dapsone (4,4'diaminodiphenylsulfone) is an established antimalarial and antileprotic agent. It has been found to be effective in treating rheumatoid arthritis; see McConkey et al., Rheumatology and Rehabilitation, 1976, 15, 230-234. It has also been employed in clinical treatment of dermatitis herpetiformis; see Lorincz and Pearson, "Sulfapyridine and Sulfone Type Drugs in Dermatology", Arch. Derm. 85: 42-56 (1962). Derivatives of diaminodiphenyl sulfone have been described in the literature for many years; see E. H. Northey, "Sulfonamides", A.C.S. monograph No. 106 (1948). The compound 1-[4-(4sulfanilyl)phenyl]urea, as well as a variety of substituted diphenyl sulfones have been found useful in reducing mortality and decreasing lesion incidence of poultry exposed to Marek's disease. See U.S. Pat. Nos. 3,689,671; 3,702,362; 3,715,375; 3,775,403; 3,775,444; and 3,786,050. However, none of these patents suggests the use of the substituted diphenyl sulfones disclosed therein as agents for treating rheumatoid arthritis, muscular dystrophy, or immune complex diseases. The compound 1-[4-(4-sulfanilyl)phenyl]urea, and several substituted diphenyl sulfones have been found to inhibit the incorporation of chloline in chick peritoneal macrophages, an activity associated with the ability of such compounds to suppress growth or function of Marek's disease virus. See Shigeura et al., "Metabolic Studies on Diphenylsulfone Derivatives in Chick Macrophages", Biochemical Pharmacology, Vol. 24, pp. 687-691 (1975). Web site: http://www.delphion.com/details?pn=US04338334__
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Acyl cyanoguanidines for treating rheumatoid arthritis Inventor(s): Shen; Tsung-Ying (Westfield, NJ), Jones; Howard (Holmdel, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 4,202,903 Date filed: September 30, 1975
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Abstract: Certain novel acyl cyanoguanidines, their preparation, pharmaceutical compositions and novel methods of treating inflammation and autoimmune diseases such as rheumatoid arthritis are disclosed. Excerpt(s): In spite of the extensive antiinflammatory research in the past two decades there is still an obvious need for an effective and well-tolerated agent for the treatment of rheumatoid arthritis. Conventional antiinflammatory-analgesic-antipyretic agents, such as aspirin, and many experimental new drugs under clinical evaluation, are mostly effective in providing symptomatic relief of the acute syndrome only. As a consequence, the antirheumatic actions of two other remedies, gold and particularly D-penicillamine, have received renewed interest in the past few years. The clinical efficiancy of both drugs has been confirmed by well-controlled multi-center clinical studies. Impressed by these findings, a growing population of rheumatologists have expressed the opinion that compounds possessing properties similar to D-penicillamine should be a valuable contribution to medicine in this important field. Thus it is an important discovery that acyl cyanoguanidines possess immunological properties similar to that of Dpenicillamine, being of value in the treatment of rheumatoid arthritis and related inflammatory disorders, as well as antiinflammatory properties. 1-[3'-(4'methylthionicotinoyl)]-3-cyanoguanidine. Another aspect of this invention relates to the novel pharmaceutical compositions for treating inflammation and autoimmune diseases, such as rheumatoid arthritis, comprising a non-toxic pharmaceutically acceptable carrier and a compound of the formula I, supra, wherein R is as defined above. Web site: http://www.delphion.com/details?pn=US04202903__ •
Anti immune complex antibody for determining SLE, rheumatoid arthritis or tetanus Inventor(s): Kasahara; Yasushi (Tokyo, JP), Soma; Kazunori (Tokyo, JP) Assignee(s): Fujizoki Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 4,544,640 Date filed: April 7, 1983 Abstract: An antibody is obtained by using as an antigen a complex of an antigen and the F(ab').sub.2 fragment of the human antibody of this antigen or an aggregate of the F(ab').sub.2 fragment of human immunoglobulin. This antibody reacts with an immune complex in a blood serum of a patient of systemic lupus erythematosus and with an immune complex in a blood serum of a patient of rheumatoid arthritis, and it does not react with an aggregated IgG. The amount of immune complex in a blood serum is easily and exactly determined by using this antibody. Excerpt(s): This invention related to a novel antibody capable of detecting an immune complex and relates to its preparation method and use. Immune complex is the combined product of an antigen, an antibody and a complement. When this immune complex is formed in a human body, the immune complex is usually rendered harmless by a leucocyte or a macrophage. However, when a large quantity of antigen exists in a human body, or when an antigen the antibody of which forms with difficulty, exists in a human body, the amount of immune complex increases, and it causes various diseases such as acute glomerulonephritis, angitis, chronic urticaria, and thrombocytopenia. Various measuring methods of this immune complex are known such as the method utilizing a reaction of complement or rheumatoid factor with the immune complex, the method utilizing a reaction of the Fc receptor with the immune complex, and various
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physicochemical methods such as the gel filtration method, the sucrose density gradient centrifuge and precipitation with polyethyleneglycol. However, the method using the complement or rheumatoid factor and the method using Fc receptor have a fatal defect in that these methods cannot distinguish between aggregated IgG and the immune complex. The physicochemical methods are complicated and they are insufficient in specificity. Web site: http://www.delphion.com/details?pn=US04544640__ •
Antibody against rheumatoid arthritis specific protein Inventor(s): Yamanaka; Naoki (Nagoya, JP), Yoshida; Makoto (Kawasaki, JP) Assignee(s): Asahi Medical Co., Ltd. (Tokyo, JP), Medecs Co., Ltd. (Nagoya, JP) Patent Number: 4,950,741 Date filed: February 16, 1988 Abstract: A substantially pure rheumatoid arthritis specific protein (RASP) and an antibody against the rheumatoid arthritis specific protein (anti-RASP antibody) are disclosed. The RASP is found specifically in the serum or plasma of a patient suffering from rheumatoid arthritis, and may be detected using an anti-RASP antibody easily and effectively. Therefore, the anti-RASP antibody of the present invention is useful for the diagnosis of rheumatoid arthritis by the criterion of the presence of RASP. Excerpt(s): (3) an electrophoretic mobility of about 0.30 to 0.45 in terms of a value as measured by a two-dimensional electrophoresis method as defined herein. and which antibody has a molecular weight of about 150,000 to 160,000 in terms of a value as measured by an SDS-polyacrylamide gel electrophoresis method as defined herein. Now, a substantially pure rheumatoid arthritis specific protein of the present invention will be explained below. Web site: http://www.delphion.com/details?pn=US04950741__
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Antigens recognized by antibodies to rheumatoid arthritis, their preparation and their applications Inventor(s): Serre; Guy (Toulouse, FR), Vincent; Christian (Lauzerville, FR), Somme; Gerard (Bures Sur Yvette, FR) Assignee(s): Biomerieux S.A. (Marcy L'Etoile, FR) Patent Number: 5,888,833 Date filed: June 3, 1994 Abstract: The present invention relates to antigens extracted from mammalian malpighian epithelia, in particular rat esophageal epithelium or human epidermis, which are specifically recognized by the autoantibodies present in patients suffering form rheumatoid arthritis in respect of antigenic determinants in common with filaggrin and human profilaggrin, as well as to the antigenic proteins of which said antigens are composed and to the peptide fragments derived therefrom. The invention relates to the use of these antigens, proteins and peptide fragments, and that of filaggrin and human profilaggrin, for the preparation of antigenic compositions, and to their applications, in particular for the diagnosis of rheumatoid arthritis. The invention also relates to the preparation of antibodies directed towards these antigens, and to their applications.
Patents 361
Excerpt(s): The present invention relates to the use of human filaggrin and antigens related thereto for the diagnosis or treatment of rheumatoid arthritis (RA). The presence of autoantibodies directed towards cellular components is the general feature of autoimmune diseases such as RA, systemic lupus erythematosus, scleroderma or polymyositis. Among the many types of autoantibodies identified in these diseases, those specifically present in patients suffering from RA and reacting with an esophageal epithelial antigen were described for the first time by B. J. J. Young et al. in Br. Med. J. 2:97-99, (1979). These autoantibodies were named at the time "antikeratin antibodies". Hitherto, it was commonly accepted that they were directed towards cytokeratins. These autoantibodies specific to RA are at the present time detected and titrated by indirect immuno-fluorescence (IIF) on transverse cryosections of rat esophagus. Web site: http://www.delphion.com/details?pn=US05888833__ •
Anti-human stromelysin monoclonal antibody and method for diagnosis of rheumatoid arthritis by enzyme immunoassay Inventor(s): Hayakawa; Taro (406, Mukaigaoka 3-chome, Tenpaku-ku, Nagoya-shi, Aichi-ken, 468, JP), Kodama; Shuji (603, Takaokasukaihaitsu, 1868, Nagae, Takaoka-shi, Toyama-ken, 933, JP), Shinmei; Masayoshi (4-4, Nakaaral 4-chome, Tokorozawa-shi, Saitama-ken, 359, JP), Okada; Yasunori (32, Wakamiya 2-chome, Matto-shi, Ishikawaken, 924, JP), Iwata; Kazushi (190 Ikarihigashimachi, Takaoka-shi, Toyama-ken, 933, JP), Korin; Yumi (Fu-134, Takamatsucho, Kahoku-gun, Ishikawa-ken, 929-12, JP), Yoshida; Shinichi (13-16, Nakajima 4-chome, Toyama-shi, Toyama-ken, 930, JP) Assignee(s): none reported Patent Number: 5,834,212 Date filed: April 6, 1995 Abstract: Anti-human stromelysin monoclonal antibodies reactive with latent and active forms of stromelysin without discrimination between the two, each being immunoreactive with only one of the antigenic determinants of human stromelysin, are provided. The use of a combination of two such monoclonal antibodies which specifically react with different antigenic determinants of human stromelysin renders it possible to accurately determine the amount of human stromelysin in human body fluids, and thus to carry out the diagnosis of rheumatoid arthritis.There are thus provided said monoclonal antibodies per se, a sandwich enzyme immunoassay for the determination of the amount of human stromelysin in human body fluid samples using a combination of two such monoclonal antibodies, and a method for the diagnosis of rheumatoid arthritis using said immunoassay. Excerpt(s): The present invention relates to anti-human stromelysin monoclonal antibodies, an enzyme immunoassay using such monoclonal antibodies, and a method for the diagnosis of rheumatoid arthritis by determination, on the basis of said immunoassay, of the amount of human stromelysin present in samples as the sum of the amount of latent stromelysin and that of active stromelysin. Stromelysin, also called proteoglycanase or MMP-3 (matrix metalloproteinase-3), is a substance produced in fibroblasts or tumor cells stimulated by different cytokines, growth factors, etc. In the live body, it is present in blood or synovial fluids, besides being produced locally in joints of patients with rheumatoid arthritis. Stromelysin has been considered to play an important role in the intraarticular cartilage destruction in patients with rheumatoid arthritis since it decomposes gelatin, laminin, type IV collagen, fibronectin etc. in
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addition to proteoglycan and type IX collagen, both being important extracellular matrices for articular cartilage. Web site: http://www.delphion.com/details?pn=US05834212__ •
Benzoylecgonine or benzoylnorecgonine as active agents for the treatment of rheumatoid arthritis Inventor(s): Somers; Lowell (16630 Mountain View Rd., Desert Hot Springs, CA 92240) Assignee(s): none reported Patent Number: 4,512,996 Date filed: February 29, 1984 Abstract: Pharmaceutical formulation containing benzoylecgonine and/or benzoylnorecgonine and their use in the treatment of rheumatoid arthritis are disclosed. Excerpt(s): This invention relates to pharmaceutical compositions and dosage forms and their use in the treatment of chronic disease. More particularly, it concerns pharmaceutical compositions and dosage forms and their use in the treatment of the pain and locomotor dysfunction of rheumatoid arthritis. Rheumatoid arthritis is a serious, often crippling, disease characterized by pain and locomotor dysfunction. As pointed out by Nickander et al in their article "Nonsteroidal Antiinflammatory Agents" which appeared at Ann. Rev. Pharmacol. Toxical., 1979, 19:469-90, this sort of pain and locomotor dysfunction are among man's most common and frustrating afflictions. The gravity of this disease has led to the investigation and/or adoption of a wide range of drugs for its alleviation. Aspirin has been commonly used since the turn of this century. Other major drugs for arthritis have historically included indomethacin, other salicylates, phenylbutazone, steroids and gold. While more recently, fenoprofen, ibuprofen, naproxen, sulindac and tolmetin have been approved for use in the United States. While these compounds can offer antiinflammatory, antipyretic and analgesic effects and have proven helpful in the management of rheumatoid arthritis in many patients, when combined with other modalities such as proper rest, exercise, physical therapy and surgery, they are less than ideal. Many exhibit serious side-effects with many patients, particularly gastrointestinal damage and renal toxicity. Each of these materials have the failing of being far from universal--some patients will respond to one material while others respond favorably only to others. Web site: http://www.delphion.com/details?pn=US04512996__
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Benzoylecgonine, benzoylnorecgonine and ecgonine as active agents for the treatment of rheumatoid arthritis and osteoarthritis Inventor(s): Somers; Lowell M. (46861 Madison, Indio, CA 92201) Assignee(s): none reported Patent Number: 4,556,663 Date filed: August 31, 1984 Abstract: Pharmaceutical preparations containing benzoylecgonine, benzoylnorecgonine, and ecgonine are disclosed for treatment of rheumatoid arthritis, and in case of benzoylecgonine and benzoylnorecgonine for the treatment of osteoarthritis as well. The pharmaceutical preparations containing the active
Patents 363
compounds are administered to human patients in effective amounts orally, through inhalation, transdermally or through the mucosal membranes. Excerpt(s): This invention relates to pharmaceutical compositions, dosage forms and their use in the treatment of chronic disease. More particularly, it concerns pharmaceutical compositions and dosage forms and their use in the treatment of the pain and locomotor dysfunction of rheumatoid arthritis, and osteoarthritis. Rheumatoid arthritis is a serious, often crippling, disease characterized by pain and locomotor dysfunction. As pointed out by Nickander et al in their article "Nonsteroidal Antiinflammatory Agents" which appeared at Ann. Rev. Pharmacol. Toxicol., 1979, 19:469-90, this sort of pain and locomotor dysfunction are among man's most common and frustrating afflictions. The gravity of this disease has led to the investigation and/or adoption of a wide range of drugs for its alleviation. Aspirin has been commonly used since the turn of this century. Other major drugs for arthritis have historically included indomethacin, other salicylates, phenylbutazone, steroids and gold. While more recently, fenoprofen, ibuprofen, naproxen, sulindac and tolmetin have been approved for use in the United States. While these compounds can offer antiinflammatory, antipyretic and analgesic effects and have proven helpful in the management of rheumatoid arthritis in many patients, when combined with other modalities such as proper rest, exercise, physical therapy and surgery, they are less than ideal. Many exhibit serious side effects with many patients, particularly gastrointestinal damage and renal toxicity. Each of these materials have the failing of being far from universal--some patients will respond to one material while others respond favorably only to others. Web site: http://www.delphion.com/details?pn=US04556663__ •
Biological treatment for rheumatoid arthritis Inventor(s): Smith; J. Bruce (Philadelphia, PA), Fort; John G. (Philadelphia, PA) Assignee(s): Thomas Jefferson University (Philadelphia, PA) Patent Number: 5,723,503 Date filed: September 28, 1994 Abstract: A method of treating rheumatoid arthritis is provided which involves administering an effective amount of allogeneic mononuclear cells or a molecule derived from these cells to an individual having rheumatoid arthritis. Also provided are compositions for the treatment of rheumatoid arthritis. Excerpt(s): Tens of millions of people in the United States suffer from rheumatoid arthritis (RA) or a related disease. While arthritis results in significantly fewer deaths as compared to cancer and cardiovascular diseases, there is no other group of diseases that causes so much suffering in so many people for such a prolonged period of time. Because of the tendency to disable and even permanently cripple individuals suffering from arthritis, this group of diseases is extremely important both socially and economically. There is presently no satisfactory cure for rheumatoid arthritis because its cause is unknown. In addition, many of the therapeutic agents administered to alleviate pain and inflammation associated with the disease, such as disease-modifying antirheumatic drugs (DMARDs) and non-steroidal anti-inflammatory agents (NSAIDs), produce intolerable side effects. The understanding of the RA disease process has been considerably enhanced by the application of molecular immunology techniques. It is now generally accepted that rheumatoid arthritis represents a multifactorial disease with environmental factors (infectious agents or toxins), genetic susceptibility, and
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immune or autoimmune responses playing inter-connected roles. After initiation of the disease process, it is believed that activated T cells and their products are responsible for the progressive destruction of articular cartilage and sub-chondral bone that is characteristic of rheumatoid arthritis. Advances in the understanding of the immunopathogenesis of rheumatoid arthritis have been coupled with immunologic strategies for treatment. Immunologic approaches to the treatment of rheumatoid arthritis are important and desirable given the potential toxicities associated with most remittive therapy in use today and the continued poor prognosis of rheumatoid arthritis despite aggressive drug treatment. Web site: http://www.delphion.com/details?pn=US05723503__ •
Collagen mimetic and method of treating rheumatoid arthritis using same Inventor(s): Braswell; A. Glenn (6100 Lake Forest Dr., NE., Suite 400, Atlanta, GA 30328), Ahmed; Aftab J. (Marina Del Ray, CA) Assignee(s): Braswell; A. Glenn (Atlanta, GA) Patent Number: 5,849,323 Date filed: June 12, 1997 Abstract: A collagen mimetic peptide having the nine amino acid sequence glycineproline-hydroxyproline-glycine -proline-glutamine-glycine-methionine-glycine, and analogs thereof is described. The collagen mimetic peptide may be included within a pharmaceutical composition also containing a pharmaceutically acceptable carrier and/or animal tissue. The collagen mimetic peptide is used in a treatment of rheumatoid arthritis by orally administering the collagen mimetic in an amount effective to reduce or alleviate one or more symptoms associated with rheumatoid arthritis. Excerpt(s): This invention relates to a specific collagen mimetic peptide, pharmaceutical compositions containing the peptide, and a method of treating rheumatoid arthritis through the oral administration of the peptide and/or pharmaceutical composition. Rheumatoid arthritis is an autoimmune disease wherein the immune system of the body mistakenly perceives the body's own collagen as foreign and mounts an abnormal immune response against it. Rheumatoid arthritis is characterized by persistent swollen and inflamed joints, and progresses into the destruction of cartilage and the erosion of bone, ultimately leading to destruction of joints. Collagen, in particular Type II collagen, is a major component of cartilage that is particularly affected. Known treatments for arthritis have involved the use of nonspecific immunosuppressive drugs which suppress the entire immune system and are incapable of selectively suppressing the abnormal autoimmune response. This restraint of the immune system also increases the risk of infection. In addition, prolonged use of such drugs can entail severe toxic side effects. Moreover, such immunosuppressive drugs are only partially effective in mitigating symptoms of rheumatoid arthritis, and this partial effectiveness greatly decreases even more over time. Web site: http://www.delphion.com/details?pn=US05849323__
Patents 365
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Combination therapy for rheumatoid arthritis Inventor(s): Ridolfo; Anthony S. (Zionsville, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 4,355,029 Date filed: June 1, 1981 Abstract: A therapeutic method for treating rheumatoid arthritis in which benoxaprofen plus aspirin are administered once a day and aspirin alone three times a day, all dosages being given at six hour intervals. Excerpt(s): This invention provides a novel treatment method for rheumatoid arthritis and other related inflammatory conditions, utilizing combination drug therapy in part, such as a combination of benoxaprofen, a lipoxygenase inhibitor, and a cyclo-oxygenase inhibitor such as aspirin. According to my invention, patients suffering from rheumatoid arthritis are administered from 200 to 800 milligrams of benoxaprofen and from 325 to 1170 of aspirin once a day and then at 6 hour intervals during the remainder of the 24 hour period from 325 to 1170 milligrams of aspirin alone. Preferably, the rheumatoid arthritis patient is given 600 mg. of benoxaprofen plus 975 milligrams (15 grains) of aspirin once a day and 975 milligrams of aspirin alone at 6 hour intervals. The regimen is then repeated on a daily basis. The basis for the enhanced therapeutic effect from my novel process is the use of drugs acting at different sites of the inflammatory process. Improvement occurs even though blood levels of benoxaprofen are decreased with the concomitant addition of aspirin. It is an advantage of this invention that in the combination of a lipoxygenase inhibitor such as benoxaprofen and a cyclo-oxygenase inhibitor, each drug can be employed at dose levels lower than the commonly accepted effective dose for the individual drug. Benoxaprofen, 2-(2-p-chlorophenyl-5benzoxazolyl)propionic acid, is disclosed in Example 2 of U.S. Pat. Re No. 29,608 reissued April 11, 1978. Web site: http://www.delphion.com/details?pn=US04355029__
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Compositions, methods and kits for treating rheumatoid arthritis Inventor(s): Albert; Daniel A. (Philadelphia, PA) Assignee(s): Super Gen, Inc. (Dublin, CA) Patent Number: 6,362,176 Date filed: July 20, 2000 Abstract: Disclosed are methods of treating rheumatoid arthritis by coadministering synergistic effective amounts of pentostatin and methotrexate to a host in need thereof, and kits and compositions that include pentostatin and methotrexate. Excerpt(s): This invention relates to treatment of rheumatoid arthritis through coadministration of pentostatin and methotrexate and analogs and derivatives thereof. Rheumatoid arthritis (RA) is a systematic inflammatory condition that results in swelling, pain, loss of motion, and tenderness of target joints throughout the body. RA is characterized by chronically inflamed synovium that is densely crowded with lymphocytes. The synovial membrane, which is typically one cell layer thick, becomes intensely cellular and assumes a form similar to lymphoid tissue, thus including vessels, dendritic cells, T, B, and NK cells, macrophages, and clusters of plasma cells. Additionally, there is often a plethora of immunopathological mechanisms at work,
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including antigen-antibody complexes, polymorphonuclear neutrophils, inflammatory T cells, and activated macrophages. Eventually, these processes result in destruction of the integrity of the joint, resulting in deformity and permanent loss of function. A more detailed description of the etiology and physiology of RA can be found in Zvaifler, N., "Etiology and Pathogenesis of Rheumatoid Arthritis in Arthritis and Allied Conditions" 659-73 (ed. D. M. McCarty). This document, and all other documents or references, cited to herein are incorporated by reference as if reproduced completely herein. Rheumatoid arthritis is a common disease affecting 1 to 2% of the world's population with a female to male predominance of 3-4:1. The peak incidence is in the third to fourth decade. Once acquired the disorder is chronic; therefore the prevalence of the disease increases as one examines increasing age groups. The disease is of unknown cause, although genetics may impact the risk of developing rheumatoid arthritis. Although it is not certain, some common infection or infections might trigger the autoimmune process in susceptible individuals. Environmental influences are not thought to play a major role in the development of the disease. Interestingly, exogenous estrogens in the form of BCPS appear to reduce the risk. Web site: http://www.delphion.com/details?pn=US06362176__ •
Diagnosing autoimmune rheumatoid arthritis by measuring proteolytic activity of.alpha.sub.2 -macroglobulin Inventor(s): Spear; Gregory T. (Forest Park, IL), Skosey; John L. (Chicago, IL), Gaspar; Alexander M. (Chicago, IL), Ganea; Doina (Elmhurst, IL), Teodorescu; Marius C. (Westchester, IL) Assignee(s): University of Illinois, Board of Trustees (Urbana, IL) Patent Number: 4,499,186 Date filed: December 30, 1982 Abstract: A method for diagnosis of rheumatoid arthritis and related autoimmune diseases comprises blocking calcium ions contained in a blood sample, effecting hydrolysis of a selected substrate in the presence of.alpha.sub.2 -macroglobulin (.alpha.sub.2 M) from the blood sample, and determining the extent of hydrolysis of the substrate. Preferably,.alpha.sub.2 M in plasma is incubated with a hydrolyzable chromogenic substrate and the liberated chromogen is determined spectrophotometrically. A diagnostic kit is also provided. Excerpt(s): The invention described herein was made in the course of work supported in part by NCI Grant CA 21399 and in part by NIH Grant AM 28469. It is well-known that some diseases have an autoimmune pathogenetic mechanism. Among these are rheumatoid arthritis, systemic lupus erythematosus, and chronic active hepatitis. A general increase in the level of gammaglobulins (antibodies) often accompanies an increase in the level of a particular antibody or antibodies in patient serum. These observations have led to the suggestion that polyclonal (general) activation of Blymphocytes is involved in the disease process and might even precede the emergence of a particular antibody. For example, in rheumatoid arthritis the symptoms may appear before the characteristic antibody, i.e., the rheumatoid factor, develops. On the other hand, other arthritides are known to have no systemic autoimmune basis and are commonly described as "sero-negative". These include Reiter's syndrome, ankylosing spondylitis, psoriatic arthritis, osteo-arthritis, and gout. Web site: http://www.delphion.com/details?pn=US04499186__
Patents 367
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Diagnostic technique for rheumatoid arthritis Inventor(s): Chang; Jin-Lai (1648 Gilberto Dr., Glendale Heights, IL 60137), Skosey; John L. (4932 S. Kimbark, Chicago, IL 60615), Teodorescu; Marius C. (10547 Essex, Westchester, IL 60153) Assignee(s): none reported Patent Number: 4,402,934 Date filed: October 30, 1980 Abstract: A method for diagnosis of rheumatoid arthritis and related diseases comprises determination of polyclonal lymphocyte activation in B-cells cultured in the presence of patient serum. A diagnostic kit is also provided. Excerpt(s): Rheumatic diseases affect a significant proportion of the population, crippling many people and having only a palliative treatment at best. Diagnosis of rheumatic diseases is difficult and uncertain, and many patients escape classification until the disease has progressed to a stage where serious damage is evident. The classification of the different rheumatic diseases, including rheumatoid arthritis, is based on both clinical and laboratory data, and the same criteria are used to determine the efficiency of any selected treatment. In all of the rheumatic diseases, the common denominator is an abnormal function of the immune system. This abnormal function is suggested by the appearance of antibodies against a patient's own structures and also by the beneficial effect of immunosuppressive or cytotoxic drugs which destroy cells involved in the immune mechanisms. It has been shown that in some of these diseases the B-cells that produce antibodies are overactive, and produce antibodies against a variety of antigens, including some to which they may not have been previously exposed. Another relatively common feature is the increase in the serum immunoglobulin with polyclonal character. From such observations, it has been ascertained that B-cells programmed to produce antibodies against self antigens are present in normal individuals. It has likewise been suggested that polyclonal B-cell activation may be the cause of some autoimmune diseases. Despite such studies of rheumatic diseases, there remains a critical need for a diagnostic technique capable of providing, with suitable certainty, an early diagnosis of the incidence of such diseases. This is especially true of the crippling diseases, such as, particularly, rheumatoid arthritis. Web site: http://www.delphion.com/details?pn=US04402934__
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Drug for the treatment of rheumatoid arthritis Inventor(s): Okumura; Ko (Chiba, JP), Miyake; Sachiko (Tokyo, JP), Nishida; Tadashi (Osaka, JP), Yagita; Hideo (Tokyo, JP) Assignee(s): Kanebo, Ltd. (Tokyo, JP) Patent Number: 5,855,888 Date filed: October 17, 1996 Abstract: A drug for the treatment of rheumatoid arthritis, which comprises as an active ingredient a monoclonal antibody which recognizes specifically extracellular region of human VLA-2. Preferable drug for the treatment of rheumatoid arthritis comprises as an active ingredient a monoclonal antibody which recognizes specifically extracellular region of human VLA-2,.alpha. chain. The above drug for the treatment of rheumatoid
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arthritis can suppress swelling due to arthritis in rheumatoid arthritis with low toxicity and hence is useful for the treatment of rheumatoid arthritis. Excerpt(s): This application is a 371 of PCT/JP95/00527 filed Mar. 22, 1995. This invention relates to a drug for the treatment of rheumatoid arthritis which comprises as an active ingredient a monoclonal antibody which can specifically recognize extracellular region of human VLA-2. Rheumatoid arthritis (hereinafter, abbrebiated as "RA") is a chronic inflammatory disease which shows an inflammatory symptom mainly in the articular synovial membrane, where various inflammatory cells permeate into synovial fluid through hemangioendotheliocytes of synovial membrane. It is assumed that the pathological symptoms may be participated by immunological mechanism, and the symptoms may become a trigger of immuno-response, but it is still difficult to specify the mechanism. It is also important to make clear the reason why the inflammatory symptoms are maintained at the synovial membrane even after the cause of the disease has been removed. A series of processes of these inflammation symptoms, particularly chronicity and duration thereof, will be deeply participated by lymphocytes which take charge of immunization. Web site: http://www.delphion.com/details?pn=US05855888__ •
Free fatty acids for treatment or propyhlaxis of rheumatoid arthritis arthritis Inventor(s): Rubin; David (San Diego, CA) Assignee(s): Century Laboratories, Inc. (Port Washington, NY) Patent Number: 4,843,095 Date filed: August 7, 1987 Abstract: Free fatty acids form fish oil, DHA and EPA, are useful in treating rheumatoid arthritis. The free fatty acids were an order of magnitude more effective in treating arthritis than unhydrolyzed fatty acids derived from fish oil. Excerpt(s): The present invention relates to the use of free fatty acids which can be used to treat or provide effective prophylaxis against rheumatoid arthritis. Rheumatoid arthritis is a serious, often crippling, disease characterized by pain and locomotor dysfunction. This sort of pain and dysfunction are among the most common and frustrating afflictions. The gravity of this disease has led to the investigation and/or adoption of a wide range of drugs for its alleviation. Aspirin has been commonly used since the turn of this century. Other major drugs used to treat arthritis include indomethacin, other salicylates, phenylbutazone, steroids, and gold. Other compounds which have been used to treat arthritis are fenoprofen, ibuprofen, naproxen, sulindac, and tolmetin. While the known compounds can offer anti-inflammatory, antipyretic, and analgesic effects, and have proven helpful in the management of rheumatoid arthritis in many patients, when combined with other modalities such as proper rest, exercise, physical therapy, and surgery, they are less than ideal. Many of these medications exhibit serious side effects with many patients, particularly gastrointestinal damage and renal toxicity. None of these materials is universally useful in treating rheumatoid arthritis, as some patients will respond to one material while others respond favorably only to others. Web site: http://www.delphion.com/details?pn=US04843095__
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Heteroaroyl 10-deazaamino-pterine compounds and use for rheumatoid arthritis Inventor(s): Colwell; William T. (Menlo Park, CA), Piper; James R. (Birmingham, AL), DeGraw; Joseph I. (Sunnyvale, CA), Smith; R. Lane (Palo Alto, CA), Sirotnak; Francis M. (New York, NY) Assignee(s): SRI International (Menlo Park, CA) Patent Number: 5,354,751 Date filed: July 12, 1993 Abstract: There is disclosed certain heteroaroyl 10-deazaaminopterin and 5, 10 and 8, 10 di deazaminopterin compounds and their use for treatment of rheumatoid arthritis and related diseases and preparative process.Also disclosed are 10 alkenyl-(and alkynyl) 10deazaminopterins also disclosed for treatment of rheumatoid arthritis and for leukemia and ascites tumors and preparative process. Excerpt(s): The current invention concerns novel antiinflammatory and antineoplastic 10-deazaaminopterin compounds. In particular, the invention concerns heteroaroyl-10deazaaminopterins and 10-alkenyl or 10-alkynyl-10-deazaaminopterins having pronounced antiinflammatory activity, antileukemic and antitumorigenic activity, as well as a method for treatment of inflammatory diseases, leukemia and tumors. Pharmaceutical compositions containing these heteroaroyl-10-deazaaminopterin compounds are also disclosed. The invention further concerns a process for preparation of these compounds. Rheumatoid arthritis, malignant tumors and leukemia are severely debilitating diseases which are often fatal, as in cases of leukemia and malignant growths. Drugs which are currently available and used for treatment of these diseases typically have unpleasant secondary symptoms or are highly toxic. Rheumatoid arthritis is one of a number of forms of proliferative disease, and the development of drugs for amelioration or curing the disease has occupied the attention of research organizations for many years, until most recently without appreciable success. Web site: http://www.delphion.com/details?pn=US05354751__
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HLA-DRBI peptides with specific binding affinity for HLA-DQ molecules: prevention and treatment of rheumatoid arthritis Inventor(s): Luthra; Harvinder S. (Rochester, MN), David; Chella S. (Rochester, MN), Zanelli; Eric (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 5,965,787 Date filed: August 31, 1995 Abstract: Disclosed are transgenic mice carrying a human HLA-DQ sgene. The transgenic mice are deficient in mouse H-2 class II molecules. Such mice provide animal model systems to identify peptides useful for preventing or treating rheumatoid arthritis. Also disclosed are methods and materials for treating rheumatoid arthritis, including administration of peptides having specific binding affinity for HLA-DQ molecules expressed in a rheumatoid arthritis patient. Excerpt(s): Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis leading to destruction of joints and, sometimes, to severe systemic complications such as vasculitis, amyloidosis or Felty's syndrome. It is widely accepted that a strong genetic component contributes to the susceptibility or resistance to certain human autoimmune diseases
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such as RA. Attempts to identify the particular genes involved in these disorders has been an area of major focus for many laboratories. Among the numerous genes studied, those encoding the class I and class II molecules of the human leukocyte antigen (HLA) complex have garnered particular attention. The primary function of HLA-class I and class II molecules is binding and presentation of processed antigenic peptides to T cells bearing receptors specific for particular HLA-peptide complexes. The presentation event plays a pivotal role in shaping the cellular immune repertoire and in shaping the nature and scope of the immune response against a given antigen. In Caucasians, genetic studies initially showed a high prevalence of certain HLA DR subtypes among RA patients. Specifically, predisposition to RA has been linked to the class 30 II HLA-DRB1 locus, and in particular to the DR4 specificity. Within the HLA-DR4 specificity, the Dw4 (DRB1*0401), Dw14 (DRB1*0404/0408), and Dw15 (DRB1*0405) subtypes confer genetic predisposition to RA, while the Dw10 (DRB1*0402) subtype does not confer such genetic predisposition. Nepom et al., Ann. Rev. Immunol. 9: 493-525 (1991); Wordsworth et al., Proc. Natl. Acad. Sci. USA 86: 10049-53 (1989); Ollier et al., Rheum. Dis. Clin. North. Am. 18: 741-59 (1992). Several studies have also shown that the incidence of RA is significantly decreased in patients expressing HLA-DR2 alleles compared with normal controls. Jaraquemada et al., Ann. Rheum. Dis. 45: 627-36 (1986); Deighton et al., Br. J. Rheumatol. 32: 893-98 (1993); Ollier et al., cited supra. Indeed, the DR2Dw12 subtype is associated with a low incidence of RA in the Japanese population. Ohta et al., Human Immunol. 5: 123-32 (1982). For a general review of HLA nomenclature, see Bodmer et al., Tissue Antigens 44: 1-18 (1994), incorporated herein by reference. A further caveat regarding studies aimed at identifying the precise HLA-D region gene responsible for susceptibility to RA is the presence of certain DQB alleles in linkage disequilibrium with particular HLA-DR genes. Such linkages further constrain any conclusions concerning the relative impact of particular HLA-D region genes on RA susceptibility. For example, two allelic forms of DQB, HLA-DQ7 and HLA-DQ8, are associated with the HLA-DR4 genotype in RA susceptibility. Gregersen et al., cited supra; Singal et al., Lancet 2: 111820 (1987); Lanchbury et al., Human Immunol. 26: 59-71 (1989). Moreover, an interesting, albeit small, study analyzing Indian patients with RA showed that 100% possessed the HLA-DQ8 allele, versus 33.3% for the normal subjects. Taneja, Rheumatol. Int. 11: 251-55 (1992). Thus, despite an association of the "Shared Epitope" with RA susceptibility, prior studies have also pointed to a possible role for HLA-DQ alleles in this disease. Web site: http://www.delphion.com/details?pn=US05965787__ •
Human phospholipase activating protein and methods for diagnosis of rheumatoid arthritis Inventor(s): Bomalaski; John S. (11 Chestnut La., Wayne, PA 19087), Clark; Mike A. (15 Westmore Dr., Denville, NJ 07835), Shorr; Robert (36 Overbrook Pky., Wynnewood, PA 19096) Assignee(s): none reported Patent Number: 5,367,063 Date filed: November 4, 1993 Abstract: The invention provides methods for detecting elevated levels of phospholipase A.sub.2 activating protein in persons suspected of having rheumatiod arthritis to thereby indicate the presence of rheumatoid arthritis in the person comprising the steps of providing a sample of body fluid or tissue from said person; contacting the sample with an antibody specific for phospholipase A.sub.2 activating protein such that the
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antibody binds with phospholipase A.sub.2 activating protein in the sample; detecting the antibody thereby indicating the presence of phospholipase A.sub.2 activating protein, whereby elevated levels of phospholipase A.sub.2 activating protein in the sample as compared with levels found in persons not having rheumatoid arthritis indicates the presence of rheumatoid arthritis in the person. Kits and reagents for detecting rheumatoid arthritis are also provided. Excerpt(s): The present invention relates to the field of methods for diagnosing rheumatoid arthritis. More particularly the present invention relates to methods for diagnosing rheumatoid arthritis using immunoassays. Rheumatoid arthritis is the best known form of arthritic disease, affecting millions of patients worldwide. It is characterized by a progressive inflammation of joints and internal organs by immunocompetent cells and destructin of articular cartilage resulting in progressive morbidity and death. Prostaglandins and related eicosanoids are thought to be important mediators of these immune and inflammatory responses. Increased quantities of eicosanoids are produced by rheumatoid synovium in both organ and cell culture and are found in elevated levels in rheumatoid synovial fluid and from peripheral blood cells of affected patients. Clinical evidence suggests that early diagnosis and intervention with cytotoxic and immunomodulatory agents is essential to altering the course of the disease. Phospholipase A.sub.2 (PLA.sub.2) is a lipolytic enzyme which hydrolyzes the 2-acyl fatty acid ester of glycerophospholipids, thus releasing arachidonic acid. Arachidonic acid has been shown to be converted into a number of biologically active compounds known as eicosanoids. PLA.sub.2 activity has been shown to be ubiquitous and to reside in several different gene products. Both membrane bound and soluble forms of the enzyme have been described. Extracellular secretion of soluble PLA.sub.2 was first described in 1980. Circulating PLA.sub.2 was implicated in endotoxin shock and has since been implicated in acute and chronic inflammatory reactions. Web site: http://www.delphion.com/details?pn=US05367063__ •
Immunoassays for measuring the avidity of rheumatoid factor in rheumatoid arthritis Inventor(s): Newkirk; Marianna M. (Pierrefonds, CA) Assignee(s): McGill University (Montreal, CA) Patent Number: 5,679,537 Date filed: October 26, 1994 Abstract: The present invention relates to a novel immunoassay for measurement of rheumatoid factors (RFs) avidity for correlation with rheumatoid arthritis disease activity and for the presence of the different glycoforms of IgG. Excerpt(s): The invention relates to a novel ELISA immunoassay for measurement of rheumatoid factors (RFs) avidity for possible correlation with rheumatoid arthritis disease activity and for the presence of the different glycoforms of IgG. Rheumatoid factors (RF) have long been suspected to play a role in the pathogenesis of rheumatoid arthritis (RA), as they are detected in up to 70% of RA patients and are sustained at high titers for years. Their association with the pathogenic changes have been controversial, and indeed they are found in normal individuals generally in low titers and in patients with mixed cryoglobulinemia frequently in high titers, who lack the synovitis characteristic of RA. In the past decade, since the discovery of an imbalance of the different glycoforms of IgG in patients with RA, much research has focused on the
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possible consequences of one of the glycoforms of IgG, namely the Gal(0) form. Since the oligosaccharide chain on IgG resides in between the two gamma-2 domains, it has been postulated that changes in the structure such as the absence of the terminal sialic acid and galactose ›gal(0)! could affect the binding of RFs since it is thought that they bind in the cleft between the gamma-2 and gamma-3 domains. It has been found that, whereas some purified monoclonal RFs bound maximally to IgG when the oligosaccharide chain was intact (Newkirk, M. M. et al., 1993, J. Rheumatol., 20:776), other RFs bound even when the oligosaccharide was altered or removed (Newkirk, M. M. et al., 1990, Arthritis Rheum., 33:800). These previous studies have all had the short coming that it was not known, which, if any, of the monoclonal antibodies studied, could be correlated with any pathogenic role. Web site: http://www.delphion.com/details?pn=US05679537__ •
Immunodiagnostic assay for rheumatoid arthritis Inventor(s): Stanworth; Dennis Raymond (Birmingham, GB2), Lewin; Ian Victor (Tamworth, GB2), Nayyar; Sarita (Penn, GB2) Assignee(s): Peptide Therapeutics Limited (Cambridgeshire, GB2) Patent Number: 5,827,668 Date filed: August 10, 1995 Abstract: The assay of rheumatoid arthritis by reference to IgA-.alpha.sub.1 antitrypsin complex present in analytes is facilitated by certain novel antibody reagents. These are ligands comprising an antibody domain specific for an antigenic determinant of a complex of human IgA and.alpha.sub.1 -antitrypsin, this antibody domain being substantially non reactive with free human IgA and free human.alpha.sub.1 -antitrypsin. Monoclonal antibodies to the naturally occurring IgA-.alpha.sub.1 AT complex and monoclonal or polyclonal antibodies to a synthetic peptide are preferred. The synthetic peptide in itself part of the invention and preferably has an amino acid sequence: ValSer-Val-Val-Met-Ala-Glu-Val-Asp-Gly-Thr-Cys-Tyr (SEQ ID NO:2) Excerpt(s): The present invention is directed to a method of assay of rheumatoid arthritis (RA). More particularly, the present invention is directed to the assay of human immunoglobulin A-.alpha.sub.1 -antitrypsin complex (IgA-.alpha.sub.1 AT) in patients who are suspected of having or are being treated for RA. Rheumatoid arthritis has been described as an unresolved systemic inflammation in which immune dysfunction and genetic susceptibility play roles. In earlier stages, it is often characterised by fluctuating remissions and exacerbations, and in later stages by a chronic granulatamous response (pannus formation) leading to tissue destruction notably of bone and cartilage. The synovial membrane in RA has many of the characteristics of a hyperactive immunologically stimulated lymphoid organ and the ratio of T suppressor to T helper lymphocytes has been shown to be significantly reduced. wherein diagnosis of 3 or 4 of these factors is considered representative of probable RA and diagnosis of 5 or more of the factors is considered representative of definite RA. Web site: http://www.delphion.com/details?pn=US05827668__
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Isolated nucleotide sequences associated with multiple sclerosis or rheumatoid arthritis and a process of detecting Inventor(s): Komurian-Pradel; Florence (Saint Cyr au Mont d'Or, FR), Jolivet-Reynaud; Colette (Bron, FR), Bedin; Frederic (Lyons, FR), Perron; Herve (Lyons, FR), Mandrand; Bernard (Villeurbanne, FR), Beseme; Frederic (Villefontaine, FR), Paranhos-Baccala; Glaucia (Lyons, FR) Assignee(s): Bio Merieux (Marcy l'Etoile, FR) Patent Number: 6,582,703 Date filed: November 26, 1997 Abstract: The invention provides viral material and nucleotide fragments associated with multiple sclerosis and/or rheumatoid arthritis for use in methods of diagnosis, prophylaxis, and therapy. Excerpt(s): Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), the cause of which remains as yet unknown. Many studies have supported the hypothesis of a viral aetiology of the disease, but none of the known viruses tested has proved to be the causal agent sought: a review of the viruses sought for several years in MS has been compiled by E. Norrby (1) and R. T. Johnson (2). The discovery of pathogenic retroviruses in man (HTLVs and HIVs) was followed by great interest in their ability to impair the immune system and to provoke central nervous system inflammation and/or degeneration. In the case of HTLV-1, its association with a chronic inflammatory demyelinating disease in man (48) led to extensive investigations to search for an HTLV1-like retrovirus in MS patients. However, despite initial claims, the presence of HTLV-1 or HTLV-like retroviruses was not confirmed. Web site: http://www.delphion.com/details?pn=US06582703__
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Method for administration of azauridine and pyridoxine for the treatment of rheumatoid arthritis Inventor(s): Drell; William (San Diego, CA) Assignee(s): UR Labs, Inc. (San Diego, CA) Patent Number: 5,389,617 Date filed: November 12, 1993 Abstract: A method for treating patients with rheumatoid arthritis comprises administering azaribine to the patient at a dosage level of 10 to 50 mg/kg/day for an initial period of from about 1 to about 3 weeks and then administering azaribine to the patient at dosage levels of at least 50 mg/kg/day and preferably at least 100 mg/kg/day. Excerpt(s): This invention relates to the treatment of rheumatoid arthritis and more particularly to a method for administering, 6-azauridine, azaribine or other 6-azauridine compound for treating rheumatoid arthritis. Azaribine (2', 3', 5'-triacetyl-6-azauridine) has been found to be effective in oral dosage form for the treatment of psoriasis, psoriatic arthritis, mycosis fungoides, herpes simplex, and small pox. Typical dosage levels for the treatment of such conditions are 125 to 250 mg/kg/day. It has been found that such a dosage level may be given for many weeks without side effects, particularly when administered in combination with pyridoxine or other pyridoxine compound, such as pyridoxal phosphate. At high doses, azaribine demonstrates anti-inflammatory
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properties. For this reason, azaribine has been tested for the treatment of rheumatoid arthritis. However, at dosage levels of azaribine of 100 mg/kg/day or higher given to patents with rheumatoid arthritis, severe side effects have been reported including fever, joint pain, joint swelling, edema, nausea, emesis, exanthema, painful and rigid muscles and depression. Elis and Raskova, "New Indications for 6-Azauridine Treatment in Man, A Review," Europ.J.Clin. Pharmacol. 4, 77-81 (1972); Elis, Slavik, Ruskova, "Side Effects of 6-Azauridine triacetate in Rheumatoid Arthritis," Clin. Pharmacol. & Therap., II., 404-407 (1970) It has further been reported that slight side effects were produced even at dosage levels of 50 mg/kg per day. Ruskova, Elis, Perlik, Polansky and Slavik, "Unexpected Side Effects of 6-Azauridine in Rheumatoid Arthritis and Feedback in Animal Experiments," Proc. Soc. Europ for the Study of Drug Toxicity," Upsala: June 1970, 12 191 (1971). It is believed that for this reason, no work has been done on this indication for the last 20 years. Web site: http://www.delphion.com/details?pn=US05389617__ •
Method for detecting bacteria in urine and for treating rheumatoid arthritis, essential hypertension and other diseases associated with bacteriuria Inventor(s): Hyman; Edward S. (3420 Jefferson Ave., New Orleans, LA 70125) Assignee(s): none reported Patent Number: 4,673,637 Date filed: April 23, 1984 Abstract: A novel method of urine specimen preparation comprising intense centrifugation and a lipid wash mitigates or prevents loss of bacteria-containing sediment prior to examination. Modifications of the method facilitate examination of urines with interfering constituents such as glucose, phosphates, and soluble and insoluble proteins. By this method, bacteria have been found in the urine of patients suffering from rheumatoid arthritis and essential hypertension. These bacteria were not detected in standard urine preparations. Administration of antibiotic agents effective against the bacteria detected, such as clindamycin, destroyed these bacteria and provided therapeutic relief. Excerpt(s): This invention relates to a new method of detecting abnormal levels of bacteria in urine, and to new methods for the treatment of patients suffering from rheumatoid arthritis, essential hypertension, and other diseases in which significant bacteriuria was detected by the novel specimen preparation of the present invention that would not have been easily demonstrated by known procedures. The direct microscopy and the culture methods each have pitfalls In the past 20-25 years the direct visualization of bacteria in urine has largely been abandoned in favor of the methods involving culturing and counting the colonies of bacteria. Indeed virtually all of the studies of the significance of bacteriuria are based upon culturing the urine, and the direct microscopic examination of urine has been relegated to the status of a quick but inadequate screening procedure which may be helpful because it can be correlated with the culture methods. Rheumatoid arthritis (RA) is a chronic inflammation of the joints, generally regarded as a systemic autoimmune disorder. Its etiology is unknown, but it has been postulated that it is associated with microbial infection. See, e.g., D. C. Demonde, ed., Infection and Immunity in the Rheumatic Diseases, 95-287 (Blackwell Scientific Publications, London: 1976). The evidence, however, until the present discovery, was inconclusive. See, e.g., D. J. McCarty, et al., ed., Arthritis and Allied Conditions: A Textbook of Rheumatology, ch 28 at 417 (9th ed. 1979); R. G. Petersdorf, et
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al., ed., Harrison's Principles of Internal Medicine, Part Six, Chapter 346, at 1977 (McGraw Hill: 1983). Bacteriuria has not been associated with RA, and indeed one authority remarks "Urinary abnormalities are relatively uncommon in RA. Urinary tract infection was not found to be increased in RA patients." McCarty, supra, chapter 33, page 499, citing Ann. Rheum. Dis., 27: 345 (1968). Hypertension is a chronic elevation of blood pressure resulting from the obstruction of blood flow within the kidney (secondary hypertension) or without apparent cause (essential hypertension). One kidney disorder associated with secondary hypertension is pyelonephritis, the inflammation of the renal pelvis of the kidney as a result of bacterial infection, usually responsive to antibiotics. It has not been reported, however, that there is any correlation between essential hypertension and asymptomatic bacteriuria (bacteriuria observed in patients not reporting symptoms of urinary tract disorders). According to N. M. Kaplan, Clinical Hypertension, 14 (3d. ed. 1982), bacteriuria is found in 2-5% of hypertensives. Most of these positive cultures were of gram-negative rods. The method of the present invention has demonstrated a much higher incidence of bacteriuria in hypertensives, perhaps as high as 90%, and that cocci or "exploded cocci" are found in considerable numbers. Web site: http://www.delphion.com/details?pn=US04673637__ •
Method for determining susceptibility to rheumatoid arthritis Inventor(s): Shiozawa; Shunichi (11-6 Takenodai 2-chome, Nishi-ku, Kobe-shi, Hyogo, 651-2274, JP) Assignee(s): none reported Patent Number: 6,623,924 Date filed: January 31, 2000 Abstract: The application provides genes causative of rheumatoid arthritis, which are located within.+-.1 centimorgan from DNA sequences to which the microsatellite markers D1S214, D1S253, D8S556, DXS1001, DXS1047, DXS1205, DXS1227 and/or DXS1232 are hybridized: a method for diagnosing rheumatoid arthritis, including amplifying the genomic DNA of a subject by PCR using at least one of the microsatellite markers as primer and comparing the PCR products thereof with the PCR products prepared in the same manner using the genomic DNA of a normal control; and a method for identifying the causative factors of rheumatoid arthritis including the same as described above. Excerpt(s): The present invention relates to the genes causative of rheumatoid arthritis, a method for diagnosing rheumatoid arthritis using the mutations of these genes as the indicators, and a method for identifying the causative factors of rheumatoid arthritis. The aspects of arthritis and joint damage causing rheumatoid arthritis, particularly the pathological courses thereof, have been elucidated gradually through various research works. Because many of the autoimmune diseases including rheumatoid arthritis are induced by the concomitant participation of numerous causative factors and are then exacerbated progressively to the stage of apparent diseases, however, the interactive mechanism per se of such numerous factors should be elucidated for accurate characterization and appropriate therapeutic management of the disease. The prevalent rheumatoid arthritis is about 1% (N. Engl. J. Med., 322: 1277-1289, 1990), but the frequency of the disease is about 8 times increased in the siblings of the patients with the disease (Cell, 85: 311-318, 1996). Hence, it is predicted that a certain genetic factor may serve as one of the causative factors. Nevertheless, molecular genetic technology and
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genetic engineering technology for general use for identifying of genetic factors of diseases never function effectively in case of autoimmune diseases, because the onset of autoimmune diseases is never induced via such a biologically simple mechanism as abnormal amplification of one mutated gene as in the case of cancer. Conventional strategies of traditional genetics for the elucidation of the fundamental genetic pathogenesis of diseases have demonstrated distinctively that autoimmune diseases are caused by genetic multi-factor inheritance, but the strategies were apparently insufficient. As has been described above, none of the genes involved in rheumatoid arthritis or none of the loci of the genes on chromosome have absolutely been evidenced so far. Web site: http://www.delphion.com/details?pn=US06623924__ •
Method for diagnosing rheumatoid arthritis Inventor(s): Prakash; Ramesh K. (Salt Lake City, UT) Assignee(s): Theratech, Inc. (Salt Lake City, UT) Patent Number: 5,395,753 Date filed: February 19, 1993 Abstract: A method is described for diagnosing rheumatoid arthritis by providing a recombinant IgM-specific rheumatoid arthritis-associated antigen and detecting antibodies against the antigen in patient sera. Preliminary steps of making a cDNA library from polyadenylated RNA purified from human cells, selecting recombinants that express the antigen, recloning cDNA containing the antigen gene in a high level expression vector, expressing the antigen in transformed cells, and purifying the antigen are also described. Excerpt(s): This invention relates to a method for diagnosing rheumatoid arthritis. More particularly, this invention relates to a method for objectively diagnosing rheumatoid arthritis by quantitative determination of the presence or absence of rheumatoid arthritis-associated antibodies in patient sera that react with a recombinant antigen. Rheumatoid arthritis is a chronic systemic rheumatic disease that affects a significant percentage of the population. Traditionally, it has been diagnosed subjectively through clinical observation and dominant complaints by a patient. P. Lipsky, Rheumatoid Arthritis, in Harrison's Principles of Internal Medicine 1423 (1987). Thus, clinical diagnosis of rheumatoid arthritis is subject to the skill of the diagnostician and the severity of disease symptoms in the patient. For an objective diagnosis of rheumatoid arthritis, the presence of rheumatoid factor (Rf) in the serum of rheumatoid arthritis patients is routinely determined. Rf has been detected in approximately 70% of patients exhibiting clinical symptoms of rheumatoid arthritis. These patients are thus termed "seropositive." The remaining 30% are classified as having "seronegative" rheumatoid arthritis. Numerous conditions besides rheumatoid arthritis are associated with the presence of rheumatoid factor. Therefore, the presence of Rf does not establish a conclusive diagnosis of rheumatoid arthritis. An objective method of diagnosing rheumatoid arthritis that is more closely correlated with clinical diagnoses than is the presence of Rf in sera is needed. Ideally, such an objective diagnostic test would be quick and easy to perform and would not involve radioisotopes or be invasive to the patient. Web site: http://www.delphion.com/details?pn=US05395753__
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Method for diagnosis of rheumatoid arthritis Inventor(s): Yoshida; Makoto (Kawasaki, JP), Yamanaka; Naoki (Nagoya, JP) Assignee(s): Medecs Co., Ltd. (Aichi, JP), Asahi Medical Co., Ltd (Tokyo, JP) Patent Number: 4,863,850 Date filed: February 16, 1988 Abstract: A substantially pure rheumatoid arthritis specific protein (RASP) and an antibody against the rheumatoid arthritis specific protein (anti-RASP antibody) are disclosed. The RASP is found specifically in the serum or plasma of a patient suffering from rheumatoid arthritis, and may be detected using an anti-RASP antibody easily and effectively. Therefore, the anti-RASP antibody of the present invention is useful for the diagnosis of rheumatoid arthritis by the criterion of the presence of RASP. Excerpt(s): This invention relates to a substantially pure rheumatoid arthritis specific protein. The present invention also relates to an antibody against the rheumatoid arthritis specific protein. More particularly, the present invention is concerned with a protein specifically found in the plasma of a patient suffering from rheumatoid arthritis and an antibody specific for the antigenic determinant of the rheumatoid arthritis specific protein. Conventionally, the diagnosis of rheumatoid arthritis has been effected according to the criteria proposed by the American Rheumatism Association. However, such criteria depend on doctor's observations and dominant complaints by a patient, and therefore, such criteria are insufficient with respect to objectivity and quantitative analysis of the degree of rheumatoid arthritis. For the quantitative analysis of the degree of rheumatoid arthritis, the presence and amount of rheumatoid factor (RF), immune complex (IC) or C-reactive protein (CRP) in the serum or plasma of a patient have been determined. However, such substances are not necessarily specific for the plasma or serum of a patient suffering from rheumatoid arthritis, and therefore, such substances are not useful as a conclusive factor. Web site: http://www.delphion.com/details?pn=US04863850__
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Method for the diagnosis of rheumatoid arthritis Inventor(s): Iwata; Kazushi (Takaoka, JP), Iwata; Hisashi (Nagoya, JP), Kodama; Shuji (Takaoka, JP), Hayakawa; Taro (Nagoya, JP), Kishi; Junichi (Nagoya, JP), Yamashita; Kyoko (Nagoya, JP) Assignee(s): Fuji Yakuhin Kogyo Kabushiki Kaisha (Toyama, JP) Patent Number: 5,190,861 Date filed: April 25, 1989 Abstract: A method for diagnosing rheumatoid arthritis, which is characterized by enzyme-immunologically measuring the amount of collagenase inhibitor present in sera, plasmas or synovial fluids by way of a sandwich assay wherein two different monoclonal antibodies which specifically bind to different antigenic determinants of the collagenase inhibitor are used, and comparing the measured amount with that for normal subjects. Excerpt(s): The present invention relates to a method of the diagnosis of rheumatoid arthritis by way of quantitation of collagenase inhibitor. More particularly the invention relates to a method for carrying out the diagnosis of rheumatoid arthritis, by means of a sandwich enzyme immunoassay for human collagenase inhibitor using monoclonal
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antibodies to bovine collagenase inhibitor (tissue inhibitors of metallproteinases: TIMP), on the basis of the fact that the amount of collagenase inhibitor in sera, plasmas or synovial fluids from patients with rheumatoid arthritis is clearly higher than the amount of collagenase inhibitor in sera, plasmas or synovial fluids, respectively, from normal subjects. The enzyme immunoassay mentioned above is used to mean a method for determining collagenase inhibitor which is characterized in that there are used two different monoclonal antibodies which specifically bind to different antigenic determinants of collagenase inhibitor as an antibody to be bound to a solid phase support and an antibody to be labeled with an enzyme. Among heretofore used methods for the diagnosis of rheumatoid arthritis may be mentioned: Rose's method based on the detection of rheumatoid factor, modified Rose's method by Heller, RAHAtest and RA-test. These methods, however, have such disadvantages that they use complex experimental methods or that it takes many days to go through with the diagnosis. Collagenase inhibitor has been known to exist in human's and other animals' bones, skins, dental pulps, amniotic fluids, bloods and synovial fluids as well as in cultures of joint chondrocytes, synovial cells, fibroblasts derived from varied tissues and fibrosarcomatous cells. As means for determining the amount of collagenase inhibitor methods have heretofore been known which are based on measurement of its biological activity. As described by Eisen et al. in J. Lab. Clin. Med. 75, 258-263 (1973) and also by Cawston et al. in Arthritis and Rheumatism 27, 285-290 (1984), however, it is impossible, with the heretofore known methods of determination, to assay sera, plasmas or synovial fluids for collagenase inhibitor activity since there exist in such fluids proteins, such as.alpha.sub.2 -macroglobulin, which interfere disturbingly with the measurement. Hayakawa, Iwata et al. have already developed a sandwich enzyme immunoassay (EIA) using monoclonal antibodies to bovine collagenase inhibitor, a method which enables specific quantitation of collagenase inhibitor with very small volumes of samples in a precise, straightforward and rapid manner (Japanese Patent Application No. Sho 6242781). The present inventors have discovered that the level of collagenase inhibitor present in human sera, plasmas or synovial fluids apparently increases in association with affliction with rheumatoid arthritis, and found that it is possible to make a diagnosis of rheumatoid arthritis by determining, by the enzyme immunoassay mentioned above, the amount of collagenase inhibitor present in sera, plasmas or synovial fluids. Web site: http://www.delphion.com/details?pn=US05190861__ •
Method for treating rheumatoid arthritis Inventor(s): Farine; Jean-Claude (Eysins, CH), Schulthess; Adrian (Begnins, CH) Assignee(s): Laboratoires OM Societe Anonyme (Geneva, CH) Patent Number: 4,322,405 Date filed: April 6, 1981 Abstract: Lysates derived from strains of Escherichia coli, especially wherein said lysates are derived from at least one of the strainsNCTC 8603, 8621, 8622, 8623, 9026, 9111, 9119, 9707, 9708,I-081, I-082, I-083, I-084, I-085, I-086, I-087, I-088, I-089are useful for treating rheumatoid arthritis. Excerpt(s): is known as an immunobiotherapeutic agent, used against infectious diseases of the urinary and the gastro-intestinal tract (see German OS 30 19 448.0). This latter specification gives full details for the preparation of lysates of these strains. The abovementioned strains NCTC are listed by the National Collection of Type Cultures, London
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(Great Britain), and are accessible to the public, whereas the above-mentioned strains I081 to I-089 have been deposited by the assignee of the present patent application on Mar. 7, 1979, at Collection Nationale de Cultures de Microorganismes, Institut Pasteur, Paris (France). We have now surprisingly found that bacterial lysates of Escherichia coli, and especially bacterial lysates of the above-mentioned strains NCTC and I, produce an anti-inflammatory action in animals. They have a non-specific immunostimulatory action in humans and are useful in patients with rheumatoid arthritis (RA). RA is known as an inflammatory disease with immunological etiology. In the following animal model, lysates of Escherichia coli showed an action in the chronic inflammatory phase. Web site: http://www.delphion.com/details?pn=US04322405__ •
Method for treatment of non-rheumatoid arthritis Inventor(s): Macias; William Louis (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 6,610,728 Date filed: February 24, 2000 Abstract: A method is disclosed for the treatment of non-rheumatoid arthritis by administering to a mammal in need thereof a therapeutically effective amount of an sPLA.sub.2 inhibitor. Excerpt(s): The present invention is directed to a method for treating non-rheumatoid arthritis. More specifically, the present invention is directed to a method for treating the causes and/or the symptoms of various forms of non-rheumatoid arthritis in mammals by administering a therapeutically effective amount of an sPLA.sub.2 inhibitor. The most common form of non-rheumatoid arthritis is osteoarthritis, a degenerative joint disease which primarily affects cartilage that covers and cushions the ends of the bones causing it to fray, wear, ulcerate, and in extreme cases, to disappear entirely leaving a bone on bone joint. The disease can result in severe disability particularly in the weight bearing joints such as the knees, hips, and spine. Osteoarthritis is distinguishable, for example, from rheumatoid arthritis in that osteoarthritis involves little or no inflammation and is confined to the joints and surrounding tissue where there is a breakdown or disintegration of cartilage and other tissue thereby making it difficult for the joints to operate properly. The occurrence of osteoarthritis frequently increases with advancing years. Non-rheumatoid arthritis is often treated with acetaminophen and ibuprofen. In addition, non-steroidal anti-inflammatory drugs (NSAIDSs) may be used to relieve pain by blocking the production of prostaglandins (e.g., choline magnesium salicylate, salicylsalicyclic acid). Corticosteroids such as methylprednisone, prednisone, and cortisone may be used to relieve pain and swelling. Each of these known drug therapies has possible long-term disadvanges such as kidney or liver damage, heartburn, stomach upset, ulcers, gastrointestinal bleeding, mood swings, weight fain, high blood pressure, muscle weakness and lowered resistance to infection. Web site: http://www.delphion.com/details?pn=US06610728__
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Method for treatment of rheumatoid arthritis Inventor(s): Jones; Frank R. (Edmonds, WA), Snyder, Jr. Harry W. (Seattle, WA), Balint, Jr. Joseph P. (Seattle, WA) Assignee(s): Cypress Bioscience, Inc. (San Diego, CA) Patent Number: 5,782,792 Date filed: December 12, 1994 Abstract: Rheumatoid arthritis is treated by the extra corporeal removal of IgG and IgGcontaining circulating immune complexes from the patient's blood. Removal is preferably accomplished by exposing the blood or blood plasma to a protein A immunoadsorbent which binds to IgG-containing immune complexes with high affinity. Excerpt(s): The present invention relates generally to the treatment of autoimmune disorders by extracorporeal plasma perfusion to remove immunoglobulin and immune complexes. More particularly, the present invention relates to the treatment of rheumatoid arthritis (RA) by continuous or discontinuous plasma perfusion through an immunoadsorbent capable of binding immunoglobulins and immune complexes. Autoimmune disorders are characterized by the destruction of a patient's body tissues by the patient's own immune system. Severe harm can arise from such a misdirected immune response, causing illness and even death to the patient. Rheumatoid arthritis is an autoimmune disorder of unknown etiology which is characterized by the presence of auto-antibodies. Rheumatoid arthritis (RA) is a chronic disease which can exhibit a variety of systemic manifestations. This disease has an unknown etiology and characteristically exhibits a persistent inflammatory synovitis which usually involves peripheral joints in a symmetric distribution. Despite the destructive potential of RA, its course can be quite variable. In about two-thirds of patients, a chronic polyarthritis begins insidiously with fatigue, anorexia, generalized weakness and vague musculoskeletal symptoms until the appearance of synovitis becomes apparent. In about 10% of patients, the onset can be more acute with rapid development of polyarthritis. In about one-third of patients, symptoms may initially be confined to one or a few joints. Overall, most patients will experience an intermediate course of the disease. As described above, the potential of the inflammation to cause cartilage destruction, bone erosions and, ultimately, joint deformities is the most important feature of this disease. Web site: http://www.delphion.com/details?pn=US05782792__
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Method of treating arthritis, including rheumatoid arthritis, with 166 Holmium radionuclide Inventor(s): Lieberman; Ephraim (Suffern, NY), Thornton; Alfred K. (New Hampton, NY), Bordoni; Maurice E. (Westtown, NY) Assignee(s): Cadema Medical Products, Inc. (Middletown, NY) Patent Number: 5,026,538 Date filed: June 16, 1989 Abstract:.sup.166 Holmium in a carrier metallic hydroxide aggregate is disclosed for the treatment of arthritis and, in particular, rheumatoid arthritis. The compound disclosed preferably has a particle size of 1 to 40 microns, Beta energy emissions in the range of 1.76-1.84 MeV, low levels of gamma ray emissions and a radioactive half-life of 26.8
Patents 381
hours. The preferred metallic hydroxide is selected from the group consisting of Ferric Hydroxide, Aluminum Hydroxide, Bismuth Hydroxide, Chromium Hydroxide, Cupric Hydroxide, Manganese Hydroxide and Stannous Hydroxide. Methods are also disclosed for the preparation of the compound, as well as for the methods of its administration to a patient in need thereof. Excerpt(s): The present invention relates to radioactive compounds, methods for the preparation thereof and a method for the treatment of arthritis, including rheumatoid arthritis. Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately six million of all arthritis sufferers are afflicted rheumatoid arthritis. Of these, over fifty percent (50%) ultimately will have involvement of the knee joint, over eighty percent (80%) will involve the hand joint and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow and shoulder. Rheumatoid arthritis is believed to be an autoimmune disease wherein parts of the body are attacked by antibodies manufactured in the body. These antibodies may be produced in response to viruses present in the body. While the mechanism for rheumatoid arthritis is not defined, it is a systemic disease. When the disease is active, the erythrocyte sedimentation rate (ESR) is elevated and the blood tests positive for rheumatoid factor. Web site: http://www.delphion.com/details?pn=US05026538__ •
Method of treating rheumatoid arthritis Inventor(s): Wechter; William J. (Kalamazoo, MI), Brooks; Carter D. (Texas Township, Kalamazoo County, MI) Assignee(s): The Upjohn Company (Kalamazoo, MI) Patent Number: 4,118,484 Date filed: March 29, 1976 Abstract: A process of treatment for the management of the condition known as rheumatoid arthritis. The process manages rheumatoid arthritis by controlling the inflammatory process in a rheumatoid joint by the intra-articular administration to said joint of an effective amount for controlling the inflammatory process of certain N.sup.4 acyl-ara-cytidines, 5'-O-acyl-ara-cytidines and pharmaceutically acceptable acid addition salts thereof, and pharmaceutically acceptable acid addition salts of 5'-O-acyl2,2'-anhydro-ara-cytidines. Excerpt(s): The invention concerns a method of treating rheumatoid arthritis in mammals including humans. More specifically, the invention concerns a method of controlling the inflammatory process in a rheumatoid joint of a mammal. Belgium Pat. No. 773,027 of Mar. 24, 1972, and U.S. Pat. No. 3,920,630 issued Nov. 18, 1975, disclose 2,2'-anhydro-ara-cytidine compounds as useful in the treatment of autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. Belgium Pat. No. 773,027 and U.S. Pat. No. 3,920,630 do not disclose which, if any, of the compounds are effective as an intra-articularly administered agent in controlling the inflammatory process in a rheumatoid joint. Web site: http://www.delphion.com/details?pn=US04118484__
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Method of treating rheumatoid arthritis Inventor(s): Meier; Albert H. (Andover, MA), Cincotta; Anthony H. (Andover, MA) Assignee(s): Ergo Science Incorporated (Charlestown, MA) Patent Number: 5,905,083 Date filed: June 2, 1995 Abstract: Disclosed are methods for rectifying or ameliorating abnormal responses of mammalian immune systems, such as rheumatoid arthritis. Also disclosed are methods for modifying normal responses of the mammalian immune system. Further disclosed are methods for accomplishing the foregoing by administering to a mammal a prolactin reducer and/or enhancer at a pre-determined time or times during a 24-hour period that results in modification of the mammal's abnormal prolactin profile so that it approaches or conforms to the prolactin profile of a young, healthy mammal of the same species (or to a standard profile generated from such individuals). Additionally, methods of upregulating or augmenting an immune response in a mammal are disclosed. Excerpt(s): This invention relates to methods for rectifying or ameliorating abnormal responses of the mammalian immune system, and modifying normal responses of the mammalian immune system. More particularly, this invention relates to methods employing the alteration of prolactin rhythms as a method of adjusting mammalian immune response. The importance of neuroendocrine regulation of immunity has become increasingly evident during the past decade (Besedovsky, H. O. et al., J. Immunol. 135:750s-754s, 1985; Blalock, J. E., Physiol. Rev. 69: 1-54, 1989; Berozi, I., Dev. Comp. Immunol. 13:329-341, 1989). Much of this interest has focused on the anterior pituitary hormone prolactin, which has been reported to have potent, albeit inconsistent and often conflicting, effects on immune activity (Gala, R. R., Proc. Soc. Exp. Biol. Med. 198:5-13, 1991; Nicoletti, J. et al., Reprod. Immunol. 15:113-121, 1989; Vidaller, A., et al., Clin. Immunol. Immunopathol. 38:337-343, 1986; Gerli, R. et al., Clin. Immunol. 7:463470, 1987). The role of prolactin in immunity is exemplified by studies demonstrating exogenous prolactin-induced restoration of immune competence in hypophysectomized mammals (Gala, R. R., Proc. Soc. Exp. Biol. Med. 198:5-13, 1991; Bercal, I. et al., Acta Endocrinol. 98:506-513, 1981). In intact animals, prolactin administration has been associated with numerous immunological effects including stimulation of cellular or antibody responses, as well as stimulation of various immune system upregulating substances such as IL-2 (both IL-2 production and IL-2 receptor expression); enhancement of lymphocyte number, activity and mitogenic responses; and augmentation of macrophage cytotoxicity (Gala, R. R., Proc. Soc. Exp. Biol. Med. 198:513, 1991; Bernton, E. W. et al., Science 239:401-404, 1988; Rovensky, J. et al., Int. J. Immuno. Pharmac. 13:267, 1991). Web site: http://www.delphion.com/details?pn=US05905083__
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Method of treating rheumatoid arthritis and osteoarthrosis using tetrahydro WS9326A Inventor(s): Fujii; Takashi (Ikeda, JP), Tomoi; Masaaki (Higashiosaka, JP) Assignee(s): Fujisawa Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 5,616,556 Date filed: November 18, 1993
Patents 383
Abstract: Rheumatoid arthritis and osteoarthrosis are treated by administering an effective amount of tetrahydro-WS9326A to a human being or animal suffering from rheumatoid arthritis or osteoarthrosis. Excerpt(s): This invention relates to an antiinflammatory or gastrointestinal motilitymodulating composition comprising a peptide derivative of the general formula (I) presented hereafter or a pharmaceutically acceptable salt thereof as an active ingredient, which composition finds application in the field of medicine. The peptide derivative of the invention, represented by the general formula (I) given below, is a per se known compound and is known to possess pharmacological activities such as substance P antagonism and neurokinin A antagonism (e.g. EP 0336230A2). However, there has not been the awareness that this peptide derivative has antiinflammatory or gastrointestinal motility-modulating activity. is a single bond or a double bond, or a pharmaceutically acceptable salt thereof as an active ingredient. Web site: http://www.delphion.com/details?pn=US05616556__ •
Method of treating rheumatoid arthritis using tetracycline Inventor(s): Cabezas; Orestes (10201 Fontainebleau Blvd., Unit 205, Miami, FL 33172) Assignee(s): none reported Patent Number: 5,250,442 Date filed: April 8, 1993 Abstract: A method of treating rheumatoid arthritis which includes first, taking a blood test to determine a rate of erythrocyte sedimentation and a rheumatoid factor, and then fasting for a 12-hour period prior to orally administering a 500 milligram dosage of tetracycline achromycin, and observing any change in the symptoms of the rheumatoid arthritis including reduction of swelling and pain in the affected sites. This process is repeated over 24-hour cycles until the rheumatoid factor has decreased by at least 50% from the first determined level prior to treatment and erythrocyte sedimentation decreased, at which point the 24-hour cycles are continued, reducing the dosage of tetracycline achromycin to 250 milligrams until the symptoms of the rheumatoid arthritis condition disappear. Excerpt(s): The present invention relates to a method for treating rheumatoid arthritis to alleviate the symptoms thereof. Presently, an estimated 7,000,000 Americans suffer from rheumatoid arthritis. The symptoms of rheumatoid arthritis including pain and swelling of the smaller joints in the hands and feet. The affected joints become swollen, painful and warm to the touch during the initial attack and ensuing flare-ups. Often, the joints in the hands and the feet will ache or become stiff after extended periods of motionless such as after sleeping. Rheumatoid arthritis is believed to be an autoimmune disease in which the body's immune system literally attacks itself. It is believed that rheumatoid arthritis initially develops from a virus which upsets the immune system. In response, the body's disease fighting cells attack the joints causing inflammation. Web site: http://www.delphion.com/details?pn=US05250442__
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Method of treatment of rheumatoid arthritis Inventor(s): Scheinberg; Israel H. (5447 Palisades Ave., Bronx, NY 10471) Assignee(s): none reported Patent Number: 4,487,780 Date filed: February 5, 1982 Abstract: Rheumatoid arthritis is treated with substituted cysteine compounds having a lower toxicity-to-effectiveness ratio than penicillamine. Such compounds are specific alpha-substituted cysteines, beta-monosubstituted cysteines, beta-di-substituted cysteines other than penicillamine, N-acetyl penicillamine and the N-acetyl derivatives of the alpha and beta-substituted compounds mentioned above.Any of the compounds may be used synergistically in combination with suitable copper compounds or with suitable gold compounds in the treatment of arthritis.The same compounds are effective in the treatment of cystinuria and heavy metal poisoning. The same compounds as well as penicillamine are effective in combination with copper in the treatment of heavy metal poisoning. Excerpt(s): Rheumatoid arthritis, commonly referred to as RA, is the second most crippling disease in man, ranking immediately behind cardiovascular defects. Until recently no effective treatment for RA has been known. A number of drugs which are moderately effective in the treatment of this disease have been found, examples being Dpenicillamine which is.beta.,.beta.-dimethylcysteine and certain compounds of gold, such as gold sodium thiomalate, aurothioglucose and sources of auric or aurous ion. Of these compounds, the most promising is the recently discovered penicillamine, a natural metabolite of penicillin. Unfortunately, not all patients respond to this medication; also, it carries with it considerable toxicity so that it can, in fact, be lethal. Another difficulty is that penicillamine is slow-acting so that generally it requires 8 to 12 weeks before it can be determined whether the patient is responding and whether the dosage needs adjusting. D-penicillamine usually produces a decrease in the titer of rheumatoid factor, an index of its specific therapeutic efficacy for this human disease. There are no genuine animal models of rheumatoid arthritis. At the present time, most rheumatologists treat moderately severe RA that has not responded to salicylates with either a gold compound or D-penicillamine. Penicillamine is also used initially in some patients with severe RA, and those in whom rheumatoid lung disease, vasculitis, amyloidosis, Felty's syndrome or rheumatoid nodulosis complicate the clinical picture. Web site: http://www.delphion.com/details?pn=US04487780__
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Methods and compositions for treating rheumatoid arthritis Inventor(s): Barlozzari; Teresa (Wellesley, MA), Haupt; Andreas (Northborough, MA), Banerjee; Subhashis (Shrewsbury, MA) Assignee(s): BASF Aktiengesellschaft (Ludwigshafen, DE) Patent Number: 6,015,790 Date filed: October 6, 1997 Abstract: The present invention provides compositions and methods for the treatment of rheumatoid arthritis in a subject wherein one or more compounds of Formula I as defined herein alone or in combination with one or more other antiarthritic drugs provide suppression of rheumatoid arthritis.
Patents 385
Excerpt(s): Rheumatoid arthritis is generally considered an autoimmune disease that is thought to be associated with activity of autoreactive T cells (See, e.g., Harris, E. D., Jr., The New England Journal of Medicine, 322: 1277-1289 (1990)). Despite advances in treatment, rheumatoid arthritis remains a serious health problem. Although rarely fatal, arthritis is a major cause of morbidity, loss of time from work, lost productivity and decrease in quality of life. Rheumatoid arthritis causes severe pain and loss of joint mobility and can make accomplishing even simple tasks difficult. Current treatment methods and regimes for rheumatoid arthritis include administration of non-steroidal anti-inflammatory drugs such as acetylsalicylic acid (aspirin), ibuprofen, naproxen and other such agents, gold compounds, penicillamine, methotrexate, cytotoxic agents (e.g., azothrioprine), 4-aminoquinoline agents, and immunomodulators. However, improved treatments of rheumatoid arthritis, which can suppress or ameliorate symptoms such as inflammation, swelling, abnormal neovascularization, bone erosion, or cartilage erosion are needed. Preferably, such an improved method of treatment should be able to be combined with other treatment methods, should work rapidly to cause regression or stabilization of symptoms, and should be well tolerated. Preferably, such a treatment regime should also be useful in prophylaxis in susceptible individuals. --CH(CH.sub.3) CH(CH.sub.3).sub.2, also referred to as 1,2-dimethylpropyl. Web site: http://www.delphion.com/details?pn=US06015790__ •
Methods and materials for evaluating rheumatoid arthritis Inventor(s): Weyand; Cornelia M. (Rochester, MN), Goronzy; Jorg J. (Rochester, MN) Assignee(s): Mayo Foundation for Medical Education and Research (Rochester, MN) Patent Number: 6,555,320 Date filed: September 1, 1999 Abstract: The invention provides methods and materials for diagnosing a rheumatoid arthritis condition in a patient. Specifically, the invention provides methods and materials for classifying a rheumatoid arthritis condition as diffuse, follicular, or granulomatous. In addition, the invention provides methods and materials for determining if an individual suffering from a rheumatoid arthritis condition will develop severe disease. Excerpt(s): The invention relates to methods and materials for evaluating rheumatoid arthritis as well as for determining an individual's predisposition to have severe rheumatoid arthritis disease. Rheumatoid arthritis (RA) affects individuals in the prime of their life and is feared because of its potential to cause chronic pain and irreversible damage of tendons, ligaments, joints, and bones. The symmetrical involvement of small peripheral joints has an enormous impact on hand and foot functions and poses therapeutic challenges that cannot be easily overcome by joint replacement. Also, systemic manifestations of RA are not rare and can range from relatively minor problems, such as rheumatoid nodules, to life-threatening organ disease. In addition, RA is a systemic inflammatory disease that primarily manifests itself as synovial inflammation of diarthrodial joints. The typical histopathological changes include dense infiltration of the synovial membrane by mononuclear cells, neoangiogenesis, and hypertrophy and hyperplasia of the synovial lining (Harris E D (ed); Rheumatoid Arthritis, Philadelphia, WB Saunders Co., pp.3-212 (1997); and Hale L P, Haynes B F: Pathology of rheumatoid arthritis and associated disorders. Arthritis and Allied Conditions. A textbook of Rheumatology. Edited by Koopman W J. Baltimore, Williams & Wilkins, pp.993-1016 (1997)). The etiopathogenesis of the syndrome is not understood.
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Several lines of evidence support a central role of T lymphocytes in the disease-specific pathogenic events (Todd, et al. Science, 240:1003-1009 (1988); Panayi, et al., Arthritis Rheum, 35:729-735 (1992); and Goronzy J J, Weyand C M: Rheum Dis Clin North Am, 21:655-674 (1995)). An alternative hypothesis, namely, that macrophages are the pivotal cell type in rheumatoid synovitis, has also been proposed (Firestein G S, Zvaifler N J: Arthritis Rheum 33:768-773 (1990); and Burmester, et al., Arthritis Rheum, 40:5-18 (1997)). Whether only T cells or only macrophages or both are the causative elements in RA remains a matter of controversy (Feldmann, et al., Cell, 85:307-310 (1996); and Fox, Arthritis Rheum 40:598-609 (1997)). Web site: http://www.delphion.com/details?pn=US06555320__ •
Methods and materials for treatment of rheumatoid arthritis Inventor(s): McMichael; John (P.O. Box 81, Cambridge Springs, PA 16403) Assignee(s): none reported Patent Number: 4,704,273 Date filed: February 27, 1986 Abstract: Disclosed are methods and compositions useful for alleviating the symptoms of rheumatoid arthritis. In preferred embodiments, the compositions are administered in essentially minute "neutralizing" doses. The compositions comprise mixtures of histamine, immunoglobulin G provocative of RF formation or an immunologically active fraction thereof, collagen and either attenuated measles virus or immunologically active fraction thereof. Illustratively significant relief of symptoms of arthritis disease symptoms is achieved through parenteral (e.g., subcutaneous or sublingual) administration of such compositions. Excerpt(s): This application is a continuation-in-part of my copending U.S. application Ser. No. 708,274 filed March 5, 1985 which is a division of my U.S. application Ser. No. 378,752 filed May 17, 1982, now U.S. Pat. No. 4,521,405. The present invention relates generally to the treatment of disease states involving immunological factors and more particularly to methods and materials for alleviation of symptoms of nonanaphylactic disorders wherein disease pathology results in whole or part from the victim's own humoral and/or cell-medicated immune response to one or more immunogenic substances. Disease states involving immunological factors may be seen to broadly comprise (1) immunodeficiency diseases, and (2) disorders wherein tissue injury occurs as a result of a humoral or cell-mediated response to immunogens (e.g., antigens) of endogenous or exogenous origin. This latter group of immunological disorders is frequently referred to as involving immune "hypersensitivity", with the numerous disease states comprehended by the term classified according to four hypersensitivity "reaction" types. Web site: http://www.delphion.com/details?pn=US04704273__
Patents 387
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Methods of treating rheumatoid arthritis using chimeric anti-TNF antibodies Inventor(s): Vilcek; Jan (New York, NY), Le; Junming (Jackson Heights, NY), Daddona; Peter (Menlo Park, CA), Siegel; Scott (Westborough, MA), Ghrayeb; John (Thorndale, PA), Knight; David (Berwyn, PA) Assignee(s): Centocor, Inc. (Malvern, PA), New York University Medical Center (New York, NY) Patent Number: 5,698,195 Date filed: October 18, 1994 Abstract: Anti-TNF antibodies, fragments and regions thereof which are specific for human tumor necrosis factor-.alpha. (TNF.alpha.) and are useful in vivo for diagnosis and therapy of a number of TNF.alpha.-mediated pathologies and conditions, including rheumatoid arthritis as well as polynucleotides coding for murine and chimeric antibodies, methods of producing the antibody, methods of use of the anti-TNF antibody, or fragment, region or derivative thereof, in immunoassays and immunotherapeutic approaches are provided. Excerpt(s): The present invention in the field of immunology and medicine relates to anti-tumor necrosis factor (TNF) antibodies, anti-TNF peptides and nucleic acids encoding therefor, and to pharmaceutical and diagnostic compositions and production, diagnostic and therapeutic methods thereof, and to methods for treating human TNFmediated pathologies. Cells other than monocytes or macrophages also make TNF.alpha. For example, human non-monocytic tumor cell lines produce TNF (Rubin, et al., J. Exp. Med. 164:1350 (1986); Spriggs, et al., Proc. Natl. Acad. Sci. USA 84:6563 (1987)). CD4.sup.+ and CD8.sup.+ peripheral blood T lymphocytes and some cultured T and B cell lines (Cuturi, et al., J. Exp. Med. 165:1581 (1987); Sung, et al., J. Exp. Med. 168:1539 (1988)) also produce TNF.alpha. Recent evidence associates TNF with infections (Cerami, et al., Immunol. Today 9:28 (1988)), immune disorders, neoplastic pathologies (Oliff, et al., Cell 50:555 (1987)), autoimmune pathologies and graft-versus host pathologies (Piguet, et al., J. Exp. Med. 166:1280 (1987)). The association of TNF with cancer and infectious pathologies is often related to the host's catabolic state. Cancer patients suffer from weight loss, usually associated with anorexia. Web site: http://www.delphion.com/details?pn=US05698195__
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Mouse model for rheumatoid arthritis Inventor(s): Hayashi; Takuma (Malden, MA), Faustman; Denise L. (Weston, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,414,218 Date filed: January 18, 2000 Abstract: Nonobese Diabetic Mice (NOD mice) that do not develop diabetes may be bred to produce F.sub.1 offspring that develop a condition that closely mimics rheumatoid arthritis (RA) in humans. The RA-like disease in the F.sub.1 mice, designated NOD-RA mice, is similar to human RA in clinical, radiological, histological and serological characteristics. The parents (F.sub.0) and their progeny (F.sub.1) are not diabetic and never develop hyperglycemia, and the parental mice (F.sub.0) do not themselves exhibit any symptoms of the RA-like condition that afflicts some of their progeny. The incidence, penetrance, gender domination, progression, and lifelong
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exacerbation of symptoms after pregnancy shown in the RA-like condition afflicting NOD-RA mice are all comparable to phenomena observed in the human disease. The NOD-RA mice provide a new spontaneous model of human RA that will be useful for studying rheumatoid arthritis and testing new drugs and reagents for treating or diagnosing the disease. Excerpt(s): The present invention pertains to the field of medical research, particularly to the development of mammalian models of human rheumatoid arthritis. Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint swelling, deformation and, ultimately, destruction, culminating in severe physical disability. De Graaf et al., in The Epidemiology of Chronic Rheumatism, Dellgren and Ball, eds. (Blackwell, Oxford, 1963), pp. 446-56; Meenam et al., Arthritis Rheum., 24:544-50 (1981); Gabriel et al., J. Rheumatol., 26:1269-74 (1999); James, Clin. Exp. Rheumatol., 17:392-93 (1999). RA is a progressive condition with well-recognized symptoms including symmetrical peripheral joint swelling and synovial inflammation while sparing the axial skeleton; the presence of rheumatoid factor (RF) autoantibodies; increased concentrations of interleukin-6 (IL-6) in serum and synovial fluid; and pregnancyinduced disease remission followed by severe postpartum flares, that is, while women with RA commonly undergo remission during pregnancy, the disease returns and may be even more severe and show a new onset or more accelerated course after delivery. See, Turgen, in Immunology and Serology in Laboratory Medicine, 2.sup.nd edition, Shanahan, ed. (Mosby Year Book, St. Louis, 1996), pp. 387-98; Hirano et al., Eur. J. Immunol., 18:1797-1801 (1988); Wilder et al., Ann. N.Y. Acad. Sci., 876:14-31 (1999); Iijima et al., J. Rheumatol., 26:755-56 (1999); Ostensen, Ann. N.Y. Acad. Sci., 876:131-43 (1999). In medical research directed to understanding, diagnosing and treating RA, several animal models of the disease have been described, but no spontaneous animal model that closely mimics all the features of the human disease has been discovered. Thus, it would greatly advance discovery research in the field of RA research if a mammalian model faithfully exhibiting the same characteristic physical symptoms of RA could be obtained. Web site: http://www.delphion.com/details?pn=US06414218__ •
Photodynamic therapy for the destruction of the synovium in the treatment of rheumatoid arthritis and the inflammatory arthritides Inventor(s): Trauner; Kenneth (Sacramento, CA), Hasan; Tayyaba (Arlington, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 5,368,841 Date filed: February 11, 1993 Abstract: A method of treating proliferative diseases of the synovial joint using photodynamic therapy. In particular the method of the invention may be used to destroy synovial tissue in inflammatory joint conditions associated with diseases such as rheumatoid arthritis, lupus erythematosus and other rheumatoid variants. A number of methods of delivery are provided, some of which are non invasive. Excerpt(s): The invention relates to the use of photodynamic therapy for the destruction of diseased synovium. Photodynamic therapy generally refers to an experimental cancer treatment modality that selectively kills cancer cells by an interaction between absorbed light an a retained photoactivatable agent (Kessel, Photochem. Photobiol. 44:489-493; Bottiroli et al., Photochem. Photobiol. 47:209-214, 1988; Salet et al., Photochem.
Patents 389
Photobiol. 53:391-3, 1991; Gross, Photobiological Techniques (chapter 9), Valenzeno et al. eds., Plenum Press, New York, 1991; Star et al., Photochem and Photobiol, B: Biology 1:149-167, 1987; and Jori et al., Photodynamic Therapy of Neoplastic Disease, Kessel ed., CRC Press, Boca Raton, Fla., 1989). Chemical sensitization of live tissues by light was first reported in 1900 by Raab. Uptake of hematoporphyrin derivative (HPD) in neoplastic tissue was first described by Auler and Banzer (Z. Krebforsch 53:65-68, 1942). Uptake was later confirmed by fluorescence by Figge et al (Proc. Soc. Exp. Biol. Med. 68:640-641, 1948). Lipson et al. demonstrated tumor localization of HPD in 1960 (JNCI 26:1-12, 1961). The HPD semipurified mixture of porphyrins was later further purified to a combination of esters and ethers of dihematoporphyrin (DHE). The formulation predominantly in use is marketed as Photofrin.RTM. and HPD/Photofrin.RTM. was the first FDA approved photosensitizing agent available for PDT trials. Photofrin.RTM. has subsequently been tested extensively for the destruction of multiple tumors in numerous medical disciplines (Dougherty et al., In Photodynamic Therapy of Neoplastic Disease, Kessel ed., CRC Press, Boca Raton, Fla., 1989). Web site: http://www.delphion.com/details?pn=US05368841__ •
Polynucleotides encoding MIP-1.alpha., MCP-1, MIP-1.beta., Rantes and TNF-.alpha., and methods for treating rheumatoid arthritis Inventor(s): Karin; Nathan (Haifa, IL) Assignee(s): Rappaport Family Institute for Research in the Medical Sciences (Haifa, IL) Patent Number: 6,420,346 Date filed: February 7, 2000 Abstract: A method of treating rheumatoid arthritis of an individual is disclosed. The method comprises the step of expressing within the individual at least an immunologically recognizable portion of a cytokine from an exogenous polynucleotide encoding the at least a portion of the cytokine, wherein a level of expression of the at least a portion of the cytokine is sufficient to induce the formation of anti-cytokine immunoglobulins which serve for neutralizing or ameliorating the activity of a respective and/or cross reactive endogenous cytokine, to thereby treat rheumatoid arthritis. Excerpt(s): The present invention relates to pharmaceutical compositions and methods for treating rheumatoid arthritis in an individual. More particularly, the present invention relates to DNA vaccination approaches which induce the breakdown of selftolerance to cytokines and as such inhibit the progression of the disease. Rheumatoid arthritis (RA) is an inflammatory disorder characterized by infiltration of leukocytes into the synovial tissue (ST) and synovial fluid (SF) of joints (Harris, 1990). Depending on the type of immunization, a single administration of complete Freund's adjuvant (CFA) may result in the development of a local inflammatory process or chronic poly adjuvant induced arthritis (AIA, also termed AA) which histologically and clinically resembles human RA (Holoshitz et al., 1983). In the scientific and medical communities, AIA is considered a reliable animal model for testing drugs and treatments for RA. In both diseases proinflammatory cytokines and chemokines are believed to play a pivotal role in the attraction of leukocytes to the site of inflammation and in the initiation and progression of the inflammatory process. The role of proinflammatory cytokines, particularly TNF-.alpha. and IL-1, in disease manifestation has been intensively studied and explored in experimental models that have been expanded to clinical trials (Arend and Dayer, 1995; Arend et al., 1994; Elliott et al., 1994; Feldmann et al., 1997; Moreland et
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al., 1997; Moreland et al., 1996; for a general review, see also, Feldmann et al., 1996). Other cytokines such as IL-4, TGF-.beta., IL-8, IL-17, IL-10, IL-11, IL-12 and IL-15 have also been implicated in the regulation of the disease. Such regulation can be attributed to either their direct effect on disease manifestation, their synergistic effect with other proinflammatory cytokines/chemokines, or their involvement in the regulation of chemokine transcription, and production (Badolato and Oppenheim, 1996; Badolato et al., 1997; Butler et al., 1999; Chabaud et al., 1998; Evans et al., 1998; Feldmann et al., 1996; Kasama et al., 1999; Ma et al., 1998; Parks et al., 1998; Sato et al., 1996; Schimmer et al., 1998; Schrier et al., 1998; Wahl et al., 1993). Web site: http://www.delphion.com/details?pn=US06420346__ •
Polyvalent equine immune serum composition and method for treating rheumatoid arthritis Inventor(s): Stephan; Peter M. (London, GB2) Assignee(s): Peter Stephan Center, Ltd. (Miami, FL) Patent Number: 4,732,752 Date filed: October 23, 1986 Abstract: A composition and method for treating rheumatoid arthritis, osteoarthritis, and related diseases which comprises administering an effective amount of an equine immune serum, in dosage form, to a patient. The equine immune serum is obtained from horses which have been immunized with a solution containing tissue from prenatal or pregnant pigs. Excerpt(s): The present invention relates to a composition and method for treating rheumatoid arthritis, osteoarthritis, non-specific rheumatism and other related diseases in humans. Arthritis is a term generally used to describe a condition of inflammed joints which is characterized by pain and swelling. Both osteoarthritis and rheumatoid arthritis may result in stiffness, swelling and a considerable amount of pain. Treatment generally includes rest, the application of heat, and the administration of antiinflammatory drugs. Often, the treatment further includes the administration of diseasemodifying anti-rheumatic drugs such as gold, methotrexate and penicillamine. However, since these drugs are quite toxic and often result in serious side-effects, they must be used with caution. In view of the severity of rheumatoid arthritis, osteoarthritis, and other related diseases, there is a great need for a drug which is easily tolerated and free from serious side-effects. Thus, it is an object of the present invention to provide a novel composition for the treatment of rheumatoid arthritis, osteoarthritis, and related diseases. Web site: http://www.delphion.com/details?pn=US04732752__
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Prevention and treatment of rheumatoid arthritis Inventor(s): Stolle; Ralph J. (Lebanon, OH), Beck; Lee R. (Birmingham, AL) Assignee(s): Stolle Research and Development Corporation (Cincinnati, OH) Patent Number: 4,732,757 Date filed: December 9, 1983
Patents 391
Abstract: There is disclosed a novel method and product for the treatment and prevention of rheumatoid arthritis. The method involves passive immunization against a mixed spectrum of infectious bacteria which reside in the human gastrointestinal tract. The passive immunization is accomplished by oral injestion of IgG immunoglobulin obtained from the milk of cows that have been immunized against a specific spectrum of bacterial types. A unique combination of bacterial species is formulated into a vaccine which is used to immunize dairy cattle. The IgG antibody obtained from the milk of the immunized cows constitutes the product of the invention. Excerpt(s): This application is related to an application in the name of Lee Randolph Beck, Ser. No. 776,249 filed March 10, 1977. A number of years ago it was commonly believed that rheumatoid arthritis had an infectious etiology. This view is not popular today, although the inflammatory features and constitutional manifestations of rheumatoid arthritis--the synovitis and granulomatous lesions, the fever, tachycardia, leukocytosis, lymphadenopathy and occasional spelnomegaly, the accelerated erythrocyte sedimentation rate and other changes in "acute phases reactants"--are all compatible with an infectious process. Competent and repeated bacteriologic studies have failed to recover consistently a single infectious agent from the blood, synovial fluid, synovial tissues or subcutaneous nodules. Attempts to transmit the disease by injecting joint fluid from patients with rheumatoid arthritis into the joints of other human subjects have been unsuccessful. Subcutaneous nodules have failed to survive following homologous transplantation (Bauer, et al, 1951) the Practitioner 166:5. An infectious process may appear to precipitate the onset of rheumatoid arthritis in a significant number of patients, and may exert a deleterious influence on the course of the disease when it has already been established. There is statistical evidence to support this clinical impression (Lewis-Faning, 1950) Ann Rheum. Dis., Suppl. 9. Web site: http://www.delphion.com/details?pn=US04732757__ •
Process and product for treatment of rheumatoid arthritis Inventor(s): Moore; Eugene R. (5600 Woodview Pass, Midland, MI 48642) Assignee(s): none reported Patent Number: 5,529,786 Date filed: February 28, 1994 Abstract: This invention provides a therapeutic pill comprising animal tissue containing a therapeutic amount of Type II collagen and a method of preparing animal tissue containing Type II collagen for treatment of Rheumatoid Arthritis in humans. Excerpt(s): Rheumatoid Arthritis is a painful and often crippling disease that initially results in swollen and imflammed joints, but often progresses to deformed or completely destroyed joints. This is a result of the body mistakenly attacking collagen, which is the major portion of cartilage tissue. Cartilage tissue serves the function of a lubricant in the joints, keeping bone from rubbing on bone. As the disease progresses and more of the cartilage is destroyed, bone does begin to wear on bone. This results in even more severe pain and ultimately destruction of the joint itself. As the disease progresses, the body sometimes attacks other collagen in the soft tissues of the body which can cause a variety of arthritis-related diseases. In order to initiate the disease, it is apparent that an individual must have an inherent (perhaps genetic) susceptibility. Given this susceptibility, there is now strong evidence that the disease is initiated by exposure to the Epstein-Barr virus. The ability of the Epstein-Barr virus to initiate
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Rheumatoid Arthritis has been linked to a key amino acid sequence which is identical to a sequence found in human collagen. Thus, in generating antibodies to destroy the Epstein-Barr virus, the body generates antibodies that are also capable of attacking its own collagen. In a similar manner, arthritis has been initiated in rats by the intradermal injection of highly purified Type II collagen extracted from chicken cartilage or by the well known complete Freund Adjuvant. It was also shown that rats could be prevented from getting arthritis or the effects greatly reduced from this injection of highly purified collagen. This was accomplished by feeding the same highly purified collagen to the rats for several days prior to the injection. It was also shown with rats that, once arthritis had been induced, the effects of the disease could be reduced by the oral administration of the same highly purified collagen. In a later study with humans having severe arthritis it has been shown that the oral administration of the highly purified collagen is similarly beneficial to humans in reducing the effects of the disease. Web site: http://www.delphion.com/details?pn=US05529786__ •
Protein which is characteristic of rheumatoid arthritis Inventor(s): Rosano; Carmen L. (23 Nancy Dr., Troy, NY 12180), Hurwitz; Charles (108 Mosher Rd., Delmar, NY 12054), Parhami; Nourollah (349 Torquay Blvd., Westmere, NY 12203), Hechemy; Karim (29 Pico Rd., Clifton Park, NY 12065) Assignee(s): none reported Patent Number: 4,645,748 Date filed: February 1, 1985 Abstract: Describes rheumatoid arthritis factor present in detectable amounts in rheumatoid arthritis patients, but not in patients with other arthritedes; preparation of antibodies to the factor; use of factor and antibodies to test for rheumatoid arthritis; and test kits for conducting the tests. Excerpt(s): Rheumatoid arthritis (RA) has been described as an unresolved systemic inflammation in which immune dysfunction and genetic susceptibility play roles. In earlier stages it is characterized by fluctuating remissions and exacerbations, and in later stages by a chronic granulatomous response (panus formation) leading to tissue destruction. The synovial membrane in RA has many of the characteristics of a hyperactive immunologically stimulated lymphoid organ and the ratio of T suppressor to T helper lymphocytes has been shown to be significantly reduced. Although a number of attempts have been made to implicate bacteria, viruses and mycoplasms as etiological agents, no specific causative agent has been clearly proven. It is possible that there is no specific etiological agent, and that the important agent or factor may be the result of an interplay of hereditary factors and physiological changes on non-specific inflammatory states. A great deal of work has been expended on the late, destructive phase of this disease in which anaphylactically induced leukotrienes and prostaglandins may play a chemotactic role in migration of neutrophils and macrophages into the rheumatoid synovium leading to destruction of bone and cartilage. Many attempts have been made to intervene between these events and the subsequent destructive phase occurring in the rheumatoid synovia. Web site: http://www.delphion.com/details?pn=US04645748__
Patents 393
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Recombinant antigen for diagnosing rheumatoid arthritis Inventor(s): Prakash; Ramesh K. (Salt Lake City, UT) Assignee(s): Research Corporation Technologies, Inc. (Tucson, AZ) Patent Number: 5,723,314 Date filed: April 10, 1996 Abstract: A method is described for diagnosing rheumatoid arthritis by providing a recombinant antigen (RAMA) and detecting rheumatoid arthritis-associated IgM antibodies against the RAMA antigen in patient sera. The RAMA antigen comprises SEQ ID NO:3 and peptides substantially homologous thereto. A purified and isolated DNA encoding the RAMA antigen and a transformed host containing the DNA are also disclosed. Excerpt(s): This invention relates to a method for diagnosing rheumatoid arthritis. More particularly, this invention relates to a method for objectively diagnosing rheumatoid arthritis by quantitative determination of the presence or absence of rheumatoid arthritis-associated antibodies in patient sera that react with a recombinant antigen. The invention also relates to the recombinant antigen and a molecular clone of the gene thereof. Rheumatoid arthritis is a chronic systemic rheumatic disease that affects a significant percentage of the population. Traditionally, it has been diagnosed subjectively through clinical observation and dominant complaints by a patient. P. Lipsky, Rheumatoid Arthritis, in Harrison's Principles of Internal Medicine 1423 (1987). Thus, clinical diagnosis of rheumatoid arthritis is subject to the skill of the diagnostician and the severity of disease symptoms in the patient. For an objective diagnosis of rheumatoid arthritis, the presence of rheumatoid factor (Rf) in the serum of rheumatoid arthritis patients is routinely determined. Rf is an autoantibody that binds to the constant region of IgG immunoglobulins. The standard test for determining the presence of Rf in blood is an aggregation test wherein Rf causes aggregation of IgG. Rf has been detected in approximately 70% of patients exhibiting clinical symptoms of rheumatoid arthritis. These patients are thus termed "seropositive." The remaining 30% are classified as having "seronegative" rheumatoid arthritis. Numerous conditions besides rheumatoid arthritis are associated with the presence of rheumatoid factor. Therefore, the presence of Rf does not establish a conclusive diagnosis of rheumatoid arthritis. An objective method of diagnosing rheumatoid arthritis that is more closely correlated with clinical diagnoses than is the presence of Rf in sera is needed. Ideally, such an objective diagnostic test would be quick and easy to perform and would not involve radioisotopes or be invasive to the patient. Web site: http://www.delphion.com/details?pn=US05723314__
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Substantially pure rheumatoid arthritis specific protein and an antibody against the same Inventor(s): Yamanaka; Naoki (Nagoya, JP), Yoshida; Makoto (Kawasaki, JP) Assignee(s): Medecs Co., Ltd. (Aichi, JP), Asahi Medical Co., Ltd. (Tokyo, JP) Patent Number: 4,742,157 Date filed: September 13, 1985 Abstract: A substantially pure rheumatoid arthritis specific protein (RASP) and an antibody against the rheumatoid arthritis specific protein (anti-RASP antibody) are
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disclosed. The RASP is found specifically in the serum or plasma of a patient suffering from rheumatoid arthritis, and may be detected using an anti-RASP antibody easily and effectively. Therefore, the anti-RASP antibody of the present invention is useful for the diagnosis of rheumatoid arthritis by the criterion of the presence of RASP. Excerpt(s): This invention relates to a substantially pure rheumatoid arthritis specific protein. The present invention also relates to an antibody against the rheumatoid arthritis specific protein. More particularly, the present invention is concerned with a protein specifically found in the plasma of a patient suffering from rheumatoid arthritis and an antibody specific for the antigenic determinant of the rheumatoid arthritis specific protein. Conventionally, the diagnosis of rheumatoid arthritis has been effected according to the criteria proposed by the American Rheumatism Association. However, such criteria depend on doctor's observations and dominant complaints by a patient, and therefore, such criteria are insufficient with respect to objectivity and quantitative analysis of the degree of rheumatoid arthritis. For the quantitative analysis of the degree of rheumatoid arthritis, the presence and amount of rheumatoid factor (RF), immune complex (IC) or C-reactive protein (CRP) in the serum or plasma of a patient have been determined. However, such substances are not necessarily specific for the plasma or serum of a patient suffering from rheumatoid arthritis, and therefore, such substances are not useful as a conclusive factor. Web site: http://www.delphion.com/details?pn=US04742157__ •
Treatment of arthritis disorders, rheumatoid arthritis and manifestations associated with rheumatoid disorders Inventor(s): Murray; James (Dorfet, GB), Snorrason; Ernir (Stigahlid 80, 105 Reykjavik, IS) Assignee(s): Snorrason; Ernir (Reykjavik, IS) Patent Number: 6,358,941 Date filed: May 3, 1999 Abstract: The present invention relates to the use of pharmaceutically acceptable cholinesterase inhibitors for the preparation of a pharmaceutical composition for the treatment or prophylaxis of arthritic disorders, including osteoarthritis, rheumatoid arthritis and other rheumatoid diseases such as Juvenile Arthritis, Systemic Lupus Erythematosis, Sjogren's Syndrome, Progressive Systemic Sclerosis, Polymyositis, Dermatomyositis, Ankylosing Spondilitis, Reiter's Syndrome, Psoriatic Arthritis, Relapsing Polychondritis, Relapsing Panniculitis, Crohn's Disease, Ulcerative Colitis, Heredity Complement Deficiencies, Collagen Vascular Diseases, Felty's Syndrome, rheumatological manifestations associated with bacterial and viral endocarditis or myocarditis and other rheumatological manifestations such as anaemia of chronic disorders. The invention also relates to a novel method of treatment or prophylaxis of such diseases and manifestations. Preferably, the cholinesterase inhibitors are selected from a group of nicotinic acetylcholinesterase inhibitors such as galantamine (the name of this drug was previously spelled galanthamine). Excerpt(s): The present invention relates to the use of pharmaceutically acceptable cholinesterase inhibitors of the preparation of a pharmaceutical composition for the treatment or prophylaxis of arthritic disorders, including osteoarthritis, rheumatoid arthritis and other rheumatoid diseases such as Juvenile Arthritis, Systemic Lupus Erythematosis, Sjogren's Syndrome, Progressive Systemic Sclerosis, Polymyositis,
Patents 395
Dermatomyositis, Ankylosing Spondilitis, Reiter's Syndrome, Psoriatic Arthritis, Relapsing Polychondritis, Relapsing Panniculitis, Crohn's Disease, Ulcerative Colitis, Hereditary Complement Deficiencies, Collagen Vascular Diseases, Felty's Syndrome, rheumatological manifestations associated with bacterial and viral endocarditis or myocarditis and other rheumatological manifestations such as anaemia of chronic disorders. The invention also relates to a novel method of treatment or prophylaxis of such diseases and manifestations. Preferably, the cholinesterase inhibitors are selected from a group of nicotinic acetylcholinesterase inhibitors such as galantamine (The name of this drug was previously spelled galanthamine). In the present description and claims, the term "rheumatoid" covers any of a variety of disorders marked by degeneration or metabolic derangement of the connective tissue structures of the body, especially the joints and related structures, including muscles, bursae (snyovial membranes), tendons and fibrous tissue. They are attended by pain, stiffness, or limitation of motion of these parts. Rheumatoid Arthritis is a chronic, recurrent systemic inflammatory disease primarily of the joints, usually polyarticular, marked by inflammatory changes in the snyovial membranes and articular structures and by atrophy and rarefaction of the bones. In late stages deformity and ankylosis develop. Extra-articular manifestations include vasculitis, atrophy of the skin and muscle, subcutaneous nodules, lymphadenopathy, splenomegaly, leukopaenia and often chronic anaemia. Web site: http://www.delphion.com/details?pn=US06358941__ •
Treatment of arthritis, including rheumatoid arthritis with.sup.166 Holmium radionuclide Inventor(s): Thornton; Alfred (New Hampton, NY), Lieberman; Ephraim (Suffern, NY), Bordoni; Maurice (Westtown, NY) Assignee(s): Cadema Medical Products, Inc. (Middletown, NY) Patent Number: 4,849,209 Date filed: January 28, 1987 Abstract:.sup.1/3 Holmium in a carrier metallic hydroxide aggregate is disclosed for the treatment of arthritis and, in particular, rheumatoid arthritis. The compound disclosed preferably has a particle size of 1 to 40 microns, Beta energy emissions in the range of 1.76-1.84 MeV, low levels of gamma ray emissions and a radioactive half-life of 26.8 hours. The preferred metallic hydroxide is selected from the group consisting of Ferric Hydroxide, Aluminum Hydroxide, Bismuth Hydroxide, Chromium Hydroxide, Cupric Hydroxide, Manganese Hydroxide and Stannous Hydroxide. Methods are also disclosed for the preparation of the compound, as well as for the methods of its administration to a patient in need thereof. Excerpt(s): The present invention relates to radioactive compounds, methods for the preparation thereof and a method for the treatment of arthritis, including rheumatoid arthritis. Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately six million of all arthritis sufferers are afflicted rheumatoid arthritis. Of these, over fifty percent (50%) ultimately will have involvement of the knee joint, over eighty percent (80%) will involve the hand joint and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow and shoulder. Rheumatoid arthritis is believed to be an autoimmune disease wherein parts of the body are attacked by antibodies manufactured in the body. These antibodies may be produced in response to viruses present in the body. While the mechanism for
396 Rheumatoid Arthritis
rheumatoid arthritis is not defined, it is a systemic disease. When the disease is active, the erythrocyte sedimentation rate (ESR) is elevated and the blood tests positive for rheumatoid factor. Web site: http://www.delphion.com/details?pn=US04849209__ •
Treatment of arthritis, including rheumatoid arthritis, with radioactive isotopes Inventor(s): Bordoni; Maurice E. (Westtown, NY), Thornton; Alfred K. (New Hampton, NY), Lieberman; Ephraim (Suffern, NY) Assignee(s): Cadema Medical Products, Inc. (Middletown, NY) Patent Number: 4,752,464 Date filed: June 7, 1985 Abstract: Treatment of rheumatoid arthritis by administering a radioactive compound to the inflamed synovium of the articular joint. The compound comprises an aggregate suspension having a radionuclide entrapped therein. The aggregate suspension is a ferric or aluminum hydroxide aggregate, and the radionuclide is selected from the group consisting of.sup.166 Holmium,.sup.153 Samarium,.sup.175 Ytterbium,.sup.169 Erbium, and.sup.176m Lutetium. The radionculide may also consist of.sup.51 Chromium. Suitable leakage inhibitors or agents to reduce leakage of the radionuclide from the articular joint is included as part of the chemical composition of the final drug form. Excerpt(s): The present invention relates to a radioactive compound, the methods for the preparation thereof and a method for the treatment of arthritis and, more particularly, radioactive compounds and a method for the treatment of rheumatoid arthritis. Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately nine percent (9%) of all arthritis sufferers are afflicted with a type of arthritis known as rheumatoid arthritis. Of these, approximately fifty-six percent (56%) ultimately will have involvement of the knee joint, eighty-seven percent (87%) of the hand joint and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow and shoulder. The source of disability for the sufferer of rheumatoid arthritis is an inflammatory response, of unknown origin, in the synovium, or lining, of the afflicted joint. This chronic inflammation, or synovitis, leads to pannus formation and, eventually, enzymatic destruction of the joint cartilage. Web site: http://www.delphion.com/details?pn=US04752464__
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Treatment of arthritis, including rheumatoid arthritis, with the radionuclide, tin SN121 Inventor(s): Bordoni; Maurice E. (R.D. 1, Box 680, Westtown, NY 10998), Thornton; Alfred K. (Box 500 Lower Rd., New Hampton, NY 10958), Lieberman; Ephraim (1 Victory Rd., Suffern, NY 10901) Assignee(s): none reported Patent Number: 4,906,450 Date filed: March 26, 1987 Abstract: The radionuclide Tin, Sn-121 in a carrier hydroxide aggregate is disclosed for the treatment of arthritis and, in particular, rheumatoid arthritis of the hands, the
Patents 397
interphalangeal joints of the fingers and the metacarpal joints of the hand.The radioactive compound disclosed preferably has a particle size of <90 microns. The beta energy emission associated with Tin, Sn-121 has an energy of 0.38 meV. There are no gamma photons emited during the decay of Tin, Sn-121 to stable Antimony Sb-121. The half life of Tin, Sn-121 is 27.06 hours.The method of preparation of the compound is disclosed along with the method of administration to the patient in need thereof. Excerpt(s): The present invention relates to the use of a compound, radioactive Tin, Sn121, for treating arthritis, in particular rheumatoid arthritis of the fingers (interphalangeal joints and the metacarpal joints of the hand). Methods for the preparation of the compound are described. Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately six million (6,000,000) people are afflicted with rheumatoid arthritis. Of these, over eighty percent (80%) ultimately will have involvement of the hand joint, over fifty percent (50%) will involve the knee joint, and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow, and shoulder. Rheumatoid arthritis is believed to be an autoimmune disease wherein parts of the body are attacked by antibodies manufactured in the body. These antibodies may be produced in response to viruses present in the body. While the mechanism for rheumatoid arthritis is not known, it is a systemic disease. When the disease is active, the erythrocyte sedimentation rate (ESR) is usually elevated and the blood tests usually positive for rheumatoid factor. Web site: http://www.delphion.com/details?pn=US04906450__ •
Treatment of autoimmune diseases such as rheumatoid arthritis with suppressor factor Inventor(s): Lau; Catherine Y. (Unionville, CA) Assignee(s): Ortho Pharmaceutical (Canada) Ltd. (CA) Patent Number: 4,705,687 Date filed: June 17, 1985 Abstract: Method of treating autoimmune diseases such as rheumatoid arthritis by administration of a suppressor factor obtained in the supernatant of a human cell line. A particular human cell line is CEM which has survived treatment with 6-thioguanine. Excerpt(s): The mammalian immune system includes a complex array of organs, cells and soluble products of cells. Organs involved in the immune system include the bone marrow, spleen and lymph nodes; a wide variety of cells populate the immune system and this includes macrophages, granulocytes and T and B lymphocytes. Examples of soluble products produced by immune system cells include antibodies (produced by B lymphocytes) and lymphokines (produced by T-lymphocytes). The latter play an important role in regulating the immune system. (a) identification of substances or cells within the body to determine whether they are "self" or "non-self". (b) communication between cells to facilitate a response to "non-self" entities. Web site: http://www.delphion.com/details?pn=US04705687__
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Treatment of rheumatoid arthritis and related diseases Inventor(s): Wyburn-Mason; Roger (Richmond Surrey, GB2) Assignee(s): Simoons; John R. A. (Summit, NJ) Patent Number: 4,119,723 Date filed: July 8, 1977 Abstract: It is believed that rheumatoid arthritis and related collagen and auto-immune diseases are an infection and that various species of free-living (limax) amoebae are the aetiological agent of these diseases. It has been discovered that tinidazole and related compounds, antimycotic drugs with anti-protozoal activity, are effective for the treatment of rheumatoid arthritis and other collagen and auto-immune (rheumatoid) diseases. Excerpt(s): Men and other animals are continually exposed to infection and re-infection by various species and strains of free-living limax amoebae which can be detected in the faeces, nasopharynx and bronchi. In all parts of the world they form part of the environment. Experimentally in animals they induce changes like those of collagen and auto-immune diseases and are characterized by vasculitis, myosotis, hepatitis, pyelitis and spelenomegaly. They can often be seen in the tissues of animals. Such animals shown lymphadenopathy with an appearance like that of human Hodgkin's disease or a state like that of advanced malignant disease. These organisms may also be recovered from all the tissues of cases of collagen and auto-immune diseases and from human and many animal tumors and may also occur in the tissues of apparently healthy individuals. They cannot be identified in ordinary histological sections, but can be demonstrated by immunofluorescent methods. The definite cause of rheumatoid arthritis is presently unknown. Rheumatoid arthritis is a crippling disease, characterized by the inflammation of several joints of the body, with swelling, pain and stiffness. Rheumatoid arthritis is a disorder that afflicts about fifteen million people in the Western World alone. Successful early treatment may avert the destructive, deforming phase of the disease. Therapy has been directed largely at non-specific suppression of inflammatory and immunoligic processes. Aspirin is the cornerstone of therapy for rheumatoid arthritis and can reduce synovial inflammation, improve function and reduce pain in a majority of patients in view of its analgesic action. Widespread interest in rheumatoid arthritis arose when Hench (1949) introduced the use of cortisone in treatment. Chemical compounds which have been commonly used in treating rheumatoid arthritis are corticosteroids, gold salts, antimalarial drugs, immunosuppressive agents and a whole range of so-called non-steroidal drugs, e.g. indomethacin, phenylacetic acid (Ibuprofen), propionic acid (Naproxen) and DPenicillamine. Most of these drugs bring temporary relief to the arthritic patient but present the danger of side effects and the physician has to balance the potential benefit against the risks. However, arthritis reoccurs following withdrawal of such chemical treatment. For many years rheumatoid arthritis was considered to be an infection (Hollander et al., 1960; Robinson, 1967), but with the advent of the concept of autoimmunity this idea lost favor. Such a view has recently been revived (Lancet, 1970, 2, 303) and is supported by many observations. It is highly likely that the limax amoebae, found in all the collagen and auto-immune diseases, may well be the aetiological agent of these conditions and that anti-protozoal drugs may help by their action on these organisms. The use of a bis-phenyl (2-halophenyl)-1-imidazolylmethane and clotrimazole for treatment of Rheumatoid Arthritis is disclosed in my U.S. patent application Ser. No. 700,914 filed June 29, 1976. It has also been suggested to use a nitroimidazole in the treatment of rheumatoid arthritis in the Journal of Tropical
Patents 399
Medicine and Hygiene (vol. 75) pgs. 64 to 66 March 1972. It is believed that the nitro group in the imidazole ring is related to metronidiazole which is not effective in the treatment of rheumatoid arthritis. Web site: http://www.delphion.com/details?pn=US04119723__ •
Treatment of rheumatoid arthritis by oral administration of pooled human immunoglobulin Inventor(s): Weisbart; Richard (Los Angeles, CA) Assignee(s): Research Corporation Technologies, Inc. (Tucson, AZ) Patent Number: 6,090,380 Date filed: May 22, 1995 Abstract: Pooled human immunoglobulin may be administered orally to rheumatoid arthritis patients to treat the rheumatoid arthritic condition of those patients. Oral administration of pooled human immunoglobulin can result in significant clinical improvement in the level of disease activity in patients with rheumatoid arthritis. Excerpt(s): The present invention relates generally to the treatment of rheumatoid arthritis. More particularly, the invention relates to the treatment of rheumatoid arthritis by oral administration of pooled human immunoglobulin. The publications and other reference materials referred to herein to describe the background of the invention and to provide additional detail regarding its practice are hereby incorporated by reference. Rheumatoid arthritis ("rheumatoid arthritis") is a systematic inflammatory disease that commonly affects the joints, particularly those of the hands and feet. The onset of rheumatoid arthritis can occur slowly, ranging from a few weeks to a few months, or the condition can surface rapidly in an acute manner. Web site: http://www.delphion.com/details?pn=US06090380__
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Treatment of the articular symptoms of rheumatoid arthritis Inventor(s): Cagnoni; Mario (178, Via Bolognese, 50139 Firenze, IT) Assignee(s): none reported Patent Number: 5,609,877 Date filed: November 30, 1994 Abstract: The present invention relates to the employment of melatonin in the preparation and use of pharmaceuticals effective in the treatment of the articular symptoms of rheumatoid arthritis. Excerpt(s): The present invention concerns the field of rheumatology and more precisely relates to the use of melatonin (MLT) in the treatment of articular inflammatory symptoms. The most common of the diseases characterized by acute and chronic inflammation of the joints is rheumatoid arthritis. As regards its etiology, none of the hypotheses proposed over time has ever found persuasive confirmation. Recently the etiopathogenetic hypothesis according to which the disease can be ascribed to the group of forms of hypersensitivity (the immune theory) has won the greatest agreement. In the therapy of this disease, pharmaceuticals of various types are used with the object of controlling the inflammatory process and also to remedy the damage that the
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inflammatory process itself caused to the osteocartilaginous structures. Among these we have gold salts, antimalarials, penicillamine, and furthermore all the analgesic and steroid and nonsteroid anti-inflammatory pharmaceuticals. In particular, the symptomatic therapy is carried out by resorting to antiphlogistic drugs (nonsteroidal anti-inflammatory agents and cortisone compounds) and the base therapy using synthesized antimalarials, penicillamine, azathioprine, cyclophosphamide, gold salts, etc. Web site: http://www.delphion.com/details?pn=US05609877__ •
Use of 6-halo-4-quinolone compounds and pharmaceutical compositions thereof for the preparation of a medicament for the therapeutical application in rheumatoid arthritis Inventor(s): Caruso; Innocenzo (Via Wittgens, 5, 20100 Milan, IT) Assignee(s): none reported Patent Number: 4,978,661 Date filed: August 11, 1989 Abstract: The present invention relates to the use of 6-halo-4-quinolone derivatives and pharmaceutical compositions comprising them as active ingredient, for the preparation of a medicament for the therapeutical application in rheumatoid arthritis.Quinolone derivatives can be intra-articularly administered and act on different points of the pathological process of rheumathoid arthritis without local and general toxicity. Excerpt(s): The present invention relates to the use of 6-halo-4-quinolone compounds and to pharmaceutical compositions thereof for the preparation of a medicament useful in therapy of rheumatoid arthritis. Rheumatoid arthritis (RA) is a primary illness of the articulations (synovitis) that may cause systemic complications, very often later in its clinical course. The pathologic process is characterized by an unceasable proliferation of the synovial tissue causing the formation of the so called "pannus" which yields the gradual destruction of the articulation by invading the cartilage and subchondral bone. It is generally accepted that a genetic predisposition may exist which causes an abnormal reactivity in these patients and/or a loss of the mechanisms of tissue control. It has been hypothized that rheumatoid inflammatory process, started by a yet unknown etiologic agent, becomes self-perpetuating either for the unability of the patient to get rid of the exogenous antigen inducing it (retained antigen), or for an induced autoimmunization against a structure of the same organism (Ig G, Collagen proteins, etc.), such structure being degraded during an aspecific inflammation. Web site: http://www.delphion.com/details?pn=US04978661__
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Use of a cytokine regulatory agent to treat rheumatoid arthritis Inventor(s): Girten; Beverly E. (San Diego, CA), Tuttle; Ronald R. (Escondido, CA) Assignee(s): Trega Biosciences, Inc. (San Diego, CA) Patent Number: 5,741,774 Date filed: September 27, 1996 Abstract: The present invention relates to the use of a cytokine regulatory agent to reduce the severity of rheumatoid arthritis.
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Excerpt(s): This invention relates generally to the fields of medicine and immunopathology and, more specifically, to methods of using a cytokine regulatory agent to reduce the severity of rheumatoid arthritis in an individual. Cytokines are a class of proteins produced by macrophages and monocytes in response to viral or bacterial infection and in response to T cell stimulation during an immune response. Cytokines are normally present in very low concentrations in a tissue and mediate their effects through binding to high affinity receptors on specific cell types. The cytokines, including TNF, IL-1, IL-2, IL-6 and IL-8, mediate host defense responses, cell regulation and cell differentiation. These cytokines can induce fever in a subject, cause activation of T and B cells and affect the levels of other cytokines, which result in a cascade effect whereby other cytokines mediate the biological action of the first cytokine. Web site: http://www.delphion.com/details?pn=US05741774__ •
Use of beta.sub.2 antagonists in the treatment of inflammatory diseases, in particular, rheumatoid arthritis Inventor(s): Levine; Jon D. (San Francisco, CA), Basebaum; Allan I. (San Francisco, CA) Assignee(s): The Regents of the University of California (Berkeley, CA) Patent Number: 4,908,387 Date filed: June 6, 1988 Abstract: A method of treating inflammation and joint deterioration in mammals which comprises administering a therapeutically effective amount of a selective beta.sub.2 adrenergic receptor antagonist. The method is particularly useful for the treatment of rheumatoid arthritis in humans. Excerpt(s): This invention concerns the use of selective beta.sub.2 antagonists as active agents in the treatment of inflammatory diseases, particularly rheumatoid arthritis. Inflammatory diseases, in particular rheumatoid arthritis, have been treated with a wide variety of compounds representing many different structural and pharmacologic classes, including, for example, aspirin and related compounds, non-steroidal anti inflammatory agents (NSAIDS) such as indomethacin, naproxen, ibuprofen and the like, corticosteroids, immunosuppressive, opiates, antimalarials such as hydroxychloroquine and chloroquine, cytotoxics such as cyclophosphamide, chlorambucil and azathioprine, penicillamine and its derivatives, and heavy metals such as the gold salts. No representative of any of these classes is regarded as ideal. Moreover, of these, only penicillamine, some gold compounds and possibly the corticosteroids in high doses have been shown to significantly suppress the progress of rheumatoid arthritis disease (disease modification). The magnitude of thee effects, however, are small, and decrease with time. Further, these compounds possess such severe toxicities that they are reserved for patients whose disease progresses rapidly inspite of treatment with less toxic agents. Finally, all of the drugs available for treating inflammatory disease, whether for symptomatic relief or disease modification, possess side effects which make drug tolerance a serious problem for many patients. The available therapies are especially poorly tolerated by aged individuals, in whom inflammatory diseases are particularly prevalent and debilitating. None of the drugs presently available for treating inflammatory disorders are known to act via the nervous system. However, researchers have recently noted an apparent contribution of the sympathetic nervous system to the proliferation of inflammatory conditions and processes. It has been reported that dogs chronically maintained on beta adrenergic agonists develop a rheumatoid arthritis like syndrome [Vyden et al. Arthritis Rheum. 14, 420, (1971)]. The
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inventors of the present invention, in conjunction with colleagues, have reported on studies showing that sympathectomy markedly attenuates the signs of inflammation and severity of joint injury in rats with experimentally induced arthritis and that intracerebroventricular administration of morphine, which is known to decrease sympathetic tone, decreases arthritic severity [Levine et al., J.Neurosci. 6, 3423-3429 (1986)]. The inventors have also reported that regional sympathetic blockade with guanethidine reduces pain and increases pinch strength in patients with active rheumatoid arthritis [Levine et al., J. Rheumatol., 13, 1040-1043 (1986)]. Finally, propranolol, a beta adrenergic blocker, has been shown, in very high doses that produce significant toxicity, to decrease signs and symptoms of inflammation, in patients with active rheumatoid arthritis; suppression of joint deterioration was not shown. [Kaplan et al., Arthritis Rheum. 23, 253-255 (1980)]. Web site: http://www.delphion.com/details?pn=US04908387__ •
Use of interleukin-4 (IL-4) to treat rheumatoid arthritis Inventor(s): Arai; Ken-ichi (Palo Alto, CA), Mosmann; Timothy (Atherton, CA), Yokota; Takashi (Palo Alto, CA), Rennick; Donna (Los Altos, CA), Lee; Frank (Palo Alto, CA) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,951,973 Date filed: June 6, 1995 Abstract: A method of treating rheumatoid arthritis comprising administering human Interleukin-4 (IL-4) to an individual afflicted with the disease. The IL-4 is administered with a pharmaceutically acceptable carrier in a dose ranging from 1.mu.g to 100 mg. Excerpt(s): This invention relates generally to the application of recombinant DNA technology to elucidate the control mechanisms of the mammalian immune response and, more particularly, to the isolation of nucleic acid clones coding for polypeptides capable of exhibiting B-cell, T-cell, macrophage and mast cell stimulatory activity, as well as colony stimulating factor enhancing activity. Recombinant DNA technology refers generally to the technique of integrating genetic information from a donor source into vectors for subsequent processing, such as through introduction into a host, whereby the transferred genetic information is copied and/or expressed in the new environment. Commonly, the genetic information exists in the form of complementary DNA (cDNA) derived from messenger RNA (mRNA) coding for a desired protein product. The carrier is frequently a plasmid having the capacity to incorporate cDNA for later replication in a host and, in some cases, actually to control expression of the cDNA and thereby direct synthesis of the encoded product in the host. For some time, it has been documented that the mammalian immune response is based on a series of complex cellular interactions, called the "immune network." Recent research has provided new insights into the inner workings of this network. While it remains clear that much of the response does, in fact, revolve around the network-like interactions of lymphocytes, macrophages, granulocytes and other cells, immunologists now generally hold the opinion that soluble proteins (e.g., the so-called "lymphokines") play a critical role in controlling these cellular interactions. Thus, there is considerable interest in the isolation, characterization, and mechanisms of action of cell modulatory factors, an understanding of which should yield significant breakthroughs in the diagnosis and therapy of numerous disease states. Web site: http://www.delphion.com/details?pn=US05951973__
Patents 403
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Use of rifamycin SV and its related salts in the treatment of rheumatoid arthritis, and related formulations suited for the purpose Inventor(s): Molteni; Luigi (Malnate, IT), Caruso; Innocenzo (Milan, IT), Montrone; Franco (Milan, IT) Assignee(s): Dr. L. Zambeletti S.p.A. (Milan, IT) Patent Number: 4,312,866 Date filed: July 7, 1980 Abstract: The invention concerns new salts of rifamycin SV and a new use of rifamycin SV in the treatment of rheumatoid arthritis and analogous affections, by intra-articular injection of the sodium salt of rifamycin SV or, better, of salts of said anti-biotic with basic aminoacid, e.g. with arginine, lysine or histidine. Excerpt(s): The present invention concerns a new use of rifamycin SV in the treatment of rheumatoid arthritis, and analogous pathologic affections, by an intra-articular injection of rifamycin SV itself, preferably in a salified form. All the operations pertaining to the preparation of the salts as per re, with inclusion of their purification, their formulation into pharmaceutical dosage forms suited for its administration, and/or of their packaging into containers suited for administration shall be covered by the term "use", to be intended according to the present invention. Rifamycin SV has been used for over 15 years in human and veterinary medicine as a therapeutic agent in all the range of infections due to Gram-positive and Gram-negative pathogens, Mycobacterium tuberculosis and Mycobacterium leprae. 8. leprosy. Web site: http://www.delphion.com/details?pn=US04312866__
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Use of selenium-containing compounds for negating the toxic effects of gold compounds used in the treatment of rheumatoid arthritis, and a novel seleniumcontaining gold compound and use thereof as an anti-rheumatoid arthritis medicine Inventor(s): Dumas; Phillip E. (137 Louise Dr., Morrisville, PA 19067), Stockel; Richard F. (457 Rolling Hills Rd., Bridgewater, NJ 08807) Assignee(s): none reported Patent Number: 4,680,286 Date filed: April 9, 1985 Abstract: The toxic effects of gold compounds used in the treatment of rheumatoid arthritis can be negated by the use of a selenium-containing compound. A new selenium-containing gold compound has been found to be useful as a gold compound type anti-rheumatoid arthritis medicine which can self-detoxify gold toxicity. Excerpt(s): The present invention relates to a method of negating the toxic effects of gold compounds. More particularly, the present invention relates to a method of negating the toxic effects of gold compounds used in the treatment of rheumatoid arthritis, which method comprises administering to a patient a selenium-containing compound. The present invention is also concerned with a novel selenium-containing gold compound which can be effectively used as a so-called gold compound type anti-rheumatoid arthritis medicine which can self-detoxify gold toxicity. The most common form of chronic inflammatory arthritis is rheumatoid arthritis, which is characterized by symmetrical inflammatory polyarthritis, morning stiffness and positive rheumatoid factor. Over more than 100 diseases have been classified as arthritis, in addition to
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chronic inflammatory arthritis. Each decision to treat with a drug requires careful therapeutic weighing of the hazards and the benefits of the drug versus the disability caused by the symptoms. Various groups of drugs useful for arthritis include salicylates, indole derivatives, propionic acid derivatives, phenylbutazone and oxyphenbutazone, penicillamine, corticosteroids, cytotoxic drugs and anti-gout agents. For an excellent review on these anti-arthritic drugs, a review article written by J. A. Markenson, appearing in Drug Therapy, January, 1981, page 45 dives a comparative overview of these types of classes of drugs. As mentioned above, there are various drugs effective in the treatment of arthritis, however, gold compounds used in gold therapy are most effective as anti-rheumatoid agents, and the gold therapy should be considered in patients with active disease who fail to respond to the plethora of drugs previously mentioned to reduce inflammation. Web site: http://www.delphion.com/details?pn=US04680286__ •
Use of zofenopril for the treatment of rheumatoid arthritis Inventor(s): Devlin; Richard G. (Sea Girt, NJ) Assignee(s): E. R. Squibb & Sons, Inc. (Princeton, NJ) Patent Number: 4,855,315 Date filed: September 2, 1988 Abstract: Zofenopril, and pharmaceutically acceptable salts thereof, can be used for the treatment of rheumatoid arthritis. Excerpt(s): Rheumatoid arthritis is a lifelong, crippling, multisystem disease whose principal manifestation is joint inflammation. The prevalence of definite rheumatoid arthritis in the United States is approximately 1 percent (2,400,000 individuals). This estimated prevalence increases to 3 percent (7,200,000 individuals) when a more liberal definition of disease as specified by the American Rheumatism Association ("probable" and "possible" rheumatoid arthritis) is applied. In the majority of individuals the disease is characterized by a fluctuating and variable course with lifelong periods of exacerbation and regression, but with ever worsening joint deformity and systemic disability. Approximately 10 percent of patients develop only a short-lived inflammatory process which remits spontaneously without permanent residua, while at the opposite end of the spectrum another 10 percent experience a relentlessly progressive disease leading rapidly to marked deformity and disability. The principal manifestation of rheumatoid arthritis is joint inflammation and deformity, usually accompanied by constitutional symptoms such as weakness, easy fatigability, anorexia or weight loss. Approximately 10-20 percent of individuals with definite rheumatoid arthritis experience significant extra-articular manifestation including vasculitis, skeletal muscle weakness and atrophy, polyneuropathy, pleuropulmonary disease, pericarditis or hematologic abnormalities. Chemotherapeutic agents available for the treatment of rheumatoid arthritis are characterized by low efficacy and high toxicity. These agents fall into categories including steroids, nonsteroidal anti-inflammatory agents (NSAID's) and disease modifying anti-rheumatoid drugs (DMARD's). The NSAID's which include salicylates, as well as ibuprofen, fenoprofen, naproxen, piroxicam, tolmetin, indomethacin, sulindac, meclofenamate and others are primariy cycloxygenase inhibitors, inhibiting production of prostaglandins, prostacycline and thromboxanes. Thus, they all produce nonspecific analgesic, anti-inflammatory and antipyretic effects and are prescribed for the control of a variety of inflammatory states. Although they are perceived to be quite potent, in fact none have been demonstrated to be more effective
Patents 405
than aspirin in the treatment of rheumatoid arthritis. NSAID's are generally prescribed as first line therapy for this condition and are administered episodically for control of acute exacerbation of disease. Patients commonly develop tachyphylaxis or therapeutic tolerance to these agents over time and it is common practice for individuals to be switched frequently from one to another agent in the group. It is unclear whether such decreased efficacy is a function of disease progression or physiologic tolerance. Despite their status as first line treatment for rheumatoid arthritis, the NSAID's are associated with a wide spectrum of toxic side effects, especially at the doses needed to control rheumatoid arthritis. All are associated with gastrointestinal irritation (and bleeding), azotemia, platelet dysfunction, liver function abnormalities, bone marrow depression and exacerbation of allergic conditions such as rhinitis or asthma. Although the incidence of each of these effects varies somewhat with the specific agent, elderly patients receiving diuretics, common in populations with rheumatoid arthritis, may be at higher than average risk for such phenomena. Web site: http://www.delphion.com/details?pn=US04855315__ •
Vaccine compositions and methods useful in inducing immune protection against arthritogenic peptides involved in the pathogenesis of rheumatoid arthritis Inventor(s): Albani; Salvatore (Encinitas, CA), Carson; Dennis A. (Del Mar, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,153,200 Date filed: June 30, 1998 Abstract: Vaccine compositions useful in inducing immune protection in a host against arthritogenic peptides involved in the pathogenesis of rheumatoid arthritis are disclosed. Each vaccine composition provides antigenic dnaJp1 peptide (by including the peptide or a polynucleotide which encodes the peptide) and, optionally, other peptide fragments of the microbial dnaJ protein and/or human homologs thereof. Methods for identifying persons who are predisposed to develop rheumatoid arthritis and methods for use of the inventive vaccines are also disclosed. Excerpt(s): The invention relates to the control and prevention of autoimmune disease, in particular rheumatoid arthritis. More specifically, the invention relates to methods and reagents which reduce or prevent the response of a host to arthritogenic peptides which include an amino acid sequence (Q(K/R)RAA) that is homologous to a sequence contained in certain HLA proteins. In humans, autoimmune diseases such as rheumatoid arthritis tend to be associated with particular HLA specificities. Rheumatoid arthritis (RA) in particular is presently believed to be associated on a genetic level with the Class II HLA haplotypes DW4, DW14, DW15 (all with DR4 specificity) and/or DR1. Each of these haplotypes include an amino acid sequence which is commonly referred to as the "susceptibility sequence" (hereafter, "RA susceptibility sequence"; see, SEQ.ID.NOs: 1 and 2). The RA susceptibility sequence is known to vary at one amino acid; to wit, QRRAA and QKRAA (hereafter, "Q(R/K)RAA"). More than 90% of adult patients with seropositive RA have also been found to have HLA DR antigens with the RA susceptibility sequence in the third hypervariable region of the molecule. The RA susceptibility sequence has not been implicated in the onset of juvenile RA (JRA), except in patients suffering from severe, seropositive JRA. The QRRAA variant of the susceptibility sequence has been identified on HLA haplotypes DW14, DW15 and DR1. The QKRRA variant has been identified on HLA haplotype DW4. Highly conserved homologs of the variants have also been identified in the Epstein-Barr virus glycoprotein
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gp110, as well as the dnaJ heat shock proteins from Escherichia coli, as well as the bacterial species Klebsiella, Proteus, Salmonella, and Lactococcus. Web site: http://www.delphion.com/details?pn=US06153200__ •
Vinblastine in rheumatoid arthritis Inventor(s): Schinitsky; Michael R. (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 4,208,414 Date filed: May 14, 1979 Abstract: Vinblastine (vincaleucoblastine, VLB) and other anti-mitotic vinca alkaloid is useful in the treatment of rheumatoid arthritis and related diseases, alone or in combination with an anti-inflammatory agent. Excerpt(s): Vinblastine (U.S. Pat. No. 3,097,137) has been employed for a number of years as an oncolytic agent particularly useful in the treatment of Hodgkin's Disease and other lymphomas. It is generally administered by the intravenous route to patients suffering from one of these diseases. There has been a sparse amount of research work reported involving vinblastine, or other oncolytic vinca alkaloids and their derivatives, directed toward their physiological action in non-neoplastic conditions. For example, vinblastine has been used to induce leucopenia in experimental animals and the effect of that leucopenia on other conditions studied. Phelps and McCarty, writing in J. Exp. Med., 124 115 (1966), induced a gouty arthritis type of inflammation in dogs by the injection into the joint of microcrystalline sodium urate. An acute inflammatory reaction was ordinarily produced, but, in dogs pretreated with vinblastine at such a dose level that there was a profound leukocyte depletion, significant phagocyte accumulation was prevented and the inflammatory response was almost completely abolished. This finding led the authors to the conclusion that, in the particular experimental model, the polymorphonuclealeukocyte was necessary to the urate-crystal induced inflammation. Chang and Gralla, writing in Arthritis and Rheumatism, 11, 145 (1968), investigated the possibility that the effects of vinblastine on joint inflammation found by Phelps and McCarty were mediated by means other than the reduction in the number of polymorphs. These authors produced a leucopenia in dogs by using rabbit-anti-dogpolymorphonuclear serum. It was their conclusion that their findings were in accord with those of Phelps and McCarthy as regards the role of a vinblastine-induced leucopenia in preventing inflammation subsequent to the injection of mycrocrystalline urate into canine joints. Floresheim, et al. writing in Agents and Actions, 3 24 (1973) induced an acute arthritis in pigeons or chickens by the injection of microcrystalline sodium urate into the intertarsal joint. They found no inhibition of the arthritic response from a number of agents including both vinblastine and vincristine. Fitsgerald, et al., Pharmacology, 6, 265 (1971) used a different model--the sodium urate-induced paw swelling in mice. The authors found that various anti-mitotics including vinblastine and vincristine produced a significant depression of paw swelling at similar dose levels. The effects of the various anti-mitotic agents did not seem to bear any relation to their antimitotic potency. T. Y. Shen, in an article titled "The Expanding Vistas of Non-acidic Anti-arthritic Agents" in Drugs in Experimental Clinical Research Vol II (1) (1977) speculates that one approach, among many, for regulation of the immuno-pathology of arthritis would be to investigate the effect of selective membrane modulators upon this disease. According to Shen, "[p]hagocytosis and the function of membrane receptors and enzymes are subject to the regulation by the fluidity of the bi-layer membrane by the
Patents 407
submembrane structures, microtubules and microfilaments. " He reports that among the classical inhibitors of microtubules are included the vinca alkaloids, vinblastine and vincristine, the anti-tumor drug, maytensine, phodphyllotoxin and colchicin. Finally, in June, 1977, a question was raised as to whether it would be useful to use vinblastine in the treatment of systemic sclerosis (Abstracts of the 14th International Congress of Rheumatism--June 26, 1977, San Francisco, California--Abstract No. 661). The authors concluded that it would be. At the same meeting, a paper was presented (Abstract No. 426) concerning the effect of the intravenous administration of vinblastine on inflammation induced by the injection of pulverized calcium pyrophosphate dihydrate crystals into the pleural cavity. The authors concluded that vinblastine may have a suppressive effect on the inflammation thus induced. This invention provides a method of treating rheumatoid arthritis which comprises administering to a mammal suffering from rheumatoid arthiritis and in need of treatment, an amount of a vinca-derived oncolytic agent, specifically vinblastine, effective to arrest the progress of the disease. Administration can be parenteral, specifically by the intrevenous route, or, preferably, oral. The amount of vinblastine administered varies according to the route employed. For example, by the intravenous route, a dose of 0.1 to 0.5 mg./kg. can be employed (3.7 to 18.5 mg. per meter squared), whereas the oral dosage would be roughly ten times as great (1 to 5 mg./kg.). The drug is customarily administered once (as contrasted with the daily, every third day, or weekly dosage regimen when vinblastine is used to treat Hodgkin's Disease or related neoplasms). If required, the dosage can be repeated, but not more often than every two weeks or once a month in order to avoid cumulative sideeffects. In a second aspect of this invention, vinblastine is administered in conjunction with an anti-inflammatory agent of the profen class including ibuprofen, (.+-.).alpha.methyl-4-(2-methylpropyl)benzeneacetic acid; carprofen,.alpha.-methyl-6chlorocarbazole-2-acetic acid; cicloprofen,.alpha.-dl-2-methylfluorene-2-acetic acid; fenoprofen, dl-.alpha.-methyl-3-phenoxybenzeneacetic acid; indoprofen,.alpha.-methyl4-(1,3-dihydro-1-oxo-2H-isoindolyl-2-yl)benzenacetic acid; ketoprofen,.alpha.-methyl-3benzoylbenzeneacetic acid; naproxyn, (.+-.).alpha.-methyl-6-methoxy-2naphthaleneacetic acid; pirprofen, dl-.alpha.-methyl-3-chloro-4-(3-pyrrolidinol-1yl)benzeneacetic acid; suprofen, dl-.alpha.-methyl-4-(thienylcarbonyl)-benzeneacetic acid and benoxoprofen, dl-.alpha.-methyl-2-(p-chlorophenyl)benzoxazoleacetic acid and the like drugs. Other non-profen type anti-inflammatory drugs such as indomethacin can also be used advantageously with VLB and like drugs to treat rheumatoid arthritis. Such combinations of drugs, a vinca alkaloid and an anti-inflammatory agent, are particularly valuable because the primary effect of vinblastine and related alkaloids is to arrest further progress of the rheumatoid process and administration of the drug afords little if any symptomatic relief whereas, by contrast, the chief effect of the antiinflammatory drug is to alleviate the arthritic symptoms but with little or no hindrance to the progress of the arthritic process. Web site: http://www.delphion.com/details?pn=US04208414__
Patent Applications on Rheumatoid Arthritis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take
10
This has been a common practice outside the United States prior to December 2000.
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several years.) The following patent applications have been filed since December 2000 relating to rheumatoid arthritis: •
CD44 splice variant associated with rheumatoid arthritis Inventor(s): Golan, Itshak; (Ashdod, IL), Nedvetzki, Shlomo; (Jerusalem, IL), Naor, David; (Jerusalem, IL) Correspondence: COOLEY GODWARD, LLP; 3000 EL CAMINO REAL; 5 PALO ALTO SQUARE; PALO ALTO; CA; 94306; US Patent Application Number: 20030108984 Date filed: December 7, 2001 Abstract: A novel variant mRNA transcript of CD44 found in synovial cells of rheumatoid arthritis (RA) patients is described. This novel transcript contains the known CD44 constant and variant exons but also comprises three additional nucleotides (CAG) that are transcribed from the end of the intron bridging Exon v4 to Exon v5 and are inserted at the 5' end of Exon v5. This extra CAG sequence results in the insertion of a new codon for the amino acid alanine. The novel CD44 transcript found to date in eighteen RA patients and not found in healthy (non-RA) individuals, is useful in the diagnosis, prognosis, prevention and treatment of RA, of other diseases in which the variant CD44 transcript is involved and possibly in disorders and diseases which involve cells expressing other forms of the CD44 protein. Excerpt(s): This application is a continuation-in-part of International Application PCT/IL00/00326, filed Jun. 7, 2000, which claims priority to Israeli application No. 130356, filed Jun. 8, 1999, and Israeli application 133647, filed Dec. 21, 1999. All of which applications are incorporated by reference herein. The present invention concerns a novel nucleic acid coding sequence, vectors and host cells comprising said sequence, amino acid sequences encoded by, said sequence, antibodies reactive with said amino acid sequences and pharmaceutical compositions comprising any of the above. The invention also concerns methods for the diagnosis, prognosis, prevention and treatment of various diseases, mainly infectious and other inflammatory diseases and autoimmune diseases, and cancer. Aune, T. M., et al., Published EP Application No. 501233 (1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Chronic rheumatoid arthritis therapy containing IL-6 antagonist as effective component Inventor(s): Kishimoto, Tadamitsu; (Osaka, JP), Mihara, Masahiko; (Gotenba-shi, JP), Moriya, Yoichiro; (Gotenba-shi, JP), Oshugi, Yosiyuki; (Gotenba-shi, JP) Correspondence: Harold C. Wegner; FOLEY & LARDNER; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20010001663 Date filed: January 9, 2001 Abstract: There is provided a synovial cell growth inhibitor, or a pharmaceutical composition for treatment of chronic rheumatoid arthritis based on the synovial cell growth inhibitor.The pharmaceutical composition for treatment of chronic rheumatoid arthritis or synovial cell growth inhibitor contains an IL-6 antagonist, such as IL-6 antibody or IL-6R antibody, as an effective component.
Patents 409
Excerpt(s): The present invention relates to a chronic rheumatoid arthritis therapy or synovial cell growth inhibitor comprising an interleukin-6 antagonist as an effective component. Chronic rheumatoid arthritis is a systemic chronic inflammatory disease in which abnormal growth of connective tissue, including synovial tissue, occurs in the joints (Melnyk et al., Arthritis Rheum. 33: 493-500, 1990). The joints of chronic rheumatoid arthritis patients have been shown to have marked growth of synovial cells, formation of a multilayer structure due to abnormal growth of the synovial cells (pannus formation), invasion of the synovial cells into cartilage tissue and bone tissue, vascularization toward the synovial tissue, and infiltration of inflammatory cells such as lymphocytes and macrophages. Mechanisms of onset of chronic rheumatoid arthritis have been reported to be based on such factors as heredity, bacterial infection and the contribution of various cytokines and growth factors, but the overall mechanism of onset has remained unclear. In recent years, cytokines and growth factors including interleukin-1 (IL-1), interleukin-8 (IL-8), tumor necrosis factor.alpha. (TNF.alpha.), transforming growth factor.beta. (TGF.beta.), fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) have been detected in the synovial membrane and synovial fluid of chronic rheumatoid arthritis patients (Nouri et al., Clin. Exp. Immunol. 55:295-302, 1984; Thornton et al., Clin. Exp. Immunol. 86:79-86, 1991; Saxne, et al., Arthritis Rheum. 31:1041-1045, 1988; Seitz et al., J. Clin. Invest. 87:463-469, 1991; Lafyatis et al., J. Immunol. 143:1142-1148, 1989; Melnyk et al., Arthritis Rheum. 33:493500, 1990). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Diagnostic and therapeutic agents for rheumatoid arthritis Inventor(s): Sato, Koichiro; (Fukushima-shi, JP), Homma, Yoshimi; (Fukushima-shi, JP) Correspondence: FITZPATRICK CELLA HARPER & SCINTO; 30 ROCKEFELLER PLAZA; NEW YORK; NY; 10112; US Patent Application Number: 20030152572 Date filed: October 4, 2002 Abstract: The present invention provides a therapeutic agent for rheumatoid arthritis which inhibits the growth of synoviocytes mediated by c-erbB-2 by clarifying the participation of c-erbB-2 in the growth of synoviocytes in rheumatoid arthritis patients and inhibiting the activation or expression of c-erbB-2. Excerpt(s): The present invention relates to diagnostic and therapeutic agents for rheumatoid arthritis which inhibit the growth of synoviocytes mediated by c-erbB-2, and a diagnostic method for rheumatoid arthritis which comprises detecting c-erbB-2. Rheumatoid arthritis is a systematic, chronic inflammatory disease characterized by the growth of synoviocytes at joints and the abnormality of immunoreaction, which gradually leads to the collapse of tendon, cartilage and bone tissues [Ann. Rheum. Dis., 52, S39-S47 (1993)]. So far, little has been elucidated about the signal transduction for excessive growth of synoviocytes in rheumatoid arthritis; however, the participation of growth factors such as EGF (epidermal growth factor), PDGF (platelet-derived growth factor) and FGF (fibroblast growth factor) which are present in synovia has been suggested [The Journal of Orthopaedic Science, 67, 859-865 (1993), Semin. Arthritis Rheum., 21, 191-199 (1991)]. There are also reports on the elevated expression levels of PDGF receptor in synoviocytes [Scand. J. Immnol., 27, 285-294 (1988)] and FGF receptor in focal T cells [Arthritis Rheum., 39, 914-922 (1996)]. However, little has been reported
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about EGF receptor (hereinafter referred to as EGFR) in tissues affected by rheumatoid arthritis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
EP4 receptor inhibitors to treat rheumatoid arthritis Inventor(s): Shimojo, Masato; (Chita-gun, JP), Okumura, Takako; (Chita-gun, JP), Audoly, Laurent; (Groton, CT) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020077329 Date filed: October 15, 2001 Abstract: The invention features a method of treating rheumatoid arthritis in a mammal comprising administering an agent that inhibits prostaglandin EP4 receptor (EP4) activity. Also featured is a method of identifying agents that selectively inhibit EP4 activity in vivo. Excerpt(s): This application claims priority, under 35 U.S.C.sctn.119(e), from U.S. provisional application No. 60/241,825 filed Oct. 19, 2000. The present invention features methods of treating rheumatoid arthritis by administering an agent that inhibits prostaglandin EP4 receptor activity. The invention also includes methods of identifying agents that selectively inhibit prostaglandin EP4 receptor activity in vivo. Prostaglandin E.sub.2 (PGE.sub.2) is a potent modulator involved in the pathogenesis of arthritis. PGE.sub.2 binds to at least four subtypes of PGE receptor, designated EP1, EP2, EP3, and EP4. Molecular studies have revealed that all subtypes are 7-transmembrane spanning receptors that belong to the G-protein coupled receptor superfamily (Robert et al., Am. Soc. Pharm. Exp. Ther. 46: 205-29, 1994). EP1 activation stimulates the release of intracellular calcium via a G protein-mediated mechanism; EP2 and EP4 both activate adenylate cyclase via stimulatory G proteins, but differ in their response to certain ligands; and EP3 inhibits adenylate cyclase via inhibitory G-proteins (Robert et al., supra, Negishi et al., Biochimica Biophys. Acta 1259:109-20, 1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human T Cell Clone Specific for Rheumatoid Arthritis Inventor(s): Tsuruta, YUJI; (osaka, JP), Takemoto, Hiroshi; (Hyogo, JP), Suzuki, Ryuji; (Nara, JP), Toyosaki-Maeda, Tomoko; (Hyogo, JP) Correspondence: Foley & Lardner; Washington Harbour; 3000 K Street NW Suite 500; PO Box 25696; Washington; DC; 20007-8696; US Patent Application Number: 20020076725 Date filed: September 14, 1998 Abstract: A human T cell clone recognizing an antigen expressed by a synovial cell of a rheumatoid arthritis (RA) patient in HLA-DR-restricted manner is disclosed, which clone is very useful in exploring the pathogenesis of RA and developing a method for treating and preventing RA. Excerpt(s): The present invention relates to an agent useful in diagnosing, preventing and/or treating an autoimmune disease, and particularly, to a T cell clone which is specifically reactive to an antigen presented on a certain HLA-DR which is expressed by
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a synovial cell of a patient suffering from rheumatoid arthritis (RA). An immune response, which is primarily a reaction to destroy and eliminate exogenous material invading from external ambient, is usually induced specifically for a non-self molecule (antigen). However, when the recognizability between a self and a non-self molecule is disordered by some reasons (failure in self tolerance), various autoimmune diseases develop, such as systemic erythematodes, pachydermia, multiple sclerosis (MS), rheumatoid arthritis (termed as RA, hereinafter), and the like. RA frequently attacks women after middle-age. Predominant symptoms of RA include the swelling and deformation, pain, and motor function failure in joints, and its histopathological finding is an abnormal outgrowth of synovial tissues lining capsula articularis joint capsule). At the outgrowing tissues, a large number of immunocompetent cells (neutrophile, macrophage, lymphocyte), as well as a folicle formation of B cells, which are responsible for antibody production, and a population of helper T cells, are observed. Previous epidemiologic survey has shown that RA is associated with HLA-DRB1 allele as a disease-sensitive gene, and that RA frequently attacks women at pre- and postmenopausal period. Pathologically, the infiltration of memory type CD4-positive, CD45RO-positive T cells into lesions (synovial tissue) has been found, suggesting that the helper T cells having a memory for a certain antigen would be highly responsible for the onset of RA. Nowadays, although non-steroidal anti-inflammatory agents, immunomodulators, and steroid agents are predominately utilized in the therapy for RA, these medicaments may produce various side effects (gastrointestinal injury, nephropathy, and the like). Additional disadvantages in the usage of immunomodulators include the delayed exertion of effect, and besides a possible ineffectiveness due to its repetitive administration, and therefore, the usage of immunomodulators is questionable. Recently, it is begining that immunosuppressants are used in order to control more efficiently the inflammation. Unfortunately, imuunosuppressants may produce severe side effects such as myelopathy, and therefore, there is a large demand of the exploration for a treatment targeting the lesion. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Isolated Nucleotide Sequences Associated with Multiple Sclerosis or Rheumatoid Arthritis and a Process of Detecting Inventor(s): Perron, Herve; (Lyon, Fr), Beseme, Frederic; (Villefontaine, Fr), Bedin, Frederic; (Lyon, Fr), Jolivet-Reynaud, Colette; (Bron, Fr), Tuke, Philip William; (London, Gb), Komurian-Pradel, Florence; (Saint Cyr Au Mont D'or, Fr), Garson, Jeremy Alexander; (Guildford, Gb), Paranhos-Baccala, Glaucia; (Lyon, Fr), Mandrand, Bernard; (Villeurbanne, Fr) Correspondence: Oliff & Berridge, PLC; P.O. Box 19928; Alexandria; VA; 22320; us Patent Application Number: 20030039664 Date filed: November 26, 1997 Abstract: The invention provides viral material and nucleotide fragments associated with multiple sclerosis and/or rheumatoid arthritis for use in methods of diagnosis, prophylaxis, and therapy. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 08/756,429, filed Nov. 26, 1996. Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), the cause of which remains as yet unknown. "Multiple sclerosis (MS) is the most common neurological disease of young adults with a prevalence in Europe and North America of between 20 and 200 per 100,000. It is
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characterized clinically by a relapsing/remitting or chronic progressive course, frequently leading to severe disability. Current knowledge suggests that MS is associated with autoimmunity, that genetic background has an important influence and that "infectious" agent(s) may be involved. Indeed, many viruses have been proposed as possible candidates but as yet, none of them has been shown to play an aetiological role. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for Tratment of Non-Rheumatoid Arthritis Inventor(s): Macias, William Louis; (Indianapolis, IN) Correspondence: Eli Lilly and Company; Patent Division; P.O. Box 6288; Indianapolis; IN; 46206-6288; US Patent Application Number: 20030119860 Date filed: February 24, 2000 Abstract: A method is disclosed for the treatment of non-rheumatoid arthritis by administering to a mammal in need thereof a therapeutically effective amount of an sPLA 2 inhibitor. Excerpt(s): The present invention is directed to a method for treating non-rheumatoid arthritis. More specifically, the present invention is directed to a method for treating the causes and/or the symptoms of various forms of non-rheumatoid arthritis in mammals by administering a therapeutically effective amount of an sPLA.sub.2 inhibitor. "Arthritis" is the name given to disease states encompassing many different conditions frequently having entirely different symptoms, causes, and known treatments. Although, the word "arthritis" means joint inflammation, it has come to encompass disorders that affect not only the joints but other connective tissue of the body including supporting structures such as muscles, tendons, and ligaments as well as the protective coverings of internal organs. Some of the most commonly occurring forms of arthritis are osteoarthritis, ankylosing spondylitis, rheumatic fever, and gout. Some forms of inflammatory arthritis are characterized by lymphokine-mediated inflammation of the joints. The use of selected secretory phospholiase A2 (sPLA.sub.2) inhibitors to treat rheumatoid arthritis is described in European Patent No. 0675110 (published Oct. 4, 1995) and in U.S. Pat. No. 5,654,326. The most common form of non-rheumatoid arthritis is osteoarthritis, a degenerative joint disease which primarily affects cartilage that covers and cushions the ends of the bones causing it to fray, wear, ulcerate, and in extreme cases, to disappear entirely leaving a bone on bone joint. The disease can result in severe disability particularly in the weight bearing joints such as the knees, hips, and spine. Osteoarthritis is distinguishable, for example, from rheumatoid arthritis in that osteoarthritis involves little or no inflammation and is confined to the joints and surrounding tissue where there is a breakdown or disintegration of cartilage and other tissue thereby making it difficult for the joints to operate properly. The occurrence of osteoarthritis frequently increases with advancing years. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for treating rheumatoid arthritis using IL-17 antagonists Inventor(s): Mohler, Kendall M. (Poulsbo, WA) Correspondence: Immunex Corporation; Law Department; 51 University Street; Seattle; WA; 98101 Patent Application Number: 20020136724 Date filed: October 18, 2001 Abstract: A method of treating a mammal afflicted with rheumatoid arthritis comprising administering a soluble form of IL-17 receptor is disclosed. Excerpt(s): This application claims the benefit under U.S.C. 119(e) of U.S. provisional application serial number 60/241,230, filed Oct. 18, 2000. All of which is incorporated by reference herein. The invention pertains to methods for treating certain diseases and disorders associated with inflammatory and immunoregulatory responses. More particularly, the present invention involves treating rheumatoid arthritis by administering an IL-17 inhibitor or IL-17 antagonist, in particular IL-17 receptor, to an individual afflicted with such rheumatoid arthritis. Cytokines are hormone-like molecules that regulate various aspects of an immune or inflammatory response. Cytokines exert their effects by specifically binding receptors present on cells, and transducing a signal to the cells. Rouvier et al. (J. Immunol. 150:5445; 1993) reported a novel cDNA which they termed CTLA-8; cloning of the human homolog led to the identification of this family of molecules as Interleukin-17 (IL-17; Yao et al., Immunity 3:811; 1995). IL-17 is a cytokine produced by activated T cells that stimulates the secretion of various proinflammatory molecules, including tumor necrosis factor.alpha. (TNF-.alpha.), Interleukin-1.beta. (IL-1.beta.) and prostaglandin E.sub.2 (PGE.sub.2) from macrophages (Jovanovic et al., J. Immunol. 160:3513; 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for treatment of rheumatoid arthritis Inventor(s): Whitehead, Clark M. (Warminster, PA), Earle, Keith A. (North Wales, PA), Alila, Hector W. (North Wales, PA), Thompson, W. Joseph; (Doylestown, PA) Correspondence: Robert Stevenson; 702 Electronic Dr. Horsham; PA; 19044; US Patent Application Number: 20030176316 Date filed: October 23, 2002 Abstract: Substituted condensation products of N-benzyl-3-indenylacetamides with heterocyclic aldehydes and other such inhibitors are useful for the treatment of rheumatoid arthritis. Excerpt(s): This invention relates to the treatment of rheumatoid arthritis. Scientists estimate about 2.1 million people, or 1 percent of the U.S. adult population, have rheumatoid arthritis. By any reasonable measure, the financial and social, and personal impact of all types of arthritis, including rheumatoid arthritis, is substantial. From an economic standpoint, the medical and surgical treatment for rheumatoid arthritis and the wages lost because of disability caused by the disease add up to millions of dollars. Daily joint pain is an inevitable consequence of the disease, and most patients also experience some degree of depression, anxiety, and feelings of helplessness. In some cases, rheumatoid arthritis can interfere with a person's ability to carry out normal daily activities, limit job opportunities, or disrupt the joys and responsibilities of family life.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mouse model for rheumatoid arthritis Inventor(s): Faustman, Denise L. (Weston, MA), Hayashi, Takuma; (Malden, MA) Correspondence: Leon R Yankwich; Yankwich & Associates; 201 Broadway; Cambridge; MA; 02139; US Patent Application Number: 20030005469 Date filed: July 16, 2002 Abstract: Nonobese Diabetic Mice (NOD mice) that do not develop diabetes may be bred to produce F.sub.1 offspring that develop a condition that closely mimics rheumatoid arthritis (RA) in humans. The RA-like disease in the F.sub.1 mice, designated NOD-RA mice, is similar to human RA in clinical, radiological, histological and serological characteristics. The parents (F.sub.0) and their progeny (F.sub.1) are not diabetic and never develop hyperglycemia, and the parental mice (F.sub.0) do not themselves exhibit any symptoms of the RA-like condition that afflicts some of their progeny. The incidence, penetrance, gender domination, progression, and lifelong exacerbation of symptoms after pregnancy shown in the RA-like condition afflicting NOD-RA mice are all comparable to phenomena observed in the human disease. The NOD-RA mice provide a new spontaneous model of human RA that will be useful for studying rheumatoid arthristis and testing new drugs and reagents for treating or diagnosing the disease. Excerpt(s): The present invention pertains to the field of medical research, particularly to the development of mammalian models of human rheumatoid arthritis. Rheumatoid arthritis (RA) is a common autoimmune disease characterized by joint swelling, deformation and, ultimately, destruction, culminating in severe physical disability. De Graaf et al., in The Epidemiolog of Chronic Rheumatism, Dellgren and Ball, eds. (Blackwell, Oxford, 1963), pp. 446-56; Meenam et al., Arthritis Rheum., 24:544-50 (1981); Gabriel et al., J. Rheumatol, 26:1269-74 (1999); James, Clin Exp. Rheumatol, 17:392-93 (1999). RA is a progressive condition with well-recognized symptoms including symmetrical peripheral joint swelling and synovial inflammation while sparing the axial skeleton; the presence of rheumatoid factor (RF) autoantibodies; increased concentrations of interleukin-6 (IL-6), interleukin-1.beta. (IL-1.beta.), and granulocyte/macrophage colony-stimulating factor (GM-CSF) in serum and synovial fluid; low concentrations of interleukin-ra (IL-ra); and pregnancy-induced disease remission followed by severe postpartum flares, that is, while women with RA commonly undergo remission during pregnancy, the disease returns and may be even more severe and show a new onset or more accelerated course after delivery. See, Turgen, in Immunology and Serology in Laboratory Medicine. 2.sup.nd edition, Shanahan ed. (Mosby Year Book, St. Louis, 1996), pp. 387-98; Hirano et al., Eur. J. Immunol, 18:1797-1801 (1988); Wilder et al., Ann. N. Y. Acad. Sci., 876:14-31 (1999); Iijima et al., J. Rheumatol, 26:755-56 (1999); Ostensen, Ann. N.Y Acad. Sci., 876:13143 (1999). In medical research directed to understanding, diagnosing and treating RA, several animal models of the disease have been described, but no spontaneous animal model that closely mimics all the features of the human disease has been discovered (See, for example, Hang et al., 1982. J. Exp. Med., 155:1690-1701; and Kouskoff et al., 1996. Cell, 87:811-822). Kouskoffet al. report a RA mouse model that exhibits aggressive arthritis, produced by mating a T cell receptor (TCR) transgenic mouse strain with a NOD strain. This RA mouse model is strictly dependent on the presence of the KRN
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transgene and is characterized by several inherent symptomological features of RA that distinguish it from human RA (hRA), however, including: 100% penetrance, early (i.e., 25-35 days) onset of disease, attack of the distal interphalangeal joints, inflammation of the spine, large excess of myeloid cells over T lymphocytes and plasma cells in the synovial membrane, a total absence of rheumatoid factor (RF) autoantibodies, and a coating of IgG deposits on internal organs. These features result in a more aggressive RA than the RA typically found in humans. Human RA has preferential disease expression in middle-aged females, peripheral disease sparing of the DIP joints, rheumatoid factor autoantibodies, similar peripheral and joint cytokine derangements, etc. The mechanism of development of arhritis-like disease in NOD/TCR mice differs dramatically from that of natural RA expression in humans, limiting the utility of this RA mouse as a model for hRA. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
PEPTIDE DERIVED FROM AN ANTIGEN RECOGNIZED BY AUTOANTIBODIES FROM PATIENTS WITH RHEUMATOID ARTHRITIS, ANTIBODY DIRECTED AGAINST SAID PEPTIDE, A COMBINATORIAL ANTIGEN, AND A METHOD OF DETECTING AUTO- IMMUNE ANTIBODIES Inventor(s): HOET, RENE MICHAEL A; (NIJMEGEN, NL), VAN VENROOIJ, WALTHERUS JACOBUS W; (NIJMEGEN, NL), RAATS, JOZEF MARIA HENDRIK; (NIJMEGEN, NL) Correspondence: PEACOCK MYERS AND ADAMS P C; P O BOX 26927; ALBUQUERQUE; NM; 871256927 Patent Application Number: 20020137092 Date filed: September 30, 1999 Abstract: The invention relates to a peptide derived from an antigen recognized by autoantibodies, which peptide is reactive with autoimmune antibodies from a patient suffering from rheumatoid arthritis. The peptide according to the invention possesses a modified arginine residue. The invention also relates to antibodies against the peptide and a method of detecting autoimmune antibodies. Excerpt(s): The present invention relates to a peptide derived from an antigen recognized by autoantibodies from patients with rheumatoid arthritis, which peptide is reactive with autoimmune antibodies from a patient suffering from rheumatoid arthritis. Such a peptide is known from the European patent application 0 511 116 (Clonatec S. A.). This application describes an antigen comprising a filaggrin or profilaggrin fragment. The peptide is recognized by rheumatoid arthritis-specific autoimmune antibodies. Rheumatoid arthritis (RA) is a systemic autoimmune disease. It is the most commonly occurring inflammatory disease of the joints, it is chronic and may lead to severe physical disablement. The object of the present is to provide a peptide which is reactive with autoimmune antibodies from a patient suffering from rheumatoid arthritis, which peptide is suitable for diagnostic research with increased specificity while also being useful for other purposes such as obtaining (raising, selecting and isolating) poly- and monoclonal antibodies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Peptides designed for the diagnosis and treatment of rheumatoid arthritis Inventor(s): Moereels, Henri; (Ekeren, BE), Union, Ann; (Aalter, BE), Meheus, Lydie; (Merelbeke, BE) Correspondence: Patricia A. Kammerer; Howrey Simon Arnold & White, LLP; 750 Bering Drive; Houston; TX; 77057-2198; US Patent Application Number: 20020143143 Date filed: December 21, 2000 Abstract: The present invention relates to peptides that mimic the immunogenic determinants of self-proteins recognized by autoimmune antibodies in a biological sample from patients suffering from rheumatoid arthritis (RA). More particularly, the present invention relates to citrulline-containing peptides, which react with the majority of the latter antibodies. Furthermore, the present invention relates to diagnostic tools for a more convenient and sensitive diagnosis of RA and to therapeutic methods to treat RA. Excerpt(s): The present invention relates to peptides that mimic the immunogenic determinants of self-proteins recognised by autoimmune antibodies in a biological sample from patients suffering from rheumatoid arthritis (RA). More particularly, the present invention relates to citrulline-containing peptides, which react with the majority of the latter antibodies. Furthermore, the present invention relates to diagnostic tools for a more convenient and sensitive diagnosis of RA and to therapeutic methods to treat RA. Rheumatoid arthritis is a major crippling joint disease, which is systemic in nature and of unknown etiology. It affects 1% of the population, with a male to female ratio of 2:3. In terms of morbidity, the most important feature of RA is joint erosion which leads to pain, deformity and in some cases, severe disability. Life expectations in patients with a severe form of the disease are reduced by up to 10 years. RA has all the features of an autoimmune disease, including the presence of a variety of autoantibodies in patients' sera and the capacity to induce illness by transfer of pathogenic T cells in animal models. The classification of the disease can be challenged on the grounds that borderline forms are very common; furthermore inflammation of the joints is not only restricted to RA, but occurs also in other non-autoimmune diseases such as osteoarthritis, reactive arthritis and gout. The diagnosis of rheumatoid arthritis is initially based on clinical manifestations. As an early diagnosis allows an adjusted treatment, which can highly improve life quality of the patients, it is of major importance for rheumatologists to have reliable diagnostic criteria at their disposal. Serological support for diagnosing RA is not very well established and is based mainly on the presence of rheumatoid factors (RF). However, a substantial number of RA patients are RF-negative, while on the other hand, RF is also present in other rheumatic diseases including Sjogren's syndrome and systemic lupus erythematosus, in some chronic bacterial and acute viral infections, in certain parasitic diseases and chronic inflammatory diseases, and has furthermore been demonstrated in sera from healthy persons. The rather low specificity of RF thus necessitates additional testing for a second RA-specific antibody. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pipecolic acid derivatives of proline threonine amides useful for the treatment of rheumatoid arthritis Inventor(s): Hanson, Gunnar J. (Skokie, IL) Correspondence: J. Timothy Keane; PHARMACIA CORPORATION; Corporate Patent Department; P.O. Box 5110; Chicago; IL; 60680; US Patent Application Number: 20010027247 Date filed: February 26, 2001 Abstract: Non-peptidic compounds characterized by containing a segment condensed from pipecolic acid, aspartic acid, proline and threonine, or derivatives thereof, are useful to treat autoimmune diseases and inflammatory conditions. Compounds of particular interest are those of the formula: 1wherein R.sup.1 is phenyl or cyclohexyl; wherein R.sup.2 is hydrido or methyl; wherein R.sup.3 is selected from hydrido, hydroxy, acetylamino, acetyl(Lys/Tyr/Thr)NH--, propionylamino and benzyloxycarbonylamino; wherein R.sup.5 is selected from isopropyl, isobutyl, npropyl, n-butyl, aminopropyl, aminobutyl, phenyl, benzyl, hydroxyphenyl, hydroxybenzyl, morpholinocarbonylethyl, morpholinocarbonylpropyl, piperazinocarbonylethyl, piperazinocarbonylpropyl, pyridinylcarbonylethyl, pyridinylcarbonylpropyl, oxazolylcarbonylethyl, oxazolylcarbonylpropyl, azepinylcarbonylethyl and azepinylcarbonylethyl; wherein R.sup.6 is selected from hydrido, methyl, hydroxy, methoxy, phenyl and aminocarbonyl; wherein R.sup.7 is carboxyl or methylthiomethyl; wherein R.sup.9 is selected from hydrido, hydroxy, methoxy and phenyl; wherein R.sup.12 is selected from methyl, ethyl, propyl, butyl, isobutyl, --CH(iBu)CH.sub.2OH and --CH(iBu)CONH.sub.2; or a pharmaceuticallyacceptable amide, ester or salt thereof. A disease state of particular interest for use of the compounds would be rheumatoid arthritis. Excerpt(s): Non-peptidic compounds are described for treatment of autoimmune diseases. Of particular interest are pipecolic acid derivatives compounds incorporating a characterizing segment condensed from pipecolic acid, aspartic acid, proline and threonine, or derivatives thereof, which compounds are useful to treat rheumatoid arthritis. Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovium. This disease is triggered by an immune response generated via the molecular recognition of the T-cell receptor on CD4-positive T cells with a complex of disease-inducing peptides bound to Human Leukocyte Antigen (HLA) class II molecules. Rheumatoid arthritis (RA) is associated with the expression of certain HLA class II molecules, particularly the DR4-dw4, as well as DR1 and DR4dw14. It is known that blockade of the interaction between a given class II molecule, peptide ligand, and T cell receptor inhibits specific T cell responses both in vitro and in vivo. It is further known that blockade of the above interaction in animal models of autoimmunity prevents or ameliorates autoimmune disease. Inhibitor compounds which block the binding of disease-inducing peptides to an RA-associated HLA molecule, but which will not interfere with a patient's ability to generate other class IIrestricted immune responses, constitutes a selective immunosuppressive anti-RA therapy. Compounds which compete with disease-inducing endogenous peptides for binding to RA-associated HLA molecules and may thereby inhibit disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Polynucleotides and polypeptides associated with the development of rheumatoid arthritis Inventor(s): Carman, Julie; (Lawrenceville, NJ), Lu, Pin; (Princeton Jct., NJ), Bowen, Michael; (Rockville, MD), Nadler, Steven G. (Princeton, NJ), Neubauer, Michael G. (Skillman, NJ) Correspondence: STEPHEN B. DAVIS; BRISTOL-MYERS SQUIBB COMPANY; PATENT DEPARTMENT; P O BOX 4000; PRINCETON; NJ; 08543-4000; US Patent Application Number: 20030170742 Date filed: December 3, 2002 Abstract: The present invention is directed to polynucleotides encoding polypeptides associated with the development of rheumatoid arthritis and homologs thereof. The invention further relates to diagnostic and therapeutic methods for utilizing these polynucleotides and polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention, and compounds identified thereby. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/337,429, filed Dec. 3, 2001, and hereby expressly incorporated by reference in its entirety. The present invention provides polynucleotides encoding polypeptides associated with the development and progression of rheumatoid arthritis and homologs thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for utilizing these polypeptides in the diagnosis, treatment, and/or prevention of rheumatoid arthritis and related disease states. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction. Initial destruction of cartilage and bone is associated with the formation of a pannus, consisting of a hypertrophic synovial membrane containing hyperplastic synoviocytes and an infiltrate of inflammatory cells including T cells, B cells, CD68+macrophages, mast cells, and endothelial cells. The causes of RA are not well understood. Genetic studies have linked expression of specific major histocompatibility complex class II antigens to the development of RA, suggesting the involvement of antigen-specific mechanisms in disease progression (Zanelli et al., Hum. Immunol. 61:1254-1261 (2000)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for production of bee venom as pharmaceutical product which can be used effectively in the treatment of rheumatoid arthritis and viral diseases Inventor(s): Abbadi, Ali Salem El; (Giza, EG) Correspondence: NATH & ASSOCIATES; 1030 15th STREET; 6TH FLOOR; WASHINGTON; DC; 20005; US Patent Application Number: 20030118597 Date filed: October 11, 2002 Abstract: The traditional treatment for Rheumatoid Arthritis relies on a course of synthetic drugs, which range from the use of gold salts to anti-inflammatory drugs
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including both steroids and non-steroids. These drugs specially the steroids can affect adrenal and pituitary glands & cause impotence, edema, poor wound healing, reduce neurological response and cardiac irregularities.VACSERA began the first clinical studies with bee venom therapy and proved its efficiency for treatment of variety of diseases such as Rheumatoid arthritis and viral infections especially (HCV). Bee Venom was separated by a scientific method and then we determine the dosage form, toxicity, bioavailability, teratogenicity, (anti-teratogenic effect), safety and treatment schedule.The use of Bee venom in treatment of arthritis has been proved to be beneficial to many patients, primarily due to the presence of a number of polypeptides, peptides, enzymes and amines. The venom is administered according to the enclosed leaflet and physician instructions in doses which vary according to the disease and its severity. Excerpt(s): The invention relates to the adaptability of the traditional medicine (Bee venom) for treatment of a lot of diseases such as rheumatoid arthritis and viral diseases specially (HCV) in a pharmaceutical form and presents a noble service for many patients. Ancient Egyptians and Babilians were innovators; they used the Bee stings to relief pain accompanying Rheumatism and osteoarthritis since 2000 years B.C. Chinese have started the bee venom therapy since 1530 In the nineteenth century (1935) French. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
RHEUMATOID ARTHRITIS REMEDY CONTAINING ANTI-IL-8 ANTIBODY AS ACTIVE INGREDIENT Inventor(s): MATSUSHIMA, KOUJI; (CHIBA, JP), AKAHOSHI, TOHRU; (TOKYO, JP) Correspondence: KATE H MURASHIGE; MORRISON & FOERSTER; 2000 PENNSYLVANIA AVENUE NW; SUITE 5500; WASHINGTON; DC; 200061888 Patent Application Number: 20010006637 Date filed: October 19, 1998 Abstract: A therapeutic agent for rheumatoid arthritis comprising anti-IL-8 antibody as an active ingredient. Excerpt(s): The present invention relates to a therapeutic agent for treating rheumatoid arthritis comprising anti-interleukin-8 (IL-8) antibody as an active ingredient. IL-8 is a protein that belongs to the C--X--C chemokine subfamily and was formerly designated as the monocyte-derived neutrophil chemotactic factor, the neutrophil attractant/activation protein-1, the neutrophil activating factor and the like. IL-8 is a factor that activates neutrophils and provides them with migratory ability, and is produced by a variety of cells in the presence of inflammatory cytokines such as IL1.beta., TNF.alpha., etc. (Koch, A. E. et al., J. Investig. Med. (1995) 43, 28-38; Larsen, C. G. et al., Immunology (1989) 68, 31-36), mitogens such as PMA, LPS etc. (Yoshimura, T. et al, Proc. Natl. Acad. Sci. U.S.A. (1987) 84, 9233-9237), and heavy metals such as cadmium etc. (Horiguchi, H. et al., Lymphokine Cytokine Res. (1993) 12, 421-428). It was reported that monocytes isolated from the synovial fluid of patients with rheumatoid arthritis had the elevated levels of expression of chemokines such as IL-8, GRO, MCAF, MIP-1.alpha., MIP-1.beta. and the like as compared to the monocytes isolated from the peripheral blood of healthy subjects or patients with rheumatoid arthritis (Hosaka, S. et al., Clin. Exp. Immunol. (1994) 97, 451-457). It is believed that overexpression of those various cytokines promotes migration of inflammatory cells to the joints, but it is not known which chemokine plays a central role in the pathogenesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of CD25 binding molecules in the treatment of rheumatoid arthritis or skin diseases Inventor(s): Schreier, Karin; (Basel, CH), Schreier, Max H. (Basel, CH), Amlot, Peter Lloyd; (London, GB) Correspondence: THOMAS HOXIE; NOVARTIS CORPORATION; PATENT AND TRADEMARK DEPT; 564 MORRIS AVENUE; SUMMIT; NJ; 079011027 Patent Application Number: 20020110558 Date filed: January 25, 2001 Abstract: Use of a CD25 binding molecule which comprises at least one antigen binding site comprising at least one domain which comprises in sequence, the hypervariable regions CDR1, CDR2 and CDR3; said CDR1 having the amino acid sequence Arg-TyrTrp-Met-His, said CDR2 having the amino acid sequence Ala-Ile-Tyr-Pro-Gly-Asn-SerAsp-Thr-Ser-Tyr-Asn-Gln-Lys-Phe-Glu-- Gly, and said CDR3 having the amino acid sequence Asp-Tyr-Gly-Tyr-Tyr-Phe-- Asp-Phe, in the treatment of rheumatoid arthritis or inflammatory or hyperproliferative skin diseases. Excerpt(s): The invention is directed to the use of a CD25 binding molecule in the treatment of rheumatoid arthritis or inflammatory and hyperproliferative skin diseases. More specifically the present invention provides in a first aspect the use of a CD25 binding molecule which comprises at least one antigen binding site comprising at least one domain which comprises in sequence, the hypervariable regions CDR1, CDR2 and CDR3; said CDR1 having the amino acid sequence Arg-Tyr-Trp-Met-His, said CDR2 having the amino acid sequence Ala-lle-Tyr-Pro-Gly-Asn-Ser-Asp-Thr-Ser-Tyr-Asn-GlnLys-Phe-Glu-- Gly, and said CDR3 having the amino acid sequence Asp-Tyr-Gly-TyrTyr-Phe-- Asp-Phe; or direct equivalents thereof in the treatment of rheumatoid arthritis or inflammatory or hyperproliferative skin diseases. Treatment of rheumatoid arthritis includes control or amelioration of the disease and/or its sequellae, e.g. symptoms, such as number of tender and swollen joints, degree of tenderness and swelling, or pain, as well as control or amelioration of aetiological components. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of inhibitors of the activation of CXCR4 receptor by SDF-1 in treating rheumatoid arthritis Inventor(s): Winchester, Robert J. (New York, NY), Seki, Tetsunori; (Roosevelt Island, NY), Gulko, Percio Saltz; (Riverdale, NY) Correspondence: Cooper & Dunham LLP; 1185 Avenue of the Americas; New York; NY; 10036; US Patent Application Number: 20020039993 Date filed: January 31, 2001 Abstract: This invention provides a method for treating rheumatoid arthritis or other forms of inflammatory arthritis which comprises administering to a subject an amount of an agent effective to inhibit the activation of the CXCR4 receptor by SDF-1. This invention further provides a composition for treating rheumatoid arthritis comprising an effective amount of an agent capable of inhibiting the activation of the CXCR4 receptor by SDF-1 and a pharmaceutically acceptable carrier. This invention also provides a method for determining whether an agent is capable of inhibiting the
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activation of the CXCR4 receptor by SDF-1 comprising: (a) contacting cells expressing the CXCR4 receptor in the presence of SDF-1 with the agent under condition permitting activation of the CXCR4 receptor by SDF-1 if the agent is absent; and (b) determining whether the amount of activation of the CXCR4 receptor by SDF-1 is decreased in the presence of the agent relative to the amount of activation in its absence, such a decrease indicating that the agent is capable of inhibiting the activation of the CXCR4 receptor by SDF-1. Finally, this invention provides agents identified by such a method. Excerpt(s): This application claims priority of U.S. Ser. No. 09/127,651, filed Jul. 31, 1998, the content of which is hereby incorporated by reference. Throughout this application various references are referred to by arabic numbers within parenthesis. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. The architecture, cellular composition and state of cellular activation of the synovial membrane in rheumatoid arthritis have been well described(1,2), but fundamental questions still remain unanswered regarding the precise molecular nature and biologic significance of these inflammatory changes. The intimal synovial lining layer that is extensively altered in synovitis synovium through hyperplasia and infiltration is formed by the interaction of two distinct cell types: intimal synoviocytes derived from the fibroblastoid lineage and intercalated, hemopoietically-derived, monocytoid lineage cells(3-5). During histogenesis of the normal joint the lining cell apparently provides both guidance clues and receptor interactions to the specialized synovial monocytoid cells that result in its incorporation into the lining layer(1). Together, the cells comprising the intimal layer carry out a number of functions responsible for the integrity and sustenance of the joint. The form and function of the intimal synoviocyte apparently distinguishes them from fibroblastoid cells found deeper in the synovium, although relatively little is known about the differences between these members of the fibroblastoid lineage(6). Several genes have been identified that are selectively expressed in the normal intimal, but not subintimal synoviocytes including vascular cell adhesion molecule 1 (VCAM-1)(7), uridine diphosphoglucose dehydrogenase (UDPGD) and decay accelerating factor (DAF)(6). In chronic synovitis immunopathologic studies have shown that the fibroblastoid intimal synoviocytes respond to the events by proliferating and altering their pattern of gene expression to include expression of a variety of molecules that range from MHC class II structures, through cytokines to enzymes that directly participate in the destructive remodelling of joint tissues (1,8-13). In parallel, some of the fibroblasts in subintimal locations similarly express MHC class II and VCAM-1(6,13). However, the performance of more analytic studies of synoviocyte cell biology has been constrained because there is no basement membrane that delimits intimal synoviocytes from the subintimal fibroblastoid cells in either normal or inflamed joint tissues, and the purification and separate culture of these two potentially distinct lineages has been difficult, if not impossible. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with rheumatoid arthritis, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “rheumatoid arthritis” (or
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synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on rheumatoid arthritis. You can also use this procedure to view pending patent applications concerning rheumatoid arthritis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON RHEUMATOID ARTHRITIS Overview This chapter provides bibliographic book references relating to rheumatoid arthritis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on rheumatoid arthritis include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on rheumatoid arthritis: •
Rheumatoid Arthritis: Caring for Your Hands Source: Bethesda, MD: American Occupational Therapy Association, Inc. 1995. 40 p. Contact: American Occupational Therapy Association, 4720 Montgomery Lane, P.O. Box 31220, Bethesda, MD 20824-1220. (301) 652-2682. (800) 377-8555 ( TDD ). (301) 652-7711 (fax). Summary: This book for individuals with rheumatoid arthritis (RA) provides information for minimizing joint inflammation and protecting joints from damage. Causes of pain in RA are identified, including inflammation and swelling, deterioration of cartilage, pressure on the bone, and tenosynovitis. Common causes of deformities in RA are discussed, including joint contracture , joint instability, and tenosynovitis. Specific hand deformities are described, their causes are explained, and steps that individuals can take to minimize these deformities are presented. Signs of inflammation
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are identified, including pain and morning stiffness. Techniques for managing pain and stiffness in hands are suggested. Guidelines are provided for protecting joints, relieving muscle tension, using splints, maintaining mobility, and fighting fatigue. A list of additional resources is also included. 4 references, 17 figures, and 1 table. •
Conquering Rheumatoid Arthritis: The Latest Breakthroughs and Treatments Source: Amherst, NY: Prometheus Books. 2001. 255 p. Contact: Available from Prometheus Books. 59 John Glenn Drive, NY 14228-2197. (716) 691-0133 or (800) 421-0351. Website: www.prometheusbooks.com. PRICE: $20.00. ISBN: 1573928860. Summary: This book for patients describes the origins, disease course, and treatment of rheumatoid arthritis (RA). Rheumatoid arthritis affects over two million Americans. It is three times more common in women than men and becomes increasingly common in people as they age. RA is an inflammatory disease of the synovium, or lining of a joint, that results in pain, stiffness, swelling, joint damage, and loss of function in the joints. Chapters discuss the body's immune system; the anatomy of the synovial joints; the system by which the body's immune system attacks these joints; the genetic origins of RA and gene therapy; stem cell research and therapy; traditional treatments for RA including NSAIDS, DMARDS, and steroids; new medications including etanercept, COX-1 and COX-2 enzymes, leflunomide, and infliximab; clinical trials; and potential therapies. Appendices include related websites and a glossary. 14 figures.
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Living With Rheumatoid Arthritis, Second Edition Source: Baltimore, MD: The Johns Hopkins University Press. 2003. 290 p. Contact: Johns Hopkins University Press. 2715 N. Charles St., Baltimore, MD 21218-4319. (410) 516-6934. Website: www.jhupbooks.com. Summary: This book seeks to educate patients with rheumatoid arthritis (RA) about their condition. The premise of this book is that the better the RA patient understands his or her condition, the better he or she can cope with the illness. The book is divided into six parts. Part one discusses RA and provides an overview of RA with chapters on joints, inflammation, disease course and prognosis, diagnostic tests, and other symptoms. Part two discusses coping with RA with chapters describing strategies for identifying problems, setting goals, and coping with fatigue, pain, and emotions. Part three discusses exercises and rehabilitation. Part four discusses traditional and current medications. Part five discusses other treatments for RA including alternative and complementary therapies, nutrition, and surgery. Part six discusses a range of topics including disability benefits, health insurance, financial matters, traveling, and other medical concerns. A glossary and bibliography are included. Numerous diagrams.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “rheumatoid arthritis” at online booksellers’ Web sites, you may
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discover non-medical books that use the generic term “rheumatoid arthritis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “rheumatoid arthritis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Comprehensive guide to new therapeutic approaches of methotrexate in rheumatoid arthritis; ISBN: 0919839096; http://www.amazon.com/exec/obidos/ASIN/0919839096/icongroupinterna
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A Workbook for Persons With Rheumatoid Arthritis; ISBN: 999738766X; http://www.amazon.com/exec/obidos/ASIN/999738766X/icongroupinterna
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Adults With Rheumatoid Arthritis: An Aota Practice Guideline by Y. Lynn Yasuda; ISBN: 1569001529; http://www.amazon.com/exec/obidos/ASIN/1569001529/icongroupinterna
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All about Bone, Joint, Muscle, and Arthritis Pain in Childhood: A Guide to Juvenile Rheumatoid Arthritis, Injuries, and Rheumatic Diseases for Parents and Professionals by Thomas J. A. Lehman (2004); ISBN: 0195157281; http://www.amazon.com/exec/obidos/ASIN/0195157281/icongroupinterna
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Anna's Story and New Effective Treatments for Rheumatoid Arthritis by Richard L. Lyonharte (1999); ISBN: 0741402041; http://www.amazon.com/exec/obidos/ASIN/0741402041/icongroupinterna
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Arthritis Sourcebook: Basic Consumer Health Information About Specific Forms of Arthrits and Related Disorders, Including Rheumatoid Arthritis, Osteoarthrits, Gout, polymya (Health Reference Series, Vol 46) by Allan R. Cook (Editor) (1998); ISBN: 0780802012; http://www.amazon.com/exec/obidos/ASIN/0780802012/icongroupinterna
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Arthritis: About Osteoarthritis and Rheumatoid Disease, Including Rheumatoid Arthritis by Anthony Di Fabio, Gus J. Prosch (1997); ISBN: 0961543736; http://www.amazon.com/exec/obidos/ASIN/0961543736/icongroupinterna
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Auranofin in Rheumatoid Arthritis by Norman L. Gottlieb (Editor) (1987); ISBN: 0941741001; http://www.amazon.com/exec/obidos/ASIN/0941741001/icongroupinterna
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Autoimmunity, Rheumatoid Arthritis and Cyclosporin A by Y. Mizushima (Editor), Amor (1991); ISBN: 1850703051; http://www.amazon.com/exec/obidos/ASIN/1850703051/icongroupinterna
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Challenges in Rheumatoid Arthritis by H. A. Bird (Editor), Michael L. Snaith (Editor); ISBN: 0632049391; http://www.amazon.com/exec/obidos/ASIN/0632049391/icongroupinterna
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Chronic Diseases in the Year 2005: Scenario on Rheumatoid Arthritis 1990-2005 Scenario Report Commissioned by the Steering Committee on Future Healt by H. Verkleij, A. F. Casparie (1995); ISBN: 0792333675; http://www.amazon.com/exec/obidos/ASIN/0792333675/icongroupinterna
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Clinical Therapeutics: Rheumatoid Arthritis; Metabolic Bone Disease ((Current Opinion in Rheumatology Ser.)) by Dwight R. Robinson (1994); ISBN: 1859226442; http://www.amazon.com/exec/obidos/ASIN/1859226442/icongroupinterna
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Connective tissue changes in rheumatoid arthritis and the use of penicillamine : proceedings of a review symposium held in Rotterdam, 9-10 March 1979, under the
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auspices of the "Gerrit Jan Mulder Foundation"; ISBN: 3764311274; http://www.amazon.com/exec/obidos/ASIN/3764311274/icongroupinterna •
Connective Tissue Diseases: Lupus, Scleroderma and Rheumatoid Arthritis by Susan Brown (Editor), Robert P. Sundel (Editor) (1994); ISBN: 187977206X; http://www.amazon.com/exec/obidos/ASIN/187977206X/icongroupinterna
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Conquering Rheumatoid Arthritis (French by William Bensen, Wynn Bensen (1997); ISBN: 0969778198; http://www.amazon.com/exec/obidos/ASIN/0969778198/icongroupinterna
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Conquering Rheumatoid Arthritis: An Illustrated Guide to Understanding the Treatment and Control of Rheumatoid Arthritis by William Md Bensen, et al (1997); ISBN: 096977818X; http://www.amazon.com/exec/obidos/ASIN/096977818X/icongroupinterna
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Conquering Rheumatoid Arthritis: The Latest Breakthroughs and Treatments by Thomas F. Lee (2001); ISBN: 1573928860; http://www.amazon.com/exec/obidos/ASIN/1573928860/icongroupinterna
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Coping With Rheumatoid Arthritis by Robert H. Phillips (1988); ISBN: 0895293714; http://www.amazon.com/exec/obidos/ASIN/0895293714/icongroupinterna
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Diagnosis and Management of Rheumatoid Arthritis by Andrei Calin; ISBN: 0201108100; http://www.amazon.com/exec/obidos/ASIN/0201108100/icongroupinterna
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Differential Diagnosis of Rheumatoid Arthritis by Allan Binder; ISBN: 1858730201; http://www.amazon.com/exec/obidos/ASIN/1858730201/icongroupinterna
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Differential Diagnosis of Rheumatoid Arthritis: Slide Atlas by Allan Binder (Editor); ISBN: 185873021X; http://www.amazon.com/exec/obidos/ASIN/185873021X/icongroupinterna
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Early Rheumatoid Arthritis (Bailliere's Clinical Rheumatology) by A.D. Woolf, P.L.C.M. van Riel; ISBN: 0702022659; http://www.amazon.com/exec/obidos/ASIN/0702022659/icongroupinterna
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Emergencies in Rheumatoid Arthritis by Sheldon P. Blau (Editor) (1986); ISBN: 0879932635; http://www.amazon.com/exec/obidos/ASIN/0879932635/icongroupinterna
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Finding Ways: Recovering from Rheumatoid Arthritis Through Alternative Medicine by Barbara Jay Nies (1997); ISBN: 0965364860; http://www.amazon.com/exec/obidos/ASIN/0965364860/icongroupinterna
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Foot and Ankle in Rheumatoid Arthritis by M. Bouysset (2003); ISBN: 2287597573; http://www.amazon.com/exec/obidos/ASIN/2287597573/icongroupinterna
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Genetic Analysis of Autoimmune Diseases Using Animal Models: Mapping Susceptibility Genes for Multiple Sclerosis and Rheumatoid Arthritis (Comprehensive Summaries of Uppsala Dissertations, 927) by Hai-Tao Yang (2001); ISBN: 9155447171; http://www.amazon.com/exec/obidos/ASIN/9155447171/icongroupinterna
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Genetic Studies of Rheumatoid Arthritis Using Animal Models (Comprehensive Summaries of Uppsala Dissertations from the Faculty of mediciNe, 1074) by Niklas Nordquist (2001); ISBN: 9155451179; http://www.amazon.com/exec/obidos/ASIN/9155451179/icongroupinterna
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Getting Up is Hard to Do : Life with Rheumatoid Arthritis by Wanda James; ISBN: 0968703607; http://www.amazon.com/exec/obidos/ASIN/0968703607/icongroupinterna
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Health Journeys for People With Abridged Rheumatoid Arthritis or Lupus by Belleruth Naparstek (Author) (1994); ISBN: 1570420114; http://www.amazon.com/exec/obidos/ASIN/1570420114/icongroupinterna
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Health Journeys: A Guided Meditation To Help You With Rheumatoid Arthritis Or Lupus by Belleruth Naparstek, Steven M. Kohn; ISBN: 1881405257; http://www.amazon.com/exec/obidos/ASIN/1881405257/icongroupinterna
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Il-1Ra in the Treatment of Rheumatoid Arthritis by Barry Bresnihan, Jean-Michel Dayer (2002); ISBN: 1841841420; http://www.amazon.com/exec/obidos/ASIN/1841841420/icongroupinterna
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Immunological Aspects of Rheumatoid Arthritis: Proceedings of the International Symposium, Montpellier, March, 1974 by J. Clot (Editor) (1975); ISBN: 3805521162; http://www.amazon.com/exec/obidos/ASIN/3805521162/icongroupinterna
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Intraneural Injections for Rheumatoid Arthritis & Osteoarthritis & the Control of Pain in Arthritis by Paul Notrik (1984); ISBN: 0931150140; http://www.amazon.com/exec/obidos/ASIN/0931150140/icongroupinterna
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Joints of Pain : Living my Life with Rheumatoid Arthritis by Laura Pietro; ISBN: 0970418604; http://www.amazon.com/exec/obidos/ASIN/0970418604/icongroupinterna
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Juvenile Rheumatoid Arthritis by Earl Brewer; ISBN: 072161986X; http://www.amazon.com/exec/obidos/ASIN/072161986X/icongroupinterna
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Juvenile rheumatoid arthritis; ISBN: 0884161897; http://www.amazon.com/exec/obidos/ASIN/0884161897/icongroupinterna
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Keeping A Secret: A Story About Juvenile Rheumatoid Arthritis by Elizabeth Murphy Melas, et al; ISBN: 0929173341; http://www.amazon.com/exec/obidos/ASIN/0929173341/icongroupinterna
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Key Advances in Effective Management of Rheumatoid Arthritis by I. Haslock (Editor), et al; ISBN: 1853154938; http://www.amazon.com/exec/obidos/ASIN/1853154938/icongroupinterna
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Living With Juvenile Rheumatoid Arthritis (Living Well Chronic Conditions) by Serge Bloch, Susan Heinrichs Gray; ISBN: 1567661041; http://www.amazon.com/exec/obidos/ASIN/1567661041/icongroupinterna
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Living with Rheumatoid Arthritis by Tammi L. Shlotzhauer, et al; ISBN: 0801871476; http://www.amazon.com/exec/obidos/ASIN/0801871476/icongroupinterna
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Management of Juvenile Rheumatoid Arthritis: A Handbook for Occupational and Physical Therapists by Helen, M.D. Emery, Judy, Otrl. Kucinski; ISBN: 9991189599; http://www.amazon.com/exec/obidos/ASIN/9991189599/icongroupinterna
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Management of rheumatoid arthritis and its complications by James William Hollingsworth; ISBN: 0815146329; http://www.amazon.com/exec/obidos/ASIN/0815146329/icongroupinterna
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Measuring Outcomes of Rheumatoid Arthritis by Andrew F. Long; ISBN: 1860160328; http://www.amazon.com/exec/obidos/ASIN/1860160328/icongroupinterna
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Mechanisms and Models in Rheumatoid Arthritis by J.C.W. Edwards, et al (1995); ISBN: 0123404401; http://www.amazon.com/exec/obidos/ASIN/0123404401/icongroupinterna
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Mechanisms of tissue injury with reference to rheumatoid arthritis; ISBN: 089072010X; http://www.amazon.com/exec/obidos/ASIN/089072010X/icongroupinterna
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New Horizons in Rheumatoid Arthritis: Proceedings of the International Congress on Rheumatoid Arthritis, Hakone, 24-26 August, 1980 by International Congress on Rheumatoid Arthritis; ISBN: 044490185X; http://www.amazon.com/exec/obidos/ASIN/044490185X/icongroupinterna
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Nicole's Story: A Book About a Girl With Juvenile Rheumatoid Arthritis by Virginia Tortorica Aldape, et al (1996); ISBN: 082252578X; http://www.amazon.com/exec/obidos/ASIN/082252578X/icongroupinterna
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Organic manifestations and complications in rheumatoid arthritis : symposium Hernstein November 2nd-5th, 1975; ISBN: 3794505212; http://www.amazon.com/exec/obidos/ASIN/3794505212/icongroupinterna
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Pipeline Insight: Rheumatoid Arthritis and Osteoarthritis - Striving for innovation among me-toos [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00009XGBS; http://www.amazon.com/exec/obidos/ASIN/B00009XGBS/icongroupinterna
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Pocket Reference to TNF Antagonism and Rheumatoid Arthritis by Maini, et al (2000); ISBN: 1858733758; http://www.amazon.com/exec/obidos/ASIN/1858733758/icongroupinterna
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Practical Prescribing Guidelines for Rheumatoid Arthritis by Hilary Capell, et al (2003); ISBN: 1841842826; http://www.amazon.com/exec/obidos/ASIN/1841842826/icongroupinterna
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Psychological Aspects of Rheumatoid Arthritis (1989); ISBN: 3540971165; http://www.amazon.com/exec/obidos/ASIN/3540971165/icongroupinterna
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Psychological Aspects of Rheumatoid Arthritis (Recent Research in Psychology) by Mary L. Pritchard (1989); ISBN: 0387971165; http://www.amazon.com/exec/obidos/ASIN/0387971165/icongroupinterna
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Rehabilitation of Early Rheumatoid Arthritis by Matthew H. Liang, Martha K. Logigian; ISBN: 0316530875; http://www.amazon.com/exec/obidos/ASIN/0316530875/icongroupinterna
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Rehabilitation of Persons with Rheumatoid Arthritis by Rowland W. Chang (Editor), et al; ISBN: 083420679X; http://www.amazon.com/exec/obidos/ASIN/083420679X/icongroupinterna
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Rehabilitation Through Learning: Energy Conservation and Joint Protection Workbook for Persons With Rheumatoid Arthritis With Instructions Guide; ISBN: 0318199203; http://www.amazon.com/exec/obidos/ASIN/0318199203/icongroupinterna
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Revisional Surgery in Rheumatoid Arthritis (Rheumatology: The Interdisciplinary Concept, Vol 13) by M. Hamalainen, et al (1990); ISBN: 380554930X; http://www.amazon.com/exec/obidos/ASIN/380554930X/icongroupinterna
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Rheumatoid Arthritis by Edward D., Jr. Harris, Richard Zorab (Editor); ISBN: 0721652492; http://www.amazon.com/exec/obidos/ASIN/0721652492/icongroupinterna
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Rheumatoid Arthritis by Barton F., Md. Haynes (Editor), et al (2004); ISBN: 0781741491; http://www.amazon.com/exec/obidos/ASIN/0781741491/icongroupinterna
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Rheumatoid Arthritis by Larry W. Moreland, John D. Isaacs (2002); ISBN: 1903734169; http://www.amazon.com/exec/obidos/ASIN/1903734169/icongroupinterna
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Rheumatoid Arthritis by Josef S. Smolen (1992); ISBN: 354053315X; http://www.amazon.com/exec/obidos/ASIN/354053315X/icongroupinterna
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Rheumatoid Arthritis & Related Diseases by Robert P. Sundel; ISBN: 1879772108; http://www.amazon.com/exec/obidos/ASIN/1879772108/icongroupinterna
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Rheumatoid Arthritis (Clinical Symposia, Vol 51, Pt 1) by Allan Jacobs; ISBN: 9999981895; http://www.amazon.com/exec/obidos/ASIN/9999981895/icongroupinterna
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Rheumatoid Arthritis (Contemporary Management in Internal Medicine Ser Vol, 1 No. 6) by Michael Fischbach (Editor); ISBN: 0443088276; http://www.amazon.com/exec/obidos/ASIN/0443088276/icongroupinterna
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Rheumatoid Arthritis (Contemporary Patient Management Series) by Duncan A. Gordon; ISBN: 0874883806; http://www.amazon.com/exec/obidos/ASIN/0874883806/icongroupinterna
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Rheumatoid Arthritis (Current Directions in Autoimmunity, Vol. 3) by J. J. Goronzy (Editor), C. M. Weyand (Editor) (2001); ISBN: 3805571208; http://www.amazon.com/exec/obidos/ASIN/3805571208/icongroupinterna
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Rheumatoid Arthritis (Gurne & Stratton Manuals of Clinical Medicie) by Norman O. Rothermich, Ronald L Whisler; ISBN: 0808917161; http://www.amazon.com/exec/obidos/ASIN/0808917161/icongroupinterna
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Rheumatoid arthritis : cellular pathology and pharmacology : proceedings of the Cambridge Rheumatism Research Group Symposium on Rheumatoid ArthritisCellular Pathology and Pharmacology, held in Cambridge, United Kingdom, 21-23 September 1976; ISBN: 0720406218; http://www.amazon.com/exec/obidos/ASIN/0720406218/icongroupinterna
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Rheumatoid Arthritis and Related Conditions (ARR) by G S Panayi; ISBN: 0443017158; http://www.amazon.com/exec/obidos/ASIN/0443017158/icongroupinterna
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Rheumatoid Arthritis As a Systemic Disease by Ralph C. Williams; ISBN: 0721694179; http://www.amazon.com/exec/obidos/ASIN/0721694179/icongroupinterna
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Rheumatoid Arthritis of the Hand and Elbow by Donald C. Ferlic (1991); ISBN: 0801642825; http://www.amazon.com/exec/obidos/ASIN/0801642825/icongroupinterna
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Rheumatoid Arthritis Surgery of the Complex Hand and Foot (Rheumatology, Vol 11) by F.-W. Hagena (Editor) (1987); ISBN: 3805544081; http://www.amazon.com/exec/obidos/ASIN/3805544081/icongroupinterna
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Rheumatoid Arthritis Surgery of the Elbow (Rheumatology. the Interdisciplinary Concept, Vol 15) by M. J. Hamalainen (Editor), F. W. Hagena (Editor) (1991); ISBN: 3805553277; http://www.amazon.com/exec/obidos/ASIN/3805553277/icongroupinterna
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Rheumatoid Arthritis Surgery of the Shoulder (Rheumatology, Vol 12) by A.W.F. Lettin, et al (1989); ISBN: 3805548044; http://www.amazon.com/exec/obidos/ASIN/3805548044/icongroupinterna
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Rheumatoid Arthritis: A Patient's Guide (Patient Guides) by Ali S.M. Jawad MBChB MRCP DCH DMedRehab; ISBN: 1853173320; http://www.amazon.com/exec/obidos/ASIN/1853173320/icongroupinterna
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Rheumatoid Arthritis: A Separate World, Personal Account of Living With Rheumatoid Arthritis by Eileen Courtenay, Eileen Courtnay (2000); ISBN: 0828320586; http://www.amazon.com/exec/obidos/ASIN/0828320586/icongroupinterna
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Rheumatoid Arthritis: Advances in Inflammation Research by Gerald Weissmann (1982); ISBN: 0890046573; http://www.amazon.com/exec/obidos/ASIN/0890046573/icongroupinterna
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Rheumatoid Arthritis: An Illustrated Guide to Pathology, Diagnosis, and Management by H. Ralph Schumacher, et al; ISBN: 0397446535; http://www.amazon.com/exec/obidos/ASIN/0397446535/icongroupinterna
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Rheumatoid Arthritis: Current Trends in Diagnostic, Conservative Treatment, and Surgical Reconstruction by H. Baumgartner (1995); ISBN: 0865776024; http://www.amazon.com/exec/obidos/ASIN/0865776024/icongroupinterna
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Rheumatoid Arthritis: Current Trends in Diagnostics, Convervative Treatment and Surgical Reconstruction by Hubert Baumgartner (Editor), et al; ISBN: 3131024410; http://www.amazon.com/exec/obidos/ASIN/3131024410/icongroupinterna
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Rheumatoid Arthritis: Epidemiology, Pathogenesis and Treatment by Sherine Gabriel, Larry Moreland (2001); ISBN: 1901346161; http://www.amazon.com/exec/obidos/ASIN/1901346161/icongroupinterna
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Rheumatoid Arthritis: Etiology, Diagnosis, Management by Peter D. Utsinger, et al; ISBN: 0397505884; http://www.amazon.com/exec/obidos/ASIN/0397505884/icongroupinterna
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Rheumatoid Arthritis: Everything You Need to Know by Robert G. Lahita (2001); ISBN: 1583331018; http://www.amazon.com/exec/obidos/ASIN/1583331018/icongroupinterna
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Rheumatoid Arthritis: Frontiers in Pathogenesis and Treatment by Gary S. Firestein (Editor), et al; ISBN: 0192629727; http://www.amazon.com/exec/obidos/ASIN/0192629727/icongroupinterna
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Rheumatoid Arthritis: Pathogenesis, Assessment, Outcome, and Treatment by Frederick Wolfe (Editor), Theodore Pincus (Editor); ISBN: 0824788788; http://www.amazon.com/exec/obidos/ASIN/0824788788/icongroupinterna
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Rheumatoid arthritis: pathogenetic mechanisms and consequences in therapeutics; ISBN: 0125100507; http://www.amazon.com/exec/obidos/ASIN/0125100507/icongroupinterna
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Rheumatoid Arthritis: Plan to Win by Cheryl Koehn, et al (2002); ISBN: 0195130561; http://www.amazon.com/exec/obidos/ASIN/0195130561/icongroupinterna
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Rheumatoid Arthritis: Recent Research Advances by J.R. Kalden, et al (1992); ISBN: 038753315X; http://www.amazon.com/exec/obidos/ASIN/038753315X/icongroupinterna
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Rheumatoid Arthritis: The Infection Connection {Targeting and Treating the Cause of Chronic Illness} by Katherine M. Poehlmann; ISBN: 0961726865; http://www.amazon.com/exec/obidos/ASIN/0961726865/icongroupinterna
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Rheumatoid Arthritis: The Treatment Controversy by David Goddard, Robin Butler (Editor); ISBN: 0333419200; http://www.amazon.com/exec/obidos/ASIN/0333419200/icongroupinterna
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Rheumatoid arthritis: theoretical and clinical aspects; ISBN: 0842271082; http://www.amazon.com/exec/obidos/ASIN/0842271082/icongroupinterna
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Rheumatoid Arthritis: Your Medication Explained (Overcoming Common Problems Series.) by Mary-Claire Mason, Elaine, Dr. Smith; ISBN: 085969836X; http://www.amazon.com/exec/obidos/ASIN/085969836X/icongroupinterna
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Rheumatoid Arthritis: Your Questions Answered by Robert J. Moots, Nigel Jones (2004); ISBN: 0443074429; http://www.amazon.com/exec/obidos/ASIN/0443074429/icongroupinterna
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Selected therapeutic problems in rheumatoid arthritis : international symposium, Geneva 29. 11 - 2. 12. 1973; ISBN: 3541064811; http://www.amazon.com/exec/obidos/ASIN/3541064811/icongroupinterna
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Slide Atlas of Rheumatology: Rheumatoid Arthritis & Spondyloarthropathy by J.H. Klippel, P.A. Dieppe ARC; ISBN: 0723420629; http://www.amazon.com/exec/obidos/ASIN/0723420629/icongroupinterna
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Staff manual for teaching patients about rheumatoid arthritis by Roberta Wallace; ISBN: 0872582523; http://www.amazon.com/exec/obidos/ASIN/0872582523/icongroupinterna
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Staff Manual for Teaching Patients About Rheumatoid Arthritis 1982 Edition by Roberta Wallace; ISBN: 0872583740; http://www.amazon.com/exec/obidos/ASIN/0872583740/icongroupinterna
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Surgery for Rheumatoid Arthritis: A Comprehensive Team Approach by MacK L., M.D. Clayton, Charley J., M.D. Smyth (Editor) (1992); ISBN: 0443082170; http://www.amazon.com/exec/obidos/ASIN/0443082170/icongroupinterna
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Surgery in Rheumatoid Arthritis by Ian F. Goldie (Editor) (1981); ISBN: 380551445X; http://www.amazon.com/exec/obidos/ASIN/380551445X/icongroupinterna
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Surgery of rheumatoid arthritis; ISBN: 0397502834; http://www.amazon.com/exec/obidos/ASIN/0397502834/icongroupinterna
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Surgical Treatment of Rheumatoid Arthritis by Thomas P. Sculco (Editor), et al (1992); ISBN: 0801662796; http://www.amazon.com/exec/obidos/ASIN/0801662796/icongroupinterna
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Surgical Treatment of Rheumatoid Arthritis by N. Gschwend, G. Stiasny (Translator); ISBN: 3135847012; http://www.amazon.com/exec/obidos/ASIN/3135847012/icongroupinterna
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T cells in the inflamed joints of patients with rheumatoid arthritis by Radboud J. E. M. Dolhain; ISBN: 9090115226; http://www.amazon.com/exec/obidos/ASIN/9090115226/icongroupinterna
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The 2002 Official Patient's Sourcebook on Rheumatoid Arthritis by James N. Parker, Icon Health Publications; ISBN: 0597829861; http://www.amazon.com/exec/obidos/ASIN/0597829861/icongroupinterna
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The Arthritis Foundation's Guide to Good Living with Rheumatoid Arthritis by Gretchen Henkel, et al; ISBN: 0912423218; http://www.amazon.com/exec/obidos/ASIN/0912423218/icongroupinterna
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The Course and Outcome of Rheumatoid Arthritis by D. Scott; ISBN: 0702016357; http://www.amazon.com/exec/obidos/ASIN/0702016357/icongroupinterna
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The Hospital for Special Surgery Rheumatoid Arthritis Handbook by Stephen A. Paget (Author), et al; ISBN: 0471410454; http://www.amazon.com/exec/obidos/ASIN/0471410454/icongroupinterna
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The Official Patient's Sourcebook on Juvenile Rheumatoid Arthritis: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 059783377X; http://www.amazon.com/exec/obidos/ASIN/059783377X/icongroupinterna
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The pathology of rheumatoid arthritis by Dugald L. Gardner; ISBN: 0713141948; http://www.amazon.com/exec/obidos/ASIN/0713141948/icongroupinterna
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The Road Back: Rheumatoid Arthritis, Its Cause and Its Treatment by Thomas Mc Pherson Brown, et al (1988); ISBN: 0871315432; http://www.amazon.com/exec/obidos/ASIN/0871315432/icongroupinterna
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The Road Back: Rheumatoid Arthritis: Its Cause & Its Treatment by Thomas M. Brown; ISBN: 0788159100; http://www.amazon.com/exec/obidos/ASIN/0788159100/icongroupinterna
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The Surgical Management of Rheumatoid Arthritis by F. Howard Beddow (1989); ISBN: 072361007X; http://www.amazon.com/exec/obidos/ASIN/072361007X/icongroupinterna
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The Wrist in Rheumatoid Arthritis (Rheumatology: The Interdisciplinary Concept, Vol 17) by B.R. Simmen, F.W. Hagena (Editor) (1992); ISBN: 3805555148; http://www.amazon.com/exec/obidos/ASIN/3805555148/icongroupinterna
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The Year in Rheumatic Disorders 2002: Special Issue: Rheumatoid Arthritis by D. Scott (Editor), et al (2002); ISBN: 0953733998; http://www.amazon.com/exec/obidos/ASIN/0953733998/icongroupinterna
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TNF-Inhibition in the Treatment of Rheumatoid Arthritis by Larry W. Moreland, et al; ISBN: 1841841560; http://www.amazon.com/exec/obidos/ASIN/1841841560/icongroupinterna
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Understanding Osteoarthritis/Rheumatoid Arthritis (Humanatomy, 18) by Tim Peters (1996); ISBN: 1879874717; http://www.amazon.com/exec/obidos/ASIN/1879874717/icongroupinterna
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Understanding Rheumatoid Arthritis by S. P. Newman (Editor) (1996); ISBN: 0415105412; http://www.amazon.com/exec/obidos/ASIN/0415105412/icongroupinterna
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What Your Doctor May Not Tell You About Autoimmune Disorders: The Revolutionary, Drug-Free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic Fatigue; Rheumatoid Arthritis, and Other Diseases by Stephen B./Mitchell Edelson (Author), et al (2003); ISBN: 0446679240; http://www.amazon.com/exec/obidos/ASIN/0446679240/icongroupinterna
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You Asked About Rheumatoid Arthritis by Harold Speers Robinson; ISBN: 0825300886; http://www.amazon.com/exec/obidos/ASIN/0825300886/icongroupinterna
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You asked about rheumatoid arthritis; ISBN: 0888941773; http://www.amazon.com/exec/obidos/ASIN/0888941773/icongroupinterna
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The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “rheumatoid arthritis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
[Beta] 1C-globulin and trypsin inhibitors in systemic lupus erythematosus and rheumatoid arthritis. Author: Lundh, Bengt.; Year: 2003; Lund, Gleerup, 1965
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A prognostic study of juvenile rheumatoid arthritis: analysis of 544 cases. Author: Laaksonen, Anna-Liisa.; Year: 2001; Turku, Jaakkoo-Taara, 1966
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A study on a substance eluted from erythrocytes of patients with rheumatoid arthritis and patients with hemolytic anemia. Author: Blodgett, Randolph C.,; Year: 1948; [Minneapolis] 1963
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Anemia problems in rheumatoid arthritis. Author: Nilsson, Fried Alvar,; Year: 1963; Uppsala, Appelbergs boktryckeriaktiebolag, 1948
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Cellular concepts in rheumatoid arthritis. Comp. and ed. by C. A. L. Stephens, Jr. and A. B. Stanfield with the assistance of Margaret L. Doorly. Author: Stephens, C. A. L.,; Year: 1967; Springfield, Ill., Thomas [c1966]
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Characterization of dextran eluates from erythrocytes of normal persons and patients with rheumatoid arthritis. Author: Hunder, Gene G.; Year: 1965; [Minneapolis] 1965
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Clinical and radiographic findings of the temporomandibular joint in patients with rheumatoid arthritis. Author: Hatch, Gary S.; Year: 1962; [Minneapolis] 1967
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Conference on criteria for, and evaluation of, orthopedic measures in the management of deformities of rheumatoid arthritis, Barbizon Plaza Hotel, New York, December 8, 1963. [Transactions. Author: American Rheumatism Association.; Year: 1962; New York, Grune; Stratton, 1964]
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Copper, zinc, and iron content of synovial fluid from patients with rheumatoid arthritis. Author: Bonebrake, Robert Alan,; Year: 1966; [Minneapolis] 1967
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Radiological aspects of rheumatoid arthritis; proceedings of an international symposium. Editor and translator: Mary E. Carter. Author: Carter, Mary E.; Year: 1965; Amsterdam, New York, Excerpta Medica Foundation [c1964]
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Surgery of rheumatoid arthritis. Author: Marmor, Leonard,; Year: 1965; Philadelphia, Lea; Febiger, 1967
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Synovectomy and arthroplasty in rheumatoid arthritis; 2nd international symposium January 27th-29th 1967 in Basle, Switzerland. Edited by G. Chapchal. Author: Chapchal, George,; Year: 1966; Stuttgart, Thieme, 1967
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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The psychological aspects of rheumatoid arthritis. Author: Geist, Harold,; Year: 1966; Springfield, Ill. Thomas [c1966]
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The psychosomatic approach to primary chronic rheumatoid arthritis; a comparison between primary chronic rheumatoid arthritis and other psychosomatic diseases (bronchial asthma, peptic ulcer, essential hypertension) in relation to a control group of normals, by J. J. G. Prick and K. J. M. van de Loo. Tr. by T. G. Fahy. Author: Prick, J. J. G. (Joseph Jules Guillaume); Year: 1961; Philadelphia, Davis [c1964]
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The surgical management of rheumatoid arthritis [by] Robert L. Preston, with introductory chapters on the general and nonsurgical aspects of rheumatoid arthritis, by Currier McEwen. Author: Preston, Robert L.,; Year: 1966; Philadelphia, London, Saunders [c1968]
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The temporomandibular joint in adult rheumatoid arthritis; a clinical and roentgenologic study. Author: Uotila, Esko.; Year: 1964; Helsinki, 1964
Chapters on Rheumatoid Arthritis In order to find chapters that specifically relate to rheumatoid arthritis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and rheumatoid arthritis using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on rheumatoid arthritis: •
Lessons from Treatment of Rheumatoid Arthritis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 283-288. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email: [email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Rheumatoid arthritis (RA) is a disease of very complex pathophysiology, combining genetic factors, alterations of cellular and humoral immune responses, potential involvement of infectious agents, and various mechanisms of tissue destruction. When compared to inflammatory bowel diseases (IBDs), remarkable similarities both in pathophysiological mechanisms and in management of therapy exist, which may allow one to develop novel strategies for each of these disease entities derived from knowledge of the counterpart. This chapter on lessons from the treatment of RA is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known IBD. In this chapter, the authors offer a chart comparing the similarities of pathophysiologic features of RA and IBD covering genetic factors, involvement of microorganisms, cellular infiltrates, inflammatory mediators, cytokines, immune phenomena, tissue destruction by disease components, tissue destruction by vasculitis or fibrosis (scarring), and extrafocal manifestations. The authors then outline early and long term disease modifying drug treatments and their complications, concluding with a discussion of biologics (monoclonal antibodies and soluble cytokine
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receptors that can inhibit the effects of proinflammatory cytokines). 5 tables. 12 references. •
Immunopathogenesis of Rheumatoid Arthritis Source: in Maddison, P.J. et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 621-638. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals focuses on the immunopathogenesis of rheumatoid arthritis. A historical review of rheumatoid arthritis is presented. Factors involved in the etiology of rheumatoid arthritis are examined, including genetic factors, infectious agents, and sex hormones. Antibodies that show diagnostic specificity for rheumatoid arthritis are identified. The pathology of rheumatoid arthritis is discussed, focusing on involvement of the synovial joints, the development of pannus, and extraarticular manifestations. The pathogenesis of rheumatoid arthritis is described, focusing on cell recruitment, T-cell activation, B-cell lineage, cell interaction, cytokine expression and regulation, and immune suppression. Examples of existing and new models of rheumatoid arthritis are presented. These models include collagen-induced arthritis, adjuvant arthritis, and streptococcal cell-wall arthritis. 151 references, 9 figures, and 2 tables.
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Anti-Cytokine Therapy for Rheumatoid Arthritis Source: in Coggins, C.H. Hancock, E.W. Levitt, L.J., eds. Annual Review of Medicine, Volume 51, 2000. Palo Alto, CA: Annual Reviews, Inc. 2000. p. 207-229. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org. Summary: This chapter provides health professionals with information on anticytokine therapy for rheumatoid arthritis (RA). Although the chapter focuses on studies designed to inhibit the activity of tumor necrosis factor (TNF) alpha and interleukin (IL) 1 in RA, it also considers the preliminary clinical data concerning blockade of IL-6 and strategies to augment the activity of the antiinflammatory cytokines IL-4, IL-10, and IL-11 in this disease. TNF alpha and IL-1 are important in mediating inflammation in RA. The possibility that IL-1 and TNF alpha might be implicated in the pathogenesis of inflammation and joint damage in RA arose from in vitro observations that demonstrated the proinflammatory properties of these cytokines. Both were shown to stimulate production of prostaglandin E and collagenase, and they were implicated in stimulating resorption of cartilage and inhibiting synthesis of proteoglycan. Despite evidence from in vitro experiments, there was considerable skepticism that anti-TNF agents would have significant therapeutic activity in a disease that seems to involve multiple inflammatory pathways with overlapping functions. However, two approaches in preclinical in vivo studies produced convincing data that TNF alpha was a valid therapeutic target. Randomized phase II and III clinical trials of the anti-TNF reagents infliximab and etanercept have demonstrated an acceptable safety profile and marked clinical efficacy in cases of RA that have not responded adequately to conventional therapy. Combination therapy with methotrexate (MTX) appears to be particularly effective in patients whose disease activity persists despite prior disease modifying antirheumatic drugs (DMARDs) and ongoing MTX monotherapy. DMARD recalcitrant disease may become the main indication for the use of anti-TNF drugs in patients with RA. Trials of IL-1 receptor antagonist show a relatively modest antiinflammatory effect
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and a possible retardation of joint damage. Whether anti-TNF therapy protects joints from structural damage is under investigation. One anti-TNF reagent has already been approved in the United States for the treatment of RA, and other cytokine antagonists or agonists are under development. 4 figures, 2 tables, and 78 references. (AA-M). •
Chapter 39-B: Pediatric Rheumatic Diseases: Juvenile Rheumatoid Arthritis and Juvenile Spondyloarthropathies Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 534-542. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This section of a chapter on pediatric rheumatic diseases provides health professionals with information on the epidemiology, clinical features, and treatment of juvenile rheumatoid arthritis (JRA) and juvenile spondyloarthropathies. JRA, a disease with an unknown cause, is the most common form of childhood arthritis. JRA is categorized as systemic, polyarticular, and pauciarticular. These subtypes have different clinical presentations, immunogenetic associations, and clinical courses. Diagnosis is based on data from the medical history, physical examination, and laboratory testing. Diagnostic criteria for JRA are disease onset at less than 16 years of age, persistent arthritis in one or more joints for at least 6 weeks, and exclusion of other types of childhood arthritis. JRA treatment begins during the diagnostic phase and consists of physical, social, and pharmacologic components. The physical component consists of performing range of motion exercises, wearing splints, and teaching joint protection techniques. The social program relates to psychosocial adjustments, school adaptations, and vocational issues. The pharmacologic component focuses on treatment of articular, ocular, and other manifestations of JRA with nonsteroidal antiinflammatory drugs (NSAIDs), methotrexate, etanercept, sulfasalazine, and systemic and intraarticular corticosteroids. The juvenile spondyloarthropathies encompass the discrete clinical entities of juvenile ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthropathies associated with inflammatory bowel disease. Most of the juvenile spondyloarthropathies respond to treatment with NSAIDs. 3 tables and 27 references.
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CHAPTER 8. MULTIMEDIA ON RHEUMATOID ARTHRITIS Overview In this chapter, we show you how to keep current on multimedia sources of information on rheumatoid arthritis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on rheumatoid arthritis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “rheumatoid arthritis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on rheumatoid arthritis: •
What You Should Know About Xerostomia (Dry Mouth) Source: Fairburn, GA: National Oral Cancer Awareness (NOCAP). 199x. (videocassette). Contact: Available from American Dental Hygienists' Association (ADHA). 444 North Michigan Avenue, Suite 3400, Chicago, IL 60611. (800) 243-2342 (press 2) or (312) 4408900. Fax (312) 467-1806. Website: www.adha.org. PRICE: $18.00. Item Number 3917 COM. Summary: This videocassette program describes the problem of xerostomia (dry mouth). The introduction stresses that the health impact of saliva goes far beyond the mouth and includes eating, talking, tooth maintenance, and tasting. The program then features a person with xerostomia describing how it feels to have problems with dry mouth. A brief description of the chemical makeup of salivary and the anatomy of the salivary glands follow. The next section discusses the potential causes of xerostomia, including radiation therapy, especially for cancer of the head and neck; drug effects,
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particularly from antihistamines, tranquilizers, and some blood pressure medications; anxiety or depression, even without drug therapy; dehydration; and systemic diseases, including Sjogren's syndrome, lupus, cystic fibrosis, rheumatoid arthritis, and scleroderma. The narrator stresses that aging itself is not necessarily the cause of xerostomia. Complications of xerostomia include dry lips, burning mouth or tongue, constant thirst, difficulty talking or swallowing, impaired taste, dental caries (cavities), candidiasis (a fungal infection), and problems related to dehydration. Viewers are encouraged to work closely with health care providers to obtain an accurate diagnosis and employ strategies to cope with xerostomia. Treatment encompasses three options: eliminating the cause of the xerostomia, if possible; stimulating the salivary glands with sugar-free chewing gum, oral moisturizers, or the prescription drug pilocarpine; and using other measures to get relief, including saliva substitutes, frequent sips of water, room humidifiers (especially during winter), and lip balm. The program concludes with a reminder that xerostomia results in the need for increased attention to dental hygiene, including increased dental visits, limiting sugar intake, the use of fluoride, and the prevention of candidiasis. The program encourages viewers to learn about xerostomia, seek help, and improve the quality of their lives. •
Just one of the kids: A successful school program for a student with JRA Source: [Boston, MA]: Educational Media Center, Tufts-New England Medical Center. 1994. 1 videotape (11:18 minutes, VHS 1/2 inch). Contact: Available from Educational Media Center, Tufts-New England Medical Center, Boston, MA. Telephone: (617) 956-6672 / fax: (617) 350-8312. Summary: This videotape discusses the additional challenges a child with juvenile rheumatoid arthritis faces in school, what juvenile rheumatoid arthritis is, how it affects children, how it is treated, typical modifications needed in the school program, and students' feelings and social needs. It portrays an adolescent with juvenile rheumatoid arthritis discussing her life. [Funded by the Maternal and Child Health Bureau].
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Health Care Professionals' Guide to Xerostomia Source: Bethesda, MD: Sjogren's Syndrome Foundation, Inc. 1997. (videocassette). Contact: Available from Sjogren's Syndrome Foundation, Inc. 8120 Woodmont Avenue, Suite 530, Bethesda MD 20814-1437. (301) 718-0300 or (800) 475-6473. Fax (301) 718-0322. Website: www.sjogrens.org. PRICE: $29.00. Summary: This videotape program reviews xerostomia (dry mouth). The program begins with an overview of the anatomy and physiology of the salivary glands, followed by a discussion of the three functional roles of saliva: digestion (and taste facilitation), lubrication, and protection (including antimicrobial and pH mechanisms). The narrator notes that saliva is also being used more and more as a diagnostic tool to measure systemic health. The program begins with a physician narrating, then includes interviews with two middle age women who have xerostomia; the interviews focus on the impact xerostomia has on quality of life and on the difficulties of obtaining an accurate diagnosis. The program then details the three causes of xerostomia: medical therapies (including drug side effects, radiation therapy, and surgery or trauma of the salivary glands), systemic disorders (including Sjogren's syndrome, HIV, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, graft versus host disease, sarcoidosis, amyloidosis, cystic fibrosis, and neural disease affecting the salivary glands), and dehydration. The program emphasizes that xerostomia is not a natural
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consequence of the aging process. The program then reviews the clinical signs and oral complications of xerostomia; each is illustrated with a color photograph. Other topics include problems associated with xerostomia, the need for a multidisciplinary team approach to patients with salivary gland dysfunction, diagnostic tests used, treatment options (including chewing activity, oral moisturizing agents, and oral pilocarpine hydrochloride), determining residual salivary gland function, and the behavioral and lifestyle changes that can help patients cope with xerostomia.
Bibliography: Multimedia on Rheumatoid Arthritis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in rheumatoid arthritis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on rheumatoid arthritis (for more information, follow the hyperlink indicated): •
A Look at rheumatoid arthritis [videorecording] Source: MCRH; Year: 1982; Format: Videorecording; Grand Forks, ND: MCRH/UND, c1982
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Extra-articular manifestations of rheumatoid arthritis [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1978; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library], 1978
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Juvenile rheumatoid arthritis [slide] Source: Ellen M. Ginzler, Allen D. Meisel; Year: 1981; Format: Slide; [New York]: Medcom, c1981
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Rheumatoid arthritis: a case study [filmstrip] Source: Trainex Corporation; Year: 1975; Format: Filmstrip; Garden Grove, Calif.: Trainex, p1975
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Rheumatoid arthritis [motion picture] Source: Norman P. Schenker; with scientific collaboration of E.G.L. Bywaters. [et al]; Year: 1963; Format: Motion picture; [New York]: Pfizer, [1963?]
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Rheumatoid arthritis [slide] Source: Allen D. Meisel, Ellen M. Ginzler; Year: 1980; Format: Slide; New York: Medcom, c1980
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Rheumatoid arthritis [slide] Source: by Bruce M. Rothschild; Year: 1984; Format: Slide; [Westport, Conn.]: Medical Education Programs, c1984
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Synovectomy of the knee for rheumatoid arthritis [motion picture] Source: [presented by] the United States Army; Year: 1951; Format: Motion picture; United States: War Office, 1951
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Synovectomy of the proximal interphalangeal joint of the finger in rheumatoid arthritis [motion picture] Source: Alan H. Wilde; Year: 1970; Format: Motion picture; Cleveland: Wilde; [Danbury, Conn.: for loan by Davis & Geck, 1970]
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Systemic (extra-articular) manifestations of rheumatoid arthritis [slide] Source: Duncan S. Owen; Year: 1977; Format: Slide; Richmond: Medical College of Virginia: [for sale by its Learning Resource Centers, 1977]
•
The Diagnosis and management of juvenile rheumatoid arthritis [motion picture] Source: presented by McNeil, McNeil Laboratories; produced by Aegis Productions, Inc; Year: 1978; Format: Motion picture; Fort Washington, Penn.: The Laboratories, c1978
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•
The Knee in rheumatoid arthritis [slide] Source: Alan H. Wilde; Year: 1972; Format: Slide; [New York]: Medcom, c1972
•
The Management of rheumatoid arthritis [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1981; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1981
•
The Patient with rheumatoid arthritis [slide] Source: University of Michigan Medical Center Department of Postgraduate Medicine and Health Professions Education Independent Study Unit; Year: 1975; Format: Slide; Ann Arbor: The University: [for loan or sale by its Medical Center Media Library], c1975
•
Treatment of rheumatoid arthritis including joint fluid analysis and injection [slide] Source: Department of Continuing Medical Education School of Medicine State University of New York at Buffalo, in cooperation with Lakes Area Regional Medical Program; Year: 1975; Format: Slide; Buffalo, N. Y.: Communications in Learning, 1975
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CHAPTER 9. PERIODICALS AND NEWS ON RHEUMATOID ARTHRITIS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover rheumatoid arthritis.
News Services and Press Releases One of the simplest ways of tracking press releases on rheumatoid arthritis is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “rheumatoid arthritis” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to rheumatoid arthritis. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “rheumatoid arthritis” (or synonyms). The following was recently listed in this archive for rheumatoid arthritis: •
Tie2 tyrosine kinase regulates angiogenesis in rheumatoid arthritis Source: Reuters Industry Breifing Date: October 13, 2003
•
Intensive exercise improves functional ability of rheumatoid arthritis patients
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Source: Reuters Medical News Date: October 07, 2003 •
Intense exercise good for rheumatoid arthritis Source: Reuters Health eLine Date: October 07, 2003
•
Autoantibodies predate rheumatoid arthritis onset Source: Reuters Medical News Date: October 03, 2003
•
AstraZeneca drops rheumatoid arthritis and COPD compounds Source: Reuters Industry Breifing Date: October 02, 2003
•
Intensive exercise benefits some patients with rheumatoid arthritis Source: Reuters Medical News Date: September 12, 2003
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Activity level predicts physical fitness in juvenile rheumatoid arthritis Source: Reuters Medical News Date: September 03, 2003
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Smokers have an increased risk of RF-positive rheumatoid arthritis Source: Reuters Medical News Date: August 29, 2003
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BPI and HNP are accumulated in inflamed joints of rheumatoid arthritis patients Source: Reuters Medical News Date: August 28, 2003
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Rheumatoid arthritis activity tied to atherogenic lipid profile Source: Reuters Medical News Date: August 26, 2003
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Chemokine blockade may offer treatment of rheumatoid arthritis Source: Reuters Medical News Date: August 05, 2003
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B lymphocytes rise before relapse of rituximab-treated rheumatoid arthritis Source: Reuters Industry Breifing Date: August 01, 2003
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Osteopontin epitope tied to rheumatoid arthritis Source: Reuters Industry Breifing Date: July 21, 2003
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Fourfold increased risk of tuberculosis seen with rheumatoid arthritis Source: Reuters Medical News Date: July 21, 2003
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IL1-beta levels high in synovium of patients with end-stage rheumatoid arthritis Source: Reuters Medical News Date: July 18, 2003
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Women with rheumatoid arthritis have less favorable disease course than men Source: Reuters Medical News Date: July 11, 2003
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Aventis, Vertex start enrollment of rheumatoid arthritis trial of pralnacasan
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Source: Reuters Industry Breifing Date: July 10, 2003 •
Endostatin improves rheumatoid arthritis in mouse model Source: Reuters Industry Breifing Date: July 08, 2003
•
Cortisol clearance normal in women with rheumatoid arthritis Source: Reuters Medical News Date: July 02, 2003
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Beneficial effects of leflunomide for rheumatoid arthritis sustained in long term Source: Reuters Industry Breifing Date: June 27, 2003
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Use of a feedback system may reduce rheumatoid arthritis disease activity Source: Reuters Industry Breifing Date: June 25, 2003
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Rheumatoid arthritis ups overall death risk: study Source: Reuters Health eLine Date: June 24, 2003
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Postmenopausal rheumatoid arthritis strongly linked with osteoporosis Source: Reuters Medical News Date: June 20, 2003
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New IL-6 receptor blocker promising for rheumatoid arthritis Source: Reuters Industry Breifing Date: June 19, 2003
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Infliximab plus methotrexate effective in early rheumatoid arthritis Source: Reuters Medical News Date: June 19, 2003
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DNA chip study reveals gene clues to rheumatoid arthritis Source: Reuters Medical News Date: June 19, 2003
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New study will test Remicade for preventing rheumatoid arthritis Source: Reuters Industry Breifing Date: June 18, 2003
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Leflunomide comparable to sulfasalazine and methotrexate in rheumatoid arthritis Source: Reuters Industry Breifing Date: June 18, 2003
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FDA clears leflunomide for expanded rheumatoid arthritis indication Source: Reuters Medical News Date: June 17, 2003
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Aventis' Arava wins new rheumatoid arthritis indication Source: Reuters Industry Breifing Date: June 17, 2003
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Synovial macrophage elimination could be useful in rheumatoid arthritis Source: Reuters Medical News Date: June 02, 2003
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Dynamic MRI can discriminate active from inactive rheumatoid arthritis
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Source: Reuters Medical News Date: May 29, 2003 •
Smaller babies, smaller rheumatoid arthritis risk Source: Reuters Health eLine Date: May 16, 2003
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Perinatal factors may influence risk of rheumatoid arthritis later in life Source: Reuters Medical News Date: May 15, 2003
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Folate supplement improves response to methotrexate in rheumatoid arthritis Source: Reuters Industry Breifing Date: May 12, 2003
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Autoantibodies are prognostic of erosive disease in early rheumatoid arthritis Source: Reuters Medical News Date: May 08, 2003
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Rheumatoid arthritis associated with arterial stiffness Source: Reuters Medical News Date: May 07, 2003
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Novel cytokine tied to rheumatoid arthritis Source: Reuters Medical News Date: April 29, 2003
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Anakinra seen safe in typical rheumatoid arthritis patients with comorbidities Source: Reuters Industry Breifing Date: April 25, 2003
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Plasma vitamin B6 levels correlate inversely with rheumatoid arthritis severity Source: Reuters Medical News Date: April 23, 2003
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Anti-rheumatoid arthritis drug antibodies compromise medication efficacy Source: Reuters Medical News Date: April 18, 2003
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Etidronate may exert antiinflammatory effect in rheumatoid arthritis Source: Reuters Industry Breifing Date: April 09, 2003
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Smoking linked to increased risk of rheumatoid arthritis in men Source: Reuters Medical News Date: March 31, 2003
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Smoking boosts men's risk of rheumatoid arthritis Source: Reuters Medical News Date: March 27, 2003
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Pleiotrophin upregulated in rheumatoid arthritis synovial membrane Source: Reuters Medical News Date: March 27, 2003
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Smoking boosts men's risk for rheumatoid arthritis Source: Reuters Health eLine Date: March 26, 2003
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No link seen between hepatitis C and rheumatoid arthritis in older adults
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Source: Reuters Medical News Date: March 24, 2003 The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “rheumatoid arthritis” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “rheumatoid arthritis” (or synonyms). If you know the name of a company that is relevant to rheumatoid arthritis, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “rheumatoid arthritis” (or synonyms).
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Newsletters on Rheumatoid Arthritis Find newsletters on rheumatoid arthritis using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “rheumatoid arthritis.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Use of Low-Dose Prednisone in the Management of Rheumatoid Arthritis, The Source: Bulletin on the Rheumatic Diseases. 50(12): 1-4. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on the use of low dose prednisone, a glucocorticoid, in the management of rheumatoid arthritis (RA). RA, a chronic, symmetric polyarthritis that can lead to joint deformity and destruction, is associated with a significant increase in economic loss, morbidity, and mortality. Glucocorticoids have been used in the treatment of RA since 1948. These 21 carbon steroid molecules activate a cytoplasmic glucocorticoid receptor that ultimately results in the prevention of gene expression of various proinflammatory proteins and the inhibition of class I and II major histocompatibility complexes, adhesion molecules, inducible nitric oxide, and cyclooxygenase 2 enzyme. The side effects of glucocorticoids are well known. However, side effects can be minimized by using low doses. Potential side effects of low dose prednisone are osteopenia, bruising, weight gain, and formation of either cataracts or glaucoma. The article reviews evidence demonstrating the effectiveness of low dose corticosteroids in managing RA and suggests appropriate dosing. The article recommends that prednisone, at a dose not to exceed 10 milligrams per day be initiated as early as possible in the treatment of RA, usually with another disease modifying antirheumatic drug. 1 table and 22 references.
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on rheumatoid arthritis: •
Tufts Nutrition Research: From the Lab to Your Plate. Vitamin E for Easing Rheumatoid Arthritis Pain Source: Tufts University Health and Nutrition Letter. 18(12). Special Supplement. February 2001. Contact: 10 High Street, Suite 706, Boston, MA 02110. [email protected] www.healthletter.tufts.edu.
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Summary: This article reviews research suggesting that large doses of vitamin E may help reduce pain and inflammation in people who suffer from rheumatoid arthritis. Two German studies have found that those who take vitamin E daily experience a decrease in morning stiffness, joint tenderness, and joint pain. A Danish study suggests that high enough blood levels of vitamin E may help to prevent rheumatoid arthritis. Danish researchers have found that those who start with low blood levels of vitamin E are eight times more likely than those with higher levels to end up with the disease. This may occur because people with rheumatoid arthritis use up more antioxidants (such as vitamin E) to destroy free radicals (toxic oxygen molecules involved in causing inflammation). Jeffrey Blumberg, head of the Antioxidants Research Laboratory at Tufts University, states that although vitamin E is not the new arthritis treatment, it may be an 'adjunctive treatment.' •
Dangers of Low-dose Corticosteroid Therapy in Rheumatoid Arthritis Source: Bulletin on the Rheumatic Diseases. 46(4):1-4; June 1997. Contact: Arthritis Foundation. 1330 West Peachtree Street; Atlanta, GA 30309. (404) 8727100. Fax (404) 872-9559. Summary: This newsletter article for health professionals considers the adverse effects of oral low-dose corticosteroid therapy in rheumatoid arthritis, focusing on osteoporosis and posterior subcapsular cataracts. Concerns related to corticosteroid use are discussed, including continued use once they are started and use of higher doses to maintain improvements. In addition, indications for low-dose steroid use are identified and recommendations for steroid use are presented, including using prednisone or prednisolone, using one dose per day rather than split doses, and considering risk factors for the development or aggravation of comorbid conditions. 19 references and 1 table.
•
Juvenile Rheumatoid Arthritis: A Medical Perspective Source: Arthritis Frontline. Winter 2001. Page 4. Contact: Available from Arthritis Foundation, Metropolitan Washington Chapter. 4455 Connecticut Avenue, NW, Suite 300, Washington, DC 20008. (202) 537-6800. E-mail: [email protected]. Website: www.arthritis.org. Summary: This newsletter article provides children who have juvenile rheumatoid arthritis (JRA) and their families with information on this inflammatory condition of the joints. JRA begins before the age of 16. It is categorized into pauciarticular, polyarticular, and systemic subgroups. Approximately half of all children with JRA have pauciarticular JRA, a form in which one to four joints are involved. In most children with this form of JRA, the course of arthritis is intermittent and mild. When more than four joints are involved, the joints tend to be symmetrically affected. Approximately 40 percent of all children with JRA have this polyarticular form of the disease. Polyarticular JRA is more likely found in girls, and most have a mild course. The systemic form affects both genders equally and accounts for 10 percent of JRA cases. There is no definitive test for JRA, so diagnosis is by exclusion. Fifty percent of children with JRA continue to have disease activity into adulthood. Treatments that can stop or slow the progression of the disease include nonsteroidal antiinflammatory drugs, disease modifying antirheumatic drugs, and biologic response modifiers. In addition, children who have JRA should exercise, rest, and use splints to keep the joints functional and the muscles strong.
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•
Genetics and Rheumatic Diseases: Rheumatoid Arthritis and Ankylosing Spondylitis Source: Bulletin on the Rheumatic Diseases. 50(2): 1-4. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter article provides health professionals and patients with information on the genetics of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The article explains the approaches that researchers can take to identify the nonHLA (Human Leukocyte Antigens) genes involved in susceptibility to RA, focusing on the genome wide approach. The article also highlights genetic studies of RA and AS. Analysis of data collected by the European Consortium for RA Families suggests links to several genetic regions. Findings of research conducted by the North American Rheumatoid Arthritis Consortium have revealed the presence of at least six different genetic regions outside the major histocompatibility complex with evidence for linkage. Modeling of genetic data obtained from family studies of AS suggests that two to six independent genes, including HLA-B27, interact multiplicatively to determine the risk for AS. The article discusses the relevance of genetic research on RA and AS to clinical practice. 20 references.
•
Tumor Necrosis Factor Inhibitors for Rheumatoid Arthritis Source: Bulletin on the Rheumatic Diseases. 48(3): 1-4. 1999. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides people who have arthritis with information on the efficacy and safety of etanercept and infliximab for treating rheumatoid arthritis (RA). These new agents are tumor necrosis factor (TNF) antagonists that block the actions of TNF, a cytokine that mediates the clinical and pathologic sequelae of RA. The article explains the immunobiology of TNF and discusses its role in RA. The article then highlights studies on etanercept and infliximab. Studies of etanercept have demonstrated its efficacy in arthritis. A study investigating combination therapy with etanercept and methotrexate in people with RA unresponsive to moderate doses of methotrexate also showed promise. In a study evaluating etanercept in children with juvenile RA, children receiving treatment with etanercept had significant clinical improvement as defined by standard arthritis activity criteria of the pediatric population. Both open label and placebo controlled trials have demonstrated the effectiveness of using infliximab to treat RA. Etanercept has been approved by the Food and Drug Administration (FDA) for use in people with moderate to severe RA who fail to respond to treatment with a disease modifying antirheumatic drug. FDA approval for the use of infliximab in RA is pending. Adverse affects of TNF inhibitors include injection site reactions, development of antibodies to the TNF inhibitor, development of antinuclear and anti-DS DNA antibodies, infections, and lymphomas. 1 table and 16 references.
Academic Periodicals covering Rheumatoid Arthritis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to rheumatoid arthritis. In addition to these sources, you can search for articles covering rheumatoid arthritis that have
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been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for rheumatoid arthritis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with rheumatoid arthritis. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).
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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to rheumatoid arthritis: Azathioprine •
Systemic - U.S. Brands: Imuran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202077.html
Capsaicin •
Topical - U.S. Brands: Zostrix; Zostrix-HP http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202626.html
Chloroquine •
Systemic - U.S. Brands: Aralen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202133.html
Cyclophosphamide •
Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html
Cyclosporine •
Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.html
Gold Compounds •
Systemic - U.S. Brands: Myochrysine; Ridaura; Solganal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202264.html
Histamine H 2 -Receptor Antagonists •
Systemic - U.S. Brands: Axid; Axid AR; Mylanta AR Acid Reducer; Pepcid; Pepcid AC Acid Controller; Pepcid I.V. Pepcid RPD; Tagamet; Tagamet HB; Zantac; Zantac EFFERdose Granules; Zantac EFFERdose Tablets http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202283.html
Infliximab •
Systemic - U.S. Brands: Remicade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203667.html
Leflunomide •
Systemic - U.S. Brands: Arava http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203680.html
Methotrexate for Noncancerous Conditions •
Systemic - U.S. Brands: Folex; Rheumatrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202356.html
Penicillamine •
Systemic - U.S. Brands: Cuprimine; Depen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202445.html
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Rofecoxib •
Systemic - U.S. Brands: Vioxx http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203782.html
Sucralfate •
Oral - U.S. Brands: Carafate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202533.html
Sulfasalazine •
Systemic - U.S. Brands: Azulfidine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202537.html
Tetracyclines •
Systemic - U.S. Brands: Achromycin V; Declomycin; Doryx; Dynacin; Minocin; Monodox; Terramycin; Vibramycin; Vibra-Tabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202552.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
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Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to rheumatoid arthritis by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “rheumatoid arthritis” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for rheumatoid arthritis: •
human gammaglobulin http://www.rarediseases.org/nord/search/nodd_full?code=1114
•
Interleukin-1 receptor antagonist, human recombina (trade name: Antril) http://www.rarediseases.org/nord/search/nodd_full?code=124
•
Methotrexate (trade name: Rheumatrex) http://www.rarediseases.org/nord/search/nodd_full?code=114
•
human gammaglobulin (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1166
•
Immune globulin intravenous (human) (trade name: Iveegam, Immuno) http://www.rarediseases.org/nord/search/nodd_full?code=51
•
Purified type II collagen (trade name: Colloral) http://www.rarediseases.org/nord/search/nodd_full?code=448
•
Gammalinolenic acid http://www.rarediseases.org/nord/search/nodd_full?code=716
•
Interferon Beta-1a (trade name: Avonex) http://www.rarediseases.org/nord/search/nodd_full?code=941
•
Recombinant human tumor necrosis factor receptor f (trade name: Enbrel) http://www.rarediseases.org/nord/search/nodd_full?code=945
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If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “rheumatoid arthritis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. The following is a sample result: •
Disability Statistics Report (14): Mobility Device Use in the United States Source: Washington, DC: U.S. Department of Education, National Institute on Disability and Rehabilitation Research. 2000. 60 p. Contact: Available from U.S. Department of Education, OSERS, National Institute on Disability and Rehabilitation Research (NIDRR). Attn: David Keer. Switzer Building, Room 3431, Washington, DC 20202. (202) 205-5633. E-mail: [email protected]. Website: www.ed.gov/offices/OSERS/NIDRR. Summary: This report provides health professionals, community service professionals, and people who have disabilities with information on mobility device use in the United States. The report provides data on the population using mobility devices, focusing on their age, gender, race and ethnicity, educational attainment, employment and labor force participation, family income, and area of residence. This is followed by data on health and disability status, including self reported health status, hospitalization history, perceived disability status, activity limitation, functional limitation, activities of daily living, and instrumental activities of daily living. The report also examines health conditions and impairments associated with mobility device use. The leading conditions associated with mobility device use among persons of all ages include osteoarthritis (OA) and allied disorders, cerebrovascular disease, orthopedic impairment of a lower extremity, orthopedic impairment of the back or neck, intervertebral disc disorders, senility without psychosis, heart disease, rheumatoid arthritis and other inflammatory polyarthropathies, orthopedic impairment of the hip or pelvis, and chronic injuries. OA is the top ranked condition responsible for disability among users of canes, walkers, and crutches. OA, the most prevalent main cause of disability among mobility device users of all ages, is also the primary cause of disability among working age adults and the elderly. The report concludes with data on accessibility features and problems both inside and outside the home and on health insurance coverage. 24 figures, 26 tables, and 5 references.
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Physical Activity and Health. A Report of the Surgeon General Source: Atlanta, GA: Department of Health and Human Services. 1996. 298 p.
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Contact: Superintendent of Documents, P.O. Box 371954, Pittsburgh, PA 15250-7954. Summary: This report provides information about the relationship between physical activity and health. Chapter one offers introductory information and summarizes conclusions. Chapter two examines the historical development of physical activity promotion as a means of improving health. Chapter three explores physiologic responses and long-term adaptations to exercise. Chapter four focuses on the effects of physical activity and cardiorespiratory fitness with regard to various health problems, including osteoarthritis and osteoporosis. Studies on physical activity in persons with arthritis and on the biologic effects of physical activity on the health and function of joints are highlighted. Results indicate that regular moderate exercise programs appear to relieve symptoms and improve function among people with both osteoarthritis (OA) and rheumatoid arthritis. Although no evidence demonstrates that physical activity causes OA, certain sports-related injuries have been shown to increase the risk of developing OA. Studies on physical activity and osteoporosis are identified. Results show that weight-bearing physical activity appears to build greater bone mass in childhood and early adolescence and maintain bone mass in adulthood. Research on physical activity and the prevention of fractures and falls is also highlighted. Findings indicate that physical activity appears to protect against falling, thus reducing the occurrence of fractures. Remaining chapters present data on patterns and trends in physical activity and review efforts to increase physical activity. Numerous references, 11 figures, and 38 tables. •
Special Report: Arthritis Source: Boston, MA: Harvard Medical School. 1999. 46 p. Contact: Available from Harvard Medical School. Health Publications Group, Department SR, P.O. Box 380, Boston, MA 02117-0380. PRICE: $16.00 plus shipping and handling. Summary: This report provides people who have arthritis with information on the features, diagnosis, and treatment of osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). The report begins by explaining the difference between arthritis and rheumatism. This is followed by an overview of the joints and the immune system in rheumatic diseases. Topics include types of joints, joint design, the functioning of the immune system, the occurrence of inflammation in arthritis, and the role of genetics. The report then discusses OA, RA, and AS in terms of their evolution, symptoms, possible causes, diagnosis, and treatment. Other seronegative spondyloarthropathies, including Reiter's syndrome, psoriatic arthritis, and enteropathic arthritis, are described. A section of the report is devoted to the diagnosis of rheumatic diseases, focusing on obtaining a medical history; assessing pain and stiffness; conducting a physical examination by observing how the patient moves, examining the joints for abnormalities, and moving the joints through their range of motion to detect pain, resistance, unusual sounds, and instability; and performing studies such as blood tests, radiography, other imaging techniques, and arthrocentesis. Another section focuses on using physical therapy to treat people who have arthritis. Modalities discussed are heat and cold therapy, exercise, diathermy, and transcutaneous electrical nerve stimulation. In addition, the report provides suggestions on living with arthritis. They focus on diet; rest during periods of acute inflammation; exercise; joint protection; and ways of coping with depression, stress, and sexual needs. The report also includes a glossary and a list of resources. 1 appendix and 8 figures.
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The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “rheumatoid arthritis” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 76016 920 612 69 16 77633
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “rheumatoid arthritis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
21
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on rheumatoid arthritis can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to rheumatoid arthritis. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to rheumatoid arthritis. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “rheumatoid arthritis”:
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Guides on rheumatoid arthritis Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/tutorials/rheumatoidarthritisloader.html
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Other guides Ankylosing Spondylitis http://www.nlm.nih.gov/medlineplus/ankylosingspondylitis.html Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation.html Juvenile Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/juvenilerheumatoidarthritis.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.html Spleen Diseases http://www.nlm.nih.gov/medlineplus/spleendiseases.html Stem Cells/Stem Cell Transplantation http://www.nlm.nih.gov/medlineplus/stemcellsstemcelltransplantation.html
Within the health topic page dedicated to rheumatoid arthritis, the following was listed: •
General/Overviews Juvenile Rheumatoid Arthritis Source: Nemours Foundation http://kidshealth.org/kid/health_problems/bone/juv_rheum_arthritis.html Juvenile Rheumatoid Arthritis (JRA) Source: Arthritis Foundation http://www.arthritis.org/conditions/DiseaseCenter/jra.asp
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Diagnosis/Symptoms Antinuclear Antibody Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/ana/test.html Rheumatoid Factor Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/rheumatoid/test.html
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Treatment 2003 Drug Guide Source: Arthritis Foundation http://www.arthritis.org/conditions/DrugGuide/default.asp
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Arthritis: Timely Treatments for an Ageless Disease Source: Food and Drug Administration http://www.fda.gov/fdac/features/2000/300_arth.html Help Your Arthritis Treatment Work http://www.fda.gov/opacom/lowlit/arthrtis.html Kids Need Medications, Too Source: Arthritis Foundation http://www.arthritis.org/conditions/DrugGuide/kids.asp Methotrexate Source: American Academy of Family Physicians http://familydoctor.org/handouts/628.html •
Nutrition Nutrition & Diet Source: Arthritis Foundation http://www.arthritis.org/communities/juvenile_arthritis/diet.asp
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Coping Coping with Juvenile Rheumatoid Arthritis Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=301&topcategory=Pedia trics&all=all Dealing with Emotional Issues Source: Arthritis Foundation http://www.arthritis.org/communities/juvenile_arthritis/emotions.asp School Success Source: Arthritis Foundation http://www.arthritis.org/resources/school_success.asp
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Specific Conditions/Aspects Dental Care Source: Arthritis Foundation http://www.arthritis.org/conditions/dentalcare.asp Eye Care Source: Arthritis Foundation http://www.arthritis.org/conditions/DiseaseCenter/JRA/treated_eye_dental_diet. asp Financial Assistance Source: Arthritis Foundation http://www.arthritis.org/communities/juvenile_arthritis/financial.asp Juvenile Arthritis - Other Types and Related Conditions Source: Arthritis Foundation http://www.arthritis.org/conditions/DiseaseCenter/ja_other.asp
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Juvenile Enteropathic Arthritis Source: Arthritis Foundation http://www.arthritis.org/conditions/diseasecenter/juvenileenteropathicarthritis.a sp Juvenile Reactive Arthritis Source: Arthritis Foundation http://www.arthritis.org/conditions/diseasecenter/juvenilereactivearthritis.asp Pauciarticular JRA Source: Arthritis Foundation http://www.arthritis.org/conditions/diseasecenter/pauciarticularJRA.asp Polyarticular JRA Source: Arthritis Foundation http://www.arthritis.org/conditions/diseasecenter/polyarticularJRA.asp Resources for Good Living: Product & Services Directory Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/bg04listings/default.asp Systemic Onset JRA Source: Arthritis Foundation http://www.arthritis.org/conditions/diseasecenter/systemiconsetJRA.asp •
Law and Policy Federal Laws That Can Help Source: Arthritis Foundation http://www.arthritis.org/communities/juvenile_arthritis/federallaws.asp
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Organizations American College of Rheumatology http://www.rheumatology.org/ Arthritis Foundation http://www.arthritis.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/
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Research Pain of Juvenile Arthritis May Reduce School and Social Activity Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ne/highlights/spotlight/2003/pain-juvenile.htm Progress and Opportunities in Juvenile Arthritis Source: Arthritis Foundation http://www.arthritis.org/research/research_program/Juvenile_Arthritis/default.a sp
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the
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exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on rheumatoid arthritis. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Handout on Health: Rheumatoid Arthritis Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1998. 36 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail: [email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-13HH (booklet), or AR-13L HH (large print). Summary: This booklet is for people with rheumatoid arthritis (RA), family members, friends, and others and focuses on the features, progression, causes, diagnosis, and treatment of RA. It discusses the prevalence of the disease, the factors that may have a role in its development, how it differs from other kinds of arthritis, and its progression in the cartilage and bone within the joint. The booklet also explains how a doctor makes a diagnosis, the treatment goals and options, the importance of routine medical care, and some alternative therapies that may help patients cope with the stress of living with a chronic illness. The booklet also describes current research on the causes and treatments for RA by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other components of the National Institutes of Health. It then refers the reader to the network of voluntary health organizations for additional information about RA. A large print version of this booklet is also available. 1 figure.
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Rheumatoid Arthritis Source: Atlanta, GA: Arthritis Foundation. 1998. 24 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. http://www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call 800-283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This brochure for people with rheumatoid arthritis (RA) uses a question and answer format to provide an overview of this common form of arthritis. It explains the differences between RA and other forms of arthritis; discusses the role of heredity, infection, and immune system dysfunction; and describes the disease progression, diagnosis, and treatment. Diagnosis is based on the medical history, a physical
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examination, and tests. Treatment includes medications, exercise, physical therapy, surgery, and diet. Medications that may relieve symptoms are nonsteroidal antiinflammatory drugs, such as aspirin, other analgesics, glucocorticoids, and diseasemodifying medications. In addition, the brochure highlights research on RA, offers advice on managing it, and provides information on the Arthritis Foundation. 2 figures. •
Rheumatoid Arthritis of the Foot and Ankle Source: American Academy of Orthopaedic Surgeons. December 2001. 3 p. Contact: Available from American Academy of Orthopaedic Surgeons. Website: www.familydoctor.org. Summary: This fact sheet discusses the symptoms of and treatment for rheumatoid arthritis (RA) of the foot and ankle. The main symptoms of foot or ankle RA are pain, swelling, and stiffness. The appearance of these symptoms may be the first indication that a patient has RA, or they may occur as the disease spreads through the body. The symptoms often start in the toes or forefoot first, and then spread into the back of the foot. Corns, bunions, claw toe, or hammer toe may develop. Medications can be given to control pain, relieve swelling and inflammation, or help slow the spread of the disease. Special shoes with a deep toe box, arch supports, molded ankle-foot orthotics, canes, or crutches may also be needed. Surgery can be used to correct bunions and hammer toes. Foot fusion (arthrodesis) or joint replacement can be performed to help maintain function and eliminate pain.
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Questions and Answers About Juvenile Rheumatoid Arthritis Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2001. 24 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail: [email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-112QA (booklet), or AR-112L QA (large print). Summary: This fact sheet for children with juvenile rheumatoid arthritis (JRA) and their families uses a question and answer format to provide information. JRA is described as an autoimmune disorder, the most common type of arthritis to affect children, and different from adult rheumatoid arthritis in that, unlike adults, many children outgrow the illness. The fact sheet discusses the most common symptoms of JRA, when they occur, and that children with JRA may look different because of growth problems and the effects of medication. Also explained are diagnostic procedures and treatments including medications such as nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, methotrexate, and corticosteroids. Family support is emphasized, as is the importance of exercise to reduce the symptoms of JRA and maintain joint function and range of motion. Current research on the causes and treatments for JRA is also described, including information about a research registry for families in which two or more siblings have JRA. Readers can get additional information about JRA from the voluntary health organizations listed. A large print version of this fact sheet is also available.
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Living With Rheumatoid Arthritis Source: San Bruno, CA: StayWell Company. 1997. 6 p.
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Contact: Available from StayWell Company. 1100 Grundy Lane, San Bruno, CA 940663030. (800) 333-3032. Website: www.staywell.com. PRICE: Call or write for current pricing on single and bulk orders. Summary: This illustrated brochure provides people who have rheumatoid arthritis (RA) with information on controlling joint pain and inflammation. RA affects the lining of the joints and causes pain, swelling, and stiffness. If untreated, RA can damage joints so badly that they no longer function. Although RA can affect most joints, common sites are the fingers, wrists, elbows, knees, and balls of the feet. Diagnosis is based on information obtained through a medical history, a physical examination, and imaging tests. The brochure outlines the symptoms, offers tips to help reduce symptoms, and provides suggestions on exercising. In addition, the brochure identifies special tools and aids, presents tips on taking medications, and briefly discusses surgery. •
New Arthritis Drugs for Rheumatoid Arthritis and Osteoarthritis Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2000. 5 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 toll-free or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail: [email protected]. Website: www.niams.nih.gov. PRICE: Single copy free. Order Number: AR-210. Summary: This information sheet provides people who have arthritis with information on new drugs that are presently available or awaiting approval for the treatment of rheumatoid arthritis (RA) and osteoarthritis (OA). Biological response modifiers for RA include Enbrel (etanercept) and Remicade (infliximab). Disease modifying antirheumatic drugs for RA include Arava (leflunomide). Nonsteroidal antiinflammatory drugs include Celebrex (celecoxib) and Vioxx (rofecoxib). Among other products are hyaluronic acid viscosupplementation products such as Hyalgan (hyaluronan) and Synvisc (hyland G-F20) and the Prosorba Column (apheresis). For each drug or product, the information sheet lists its name, how it is taken, its most common side effects, its approval status, and its manufacturer. The information sheet also lists additional resources. The National Guideline Clearinghouse™
The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “rheumatoid arthritis” (or synonyms). The following was recently posted: •
Clinical practice guideline for the management of rheumatoid arthritis Source: Advanced Research Techniques in the Health Services - Private For Profit Research Organization; 2001; 170 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3683&nbr=2909&a mp;string=rheumatoid+AND+arthritis
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Guidelines for ophthalmologic examinations in children with juvenile rheumatoid arthritis Source: American Academy of Pediatrics - Medical Specialty Society; 1993 August (reaffirmed 1999); 4 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1772&nbr=998&am p;string=rheumatoid+AND+arthritis
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Management of early rheumatoid arthritis. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 December; 44 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2914&nbr=2140&a mp;string=rheumatoid+AND+arthritis
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Pain in osteoarthritis, rheumatoid arthritis, and juvenile chronic arthritis Source: American Pain Society - Professional Association; 2002; 179 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3691&nbr=2917&a mp;string=rheumatoid+AND+arthritis Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Celebrex Summary: Celebrex is used to relieve the signs and symptoms of osteoarthritis and rheumatoid arthritis in adults. Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6975
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Chinese Thunder God Vine Gives Relief from Rheumatoid Arthritis Symptoms Summary: The roots of Thunder God Vine, a plant whose leaves and flowers are highly toxic, have been used medicinally in China for over 400 years. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7458
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•
Handout on Health: Rheumatoid Arthritis Summary: The booklet describes how rheumatoid arthritis develops, how it is diagnosed, how it is treated and what patients can do to help manage the disease. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3779
•
Questions and Answers About Arthritis and Exercise Summary: This fact sheet answers general questions about arthritis and exercise and includes specific information for the patient with Rheumatoid Arthritis. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=1459
•
Questions and Answers about Juvenile Rheumatoid Arthritis Summary: Juvenile rheumatoid arthritis is arthritis that causes joint inflammation and stiffness for more than 6 weeks in a child of 16 years of age or less. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6724 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to rheumatoid arthritis. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
Associations and Rheumatoid Arthritis The following is a list of associations that provide information on and resources relating to rheumatoid arthritis: •
American Autoimmune Related Diseases Association, Inc Telephone: (586) 776-3900 Fax: (586) 776-3903 Email: [email protected] Web Site: http://www.aarda.org/ Background: The American Autoimmune Related Diseases Association, Inc. (AARDA) is a national not-for-profit voluntary health agency dedicated to bringing a national focus to autoimmunity, a major cause of serious chronic diseases. The Association was founded for the purposes of supporting research to find a cure for autoimmune diseases and providing services to affected individuals. In addition, the Association s goals include increasing the public s awareness that autoimmunity is the cause of more than 80 serious chronic diseases; bringing national focus and collaborative effort among state and national voluntary health groups that represent autoimmune diseases; and serving as a national advocate for individuals and families affected by the physical, emotional, and financial effects of autoimmune disease. The American Autoimmune Related Diseases Association produces educational and support materials including fact sheets, brochures, pamphlets, and a newsletter entitled 'In Focus.'.
•
American Juvenile Arthritis Organization Telephone: (404) 872-7100 Toll-free: (800) 283-7800 Fax: (404) 872-9559 Email: [email protected] Web Site: http://www.arthritis.org Background: The American Juvenile Arthritis Organization (AJAO), a not-for-profit organization, is a Council of the Arthritis Foundation devoted to serving the needs of children, teens, and young adults with childhood rheumatic diseases and their families. These diseases include juvenile rheumatoid arthritis, lupus (systemic lupus erythematosis), ankylosing spondylitis and other related conditions. Juvenile arthritis is medically different from the adult form of arthritis and may be far more severe in some cases. The American Juvenile Arthritis Organization was founded in 1981 to help serve the special needs of affected individuals and families, friends, and health care professionals. The Organization enables members to exchange ideas and support and serves as a clearinghouse of information for the public on topics from medications to educational rights to social services. It sponsors an annual conference; monitors and promotes legislation that benefits individuals with Juvenile Arthritis; provides appropriate referrals; and sponsors research concerning potential causes, improved treatments, preventive measures, and possible cures. The American Juvenile Arthritis
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Organization provides a variety of educational materials including a quarterly newsletter and educational brochures. •
Arthritis Foundation of Australia Telephone: 02 221 2456 Fax: 02 232 2538 Web Site: http://www.span.com.au/arthritis/ Background: The Arthritis Foundation of Australia is a not-for-profit organization that is committed to providing care, education, and research for people affected by arthritis and other musculoskeletal disorders. The term arthritis, meaning inflammation of the joints, may encompass several conditions or disease states, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, gout, and others. The Arthritis Foundation of Australia, which was founded in 1949, is dedicated to promoting research into the causes, control, and cure of arthritis; supporting the professional education and training of physicians and allied health professionals; and enhancing community awareness of the needs of those affected by arthritis. The Foundation's additional objectives include representing people with arthritis nationally and internationally, serving as national secretariat of affiliated state and territory foundations, and assisting affiliated foundations in promoting self-management programs for people with arthritis. The Arthritis Foundation of Australia currently consists of eight state and territory affiliates. These affiliated foundations offer a wide range of services to their members and represent their interests to their own state and territory governments. Each affiliated foundation may also provide the addresses of a wide network of branches and self-help groups in each state.
•
Association Paulette Ghiron-Bistagne Contre L'Amylose (Amyloidosis) Telephone: (33) 42 39 34 43 Fax: (33) 42 39 71 36 Email: [email protected] Web Site: None Background: Association Paulette Ghiron-Bistagne Contre L'Amylose, which translates to 'the Paulette Ghiron-Bistagne Against Amylose (Amyloidosis) Association,' is a voluntary not-for-profit self-help organization that was established in 1994 in France in memory of Paulette, who was affected by a hereditary form of amyloidosis. Amyloidosis is a chronic disorder in which an abnormal starch-like protein complex (amyloid) accumulates in certain tissues and organs of the body. Amyloidosis may occur as a primary disorder for unknown reasons (idiopathic) or may occur secondary to other underlying disorders such as rheumatoid arthritis, familial mediterranean fever, cancer of the bone marrow (i.e., multiple myeloma), or tuberculosis. In addition, some forms of amyloidosis may be inherited. The specific symptoms and findings associated with amyloidosis may vary greatly in range and severity, depending upon which areas of the body are affected. Whereas some affected individuals may have few symptoms, others may experience potentially life-threatening complications. The Association is dedicated to promoting and supporting medical research in the fight against amyloidosis; furthering the knowledge of affected individuals, family members, and health care professionals; working in association with other related organizations; and providing networking opportunities to individuals with amyloidosis and family members. It also provides appropriate referrals to genetic counseling and engages in patient advocacy. In
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addition, it provides a variety of educational materials including brochures in French, English, and Spanish as well as a regular newsletter entitled 'XAIPE.'. •
Back Pain Association of America, Inc Telephone: (410) 255-3633 Fax: (410) 255-7338 Email: [email protected] Background: The Back Pain Association of America, Inc. (BPAA) is a national nonprofit organization dedicated to providing information and support to people who are affected by back and neck pain, their family members, friends, and health care professionals. Established in 1991 and consisting of nearly 4,000 members, BPAA offers programs and information to help affected individuals learn more about their spinal disorders and ways to cope with them. The organization also has a program to help individuals prevent back injuries. BPAA publishes a self-titled quarterly newsletter that helps readers stay informed of updated information and new forms of treatment. The organization s 'Friends Across America' networking program enables affected individuals to exchange information and support via telephone. BPAA also has a physician referral service as well as an information service for physicians who treat back and neck pain. In addition, the Association also promotes research and offers a variety of fact sheets including 'The Relationship Between Nerve Damage and Leg Pain,' 'Urinary Problems and Diseases of the Spine,' 'Arachnoiditis, Questions and Answers,' and 'A Guide to Abdominal and Stretching Exercises.'.
•
Fibromyalgia Association UK Telephone: 01384-820052 Fax: 01384-869467 Email: [email protected] Web Site: http://www.community-care.org.uk/charity/fmauk.html Background: The Fibromyalgia Association UK is an international voluntary organization in the United Kingdom dedicated to providing information, support, and resources to individuals affected by fibromyalgia, a chronic condition characterized by musculoskeletal pain, stiffness, and spasm and associated sleep disturbances. The exact cause of fibromyalgia is unknown. However, the condition appears to develop after certain infections or injuries, for example, or may occur due to or in association with other underlying conditions or disorders, such as rheumatoid arthritis. The Fibromyalgia Association UK provides understandable information on fibromyalgia and promotes networking opportunities that enable affected individuals and family members to exchange mutual support and information. The Association also has a web site on the Internet that discusses the organization's history and mission, provides information on fibromyalgia, and offers linkage to additional support groups, newsgroups, FAQs ('frequently asked questions') on the condition, and related web sites.
•
National Sjogren's Syndrome Association Telephone: Toll-free: (800) 395-6772 Fax: (602) 516-0111
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Email: [email protected] Background: The National Sjogren's Syndrome Association is a voluntary not-for-profit self-help organization dedicated to the identification, control, and cure of Sjogren's Syndrome. Sjogren's Syndrome, a disorder of unknown cause, is characterized by deficient moisture production of the mucous-secreting glands, particularly the tear ducts of the eyes and the salivary glands of the mouth. Associated symptoms and physical abnormalities may include dryness, itching, and burning of the eyes; dryness of the mouth; and, when the lungs are affected, increased susceptibility to repeated respiratory infections. Many affected individuals also experience rheumatoid arthritis. Founded in 1990, the Association provides support to affected individuals and health care professionals worldwide; acts as a resource to those seeking informational materials about the syndrome; promotes and supports research; and sponsors support groups throughout the United States. In addition, the National Sjogren's Syndrome Association engages in patient advocacy; makes appropriate referrals; and conducts regional and national conferences. •
Psoriatic Arthropathy Alliance Telephone: (192) 367-2837 Fax: (192) 367-2837 Email: [email protected] Web Site: http://www.paalliance.org Background: The Psoriatic Arthropathic Alliance (PAA) is a non-profit support and informational organization for individuals affected by psoriatic arthropathy (PA) and other related conditions. Psoriatic arthropathy is a rheumatoid-like arthritic condition that is associated with psoriasis of the skin or nails, and a negative rheumatoid arthritis (RA) serology laboratory test. The disorder is more common in females than males. The mission of the PAA is to provide support and information to individuals affected by PA. Established in 1993, the Alliance also monitors medical and health care services and supports research into the causes, prevention, and management of PA and related conditions. In addition, the group acts as a lobbyist for patient rights. Consisting of 1,000 members, the Alliance produces educational materials that are available to medical professionals, medical students, and the general public. PAA publishes a periodic newsletter and a journal and offers a networking service.
•
Raynaud's and Scleroderma Association (UK) Telephone: 44 (0) 1270 872776 Fax: 44 (0) 1270 883556 Email: [email protected] Web Site: http://www.raynauds.org.uk Background: The Raynaud's and Scleroderma Association (UK) is a voluntary, not-forprofit organization that was established in the United Kingdom in 1982. The Association is dedicated to promoting greater awareness of Raynaud's and scleroderma; offering support, information, and advice to affected individuals and family members; and assisting in the welfare of those who have disabilities resulting from or are chronically ill due to Raynaud's and scleroderma. Raynaud's is a condition characterized by sudden, episodic contraction of the blood vessels supplying the fingers and toes (digits), causing an interruption of blood flow to the digits. Episodes are usually triggered by exposure to
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cold temperatures. If the condition appears to occur spontaneously with no known cause, it is known as Raynaud's disease. When it occurs due to an underlying disorder, such as scleroderma or rheumatoid arthritis, the condition is referred to as Raynaud's phenomenon. Scleroderma is a rare disorder characterized by chronic thickening and hardening of the skin. The disorder may be localized, involving changes of the skin and underlying tissues or may be systemic. •
Sjogren's Syndrome Association, Inc. / Association du Syndrome deSjogren Inc Telephone: (514) 934-3666 Fax: (514) 934-1241 Email: None. Web Site: None Background: Sjogren's Syndrome Association, Inc. (Association du Syndrome de Sjogren, Inc.) is a voluntary not-for-profit health organization in Montreal, Canada dedicated to providing support and education to individuals affected by Sjogren's syndrome, an immunologic disorder characterized by deficient moisture production of the tear duct (lacrimal), salivary, and/or other glands. Associated symptoms typically include abnormal dryness of the eyes (keratoconjunctivitis sicca), the mouth (xerostomia), and other affected glands. The disorder most commonly affects females over the age of 40 and often occurs in association with certain autoimmune, connective tissue disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, or scleroderma). The Sjogren's Syndrome Association was formed in 1994 to provide affected individuals and family members with practical information and coping strategies for living with Sjogren's syndrome. The organization currently has approximately 160 members and a chapter in Ontario, Canada. The Association also gathers and disseminates medical information relating to Sjogren's syndrome, promotes research, and represents the interests all individuals with the disease. In addition, the Sjogren's Syndrome Association conducts regular group meetings and physician conferences, promotes public awareness of the disorder, and offers a variety of educational materials including brochures and a regular newsletter that contains medical news, information on current research, and helpful tips for daily living.
•
Swedish Sjogren's Syndrome Association Telephone: +46 40 97 79 55 Fax: +46 46 30 73 53 Email: [email protected] Web Site: http://www.sjogrensyndrom.se Background: The Swedish Sjogren's Syndrome Association is an international not-forprofit organization dedicated to providing information and support to individuals with Sjogren's Syndrome, family members, and health care professionals. Sjogren's Syndrome, a disorder of unknown cause, is characterized by deficient moisture production of the mucous-secreting glands, particularly the tear ducts of the eyes (lacrimal) and the salivary glands of the mouth. Associated symptoms and physical abnormalities may include abnomal dryness, itching, and burning of the eyes (keratoconjunctivitis sicca); abnormal dryness of the mouth, resulting in cavities, other dental disorders, and loss of odor and taste sensations; and, when the lungs are affected, increased susceptibility to repeated respiratory infections. Many affected individuals
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also experience rheumatoid arthritis. Sjogren's Syndrome, which primarily affects middle-aged women, is thought to be due to an abnormal autoimmune response. Established in 1989, the Swedish Sjogren's Syndrome Association provides networking opportunities that enable affected individuals and family members to exchange information, support, and resources; engages in patient education; and offers a variety of materials including reports and a regular newsletter. The Association also has a web site on the Internet in both English and Swedish that explains the history of Sjogren's Syndrome, discusses current research in Sweden and around the world, provides information concerning the disorder, and offers dynamic linkage to other helpful sources of information on the Internet.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to rheumatoid arthritis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with rheumatoid arthritis. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about rheumatoid arthritis. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “rheumatoid arthritis” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit
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your search to “Organizations” and “rheumatoid arthritis”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “rheumatoid arthritis” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “rheumatoid arthritis” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
23
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
24
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 485
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 487
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on rheumatoid arthritis: •
Basic Guidelines for Rheumatoid Arthritis Felty's syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000445.htm Inflammation of the heart muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000149.htm RA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm Rheumatoid arthritis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000431.htm Vasculitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000874.htm
•
Signs & Symptoms for Rheumatoid Arthritis
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Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Ankle pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003167.htm Bruising Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Elbow pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003172.htm Enlarged liver Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Enlarged lymph nodes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003097.htm Enlarged spleen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003276.htm Eye burning Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003034.htm Eye burning, itching and discharge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003034.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Finger pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003248.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Joint pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Joint swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003262.htm Knee pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003187.htm
Online Glossaries 491
Limited range of motion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003173.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Neck pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003025.htm Nodules Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003230.htm Pale Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003244.htm Paleness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003244.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Skin redness or inflammation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Subcutaneous nodules Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003279.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Swollen glands Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003097.htm Tingling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003206.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Weight gain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003084.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm
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Wrist pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003175.htm •
Diagnostics and Tests for Rheumatoid Arthritis ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm C-reactive protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003356.htm Erythrocyte sedimentation rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Hematocrit Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003646.htm Joint X-rays Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003810.htm Platelet count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003647.htm Rheumatoid factor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003548.htm Sedimentation rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Synovial fluid analysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003629.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm White blood cell count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003643.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm
•
Surgery and Procedures for Rheumatoid Arthritis Hip replacement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002975.htm Splenectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002944.htm
Online Glossaries 493
Total knee Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002974.htm •
Background Topics for Rheumatoid Arthritis Arthritis - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002183.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Prosthesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002286.htm Splints Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000040.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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RHEUMATOID ARTHRITIS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Absenteeism: Chronic absence from work or other duty. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU]
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Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acupuncture Points: Designated locations along nerves or organ meridians for inserting acupuncture needles. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH]
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Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is
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produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an
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adjuvant in bacterins and vaccines, in water purification, etc. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Aminoimidazole Carboxamide: An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
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Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anecdotal report: An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals. [NIH]
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Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Ankylosis: Fixation and immobility of a joint. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between
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antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IgG whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphlogistic: An agent that counteracts inflammation and fever. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antirheumatic Agents: Drugs that are used to treat rheumatoid arthritis. [NIH]
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Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthritis, Adjuvant: An arthritis experimentally induced in animals with Freund's adjuvant. [NIH]
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Arthritis, Psoriatic: Syndrome in which psoriasis is associated with arthritis, often involving inflammation in terminal interphalangeal joints. A rheumatoid factor is not usually present in the sera of affected individuals. [NIH] Arthropathy: Any joint disease. [EU] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Arthus Reaction: A dermal inflammatory reaction produced under conditions of antibody excess, when a second injection of antigen produces intravascular antigen-antibody complexes which bind complement, causing cell clumping, endothelial damage, and vascular necrosis. [NIH] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspartic Endopeptidases: A sub-subclass of endopeptidases that depend on an aspartic acid residue for their activity. EC 3.4.23. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Aurothioglucose: (1-Thio-D-glucopyranosato)gold. A thioglucose derivative used as an antirheumatic and experimentally to produce obesity in animals. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with
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autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Azauridine: A triazine nucleoside used as an antineoplastic antimetabolite. It interferes with pyrimidine biosynthesis thereby preventing formation of cellular nucleic acids. As the triacetate, it is also effective as an antipsoriatic. [NIH] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Back Injuries: General or unspecified injuries to the posterior part of the trunk. It includes injuries to the muscles of the back. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of
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urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow
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cells to grow. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH]
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Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions),
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or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Bursitis: Inflammation of a bursa, occasionally accompanied by a calcific deposit in the underlying supraspinatus tendon; the most common site is the subdeltoid bursa. [EU] Cadherins: A group of functionally related glycoproteins responsible for the calciumdependent cell-to-cell adhesion mechanism. They are divided into subclasses E-, P-, and Ncadherins, which are distinct in immunological specificity and tissue distribution. They promote cell adhesion via a homophilic mechanism. These compounds play a role in the construction of tissues and of the whole animal body. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis
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patients and as a calcium supplement. [NIH] Calcium Pyrophosphate: Diphosphoric acid, calcium salt. An inorganic pyrophosphate which affects calcium metabolism in mammals. Abnormalities in its metabolism occur in some human diseases, notably hypophosphatasia and pseudogout. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capping: A 7-methyl guanosine cap attached to the 5'-end of eucaryotic mRNAs by a phosphodiester linkage. The cap is believed to increase the stability of the message, since most nucleases require a 5'-3'or 3'-5'bond in order to cleave the RNA. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carboxy: Cannabinoid. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH]
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Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH]
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Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Movement: The movement of cells from one location to another. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular adhesion: The close adherence (bonding) to adjoining cell surfaces. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph
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nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemokines, C: Group of chemokines without adjacent cysteines that are chemoattractants for lymphocytes only. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest cavity: Space in body surrounding the lungs. [NIH] Chimera: An individual that contains cell populations derived from different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorambucil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU]
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Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondrosarcoma: A type of cancer that forms in cartilage. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment
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originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Coliphages: Viruses whose host is Escherichia coli. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all
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consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9,
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initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH]
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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corn Oil: Oil from corn or corn plant. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH]
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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate
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internucleotide bonds in DNA duplexes. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystinuria: An inherited abnormality of renal tubular transport of dibasic amino acids leading to massive urinary excretion of cystine, lysine, arginine, and ornithine. [NIH] Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it
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(phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the
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enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatophytosis: Any superficial fungal infection caused by a dermatophyte and involving the stratum corneum of the skin, hair, and nails. The term broadly comprises onychophytosis and the various form of tinea (ringworm), sometimes being used specifically to designate tinea pedis (athlete's foot). Called also epidermomycosis. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dexterity: Ability to move the hands easily and skillfully. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH]
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Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihematoporphyrin Ether: The purified component of hematoporphyrin derivative, it consists of a mixture of oligomeric porphyrins. It is used in photodynamic therapy (hematoporphyrin photoradiation) to treat malignant lesions with visible light and experimentally as an antiviral agent. It is the first drug to be approved in the use of photodynamic therapy in the United States. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilate: Relax; expand. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a
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molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance
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which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
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Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH]
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Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured
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spectrophotometrically or with the naked eye. Many variations of the method have been developed. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermomycosis: An infection caused by dermatophytes. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Infectiosum: Contagious infection with human B19 Parvovirus most commonly seen in school age children and characterized by fever, headache, and rashes of the face,
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trunk, and extremities. It is often confused with rubella. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Etidronate: A drug that belongs to the family of drugs called bisphosphonates. Bisphosphonates are used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Exanthema: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU]
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Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orange-
Dictionary 531
peel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Film Dosimetry: Use of a device (film badge) for measuring exposure of individuals to radiation. It is usually made of metal, plastic, or paper and loaded with one or more pieces of X-ray film. [NIH]
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Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] Flexor: Muscles which flex a joint. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Fluorescein Angiography: Visualization of a vascular system after intravenous injection of a fluorescein solution. The images may be photographed or televised. It is used especially in studying the retinal and uveal vasculature. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in
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diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Follicular Phase: The period of the menstrual cycle that begins with menstruation and ends with ovulation. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental
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conditions, as moulds or yeasts. [EU] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gait: Manner or style of walking. [NIH] Galanthamine: A cholinesterase inhibitor. It has been used to reverse the muscular effects of gallamine and tubocurarine and has been studied as a treatment for Alzheimer's disease and other central nervous system disorders. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
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[NIH]
Gene Conversion: The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action at the level of transcription or translation. These processes include gene activation and genetic induction. [NIH]
Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV
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virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose-6-Phosphate Isomerase: An enzyme that catalyzes the reversible interconversion of glucose 6-phosphate and fructose 6-phosphate, and is a part of the glycolytic and gluconeogenic pathways. Deficiency of the enzyme, an autosomal recessive trait, results in liver glycogenesis and hemolytic anemia. EC 5.3.1.9. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.
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[NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Goiter: Enlargement of the thyroid gland. [NIH] Gold Compounds: Inorganic compounds that contain gold as an integral part of the molecule. [NIH] Gold Sodium Thiomalate: A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis. [NIH]
Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem
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cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanethidine: An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematemesis: The vomiting of blood. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hallux Limitus: A bony proliferation and articular degeneration of the first metatarsophalangeal joint that is characterized by pain and a progressive decrease in the dorsiflexion range of motion. [NIH] Hammer: The largest of the three ossicles of the ear. [NIH] Hand Deformities: Alterations or deviations from normal shape or size which result in a disfigurement of the hand. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH]
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Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH] Hematoporphyrin Derivative: A complex mixture of monomeric and aggregated porphyrins used in the photodynamic therapy of tumors (hematoporphyrin photoradiation). A purified component of this mixture is known as dihematoporphyrin ether. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to
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hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH]
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Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Hobbies: Leisure activities engaged in for pleasure. [NIH] Holmium: An element of the rare earth family of metals. It has the atomic symbol Ho, atomic number 67, and atomic weight 164.93. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hyalin: A clear, homogenous, structureless, eosinophilic substance occurring in pathological degeneration of tissues. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH]
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Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral
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walls of the third ventricle. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH]
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Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Diseases: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated or both. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH]
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In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH]
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Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inosine Monophosphate: Inosine 5'-Monophosphate. A purine nucleotide which has hypoxanthine as the base and one phosphate group esterified to the sugar moiety. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists
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of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-11: Lymphohematopoietic cytokine that has the ability to modulate antigenspecific antibody responses, potentiate megakaryocytes, and regulate bone marrow adipogenesis. [NIH] Interleukin-17: Proinflammatory cytokine produced primarily by T-lymphocytes or their precursors. IL-17 is homologous to an open reading frame found in Herpesvirus saimiri. [NIH]
Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH]
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Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iridocyclitis: Acute or chronic inflammation of the iris and ciliary body characterized by exudates into the anterior chamber, discoloration of the iris, and constricted, sluggish pupil. Symptoms include radiating pain, photophobia, lacrimation, and interference with vision. [NIH]
Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a
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net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Isotope Labeling: Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner synovial membrane. [NIH] Joint Instability: Lack of stability of a joint or joint prosthesis. Factors involved are intraarticular disease and integrity of extra-articular structures such as joint capsule, ligaments, and muscles. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Kininogens: Endogenous peptides present in most body fluids. Certain enzymes convert them to active kinins which are involved in inflammation, blood clotting, complement reactions, etc. Kininogens belong to the cystatin superfamily. They are cysteine proteinase inhibitors. High-molecular-weight kininogen (HMWK) is split by plasma kallikrein to produce bradykinin. low-molecular-weight kininogen (LMWK) is split by tissue kallikrein to produce kallidin. [NIH]
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Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lacrimal: Pertaining to the tears. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leflunomide: An anticancer drug that works by inhibiting a cancer cell growth factor. Also called SU101. [NIH] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
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Leucovorin: The active metabolite of folic acid. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid. [NIH] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH]
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Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a
Dictionary 553
given risk factor. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally
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different populations of cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Magnesium Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH]
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Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment.
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Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metacarpophalangeal Joint: The articulation between a metacarpal bone and a phalanx. [NIH]
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Metalloendopeptidases: Endopeptidases which use a metal, normally zinc, in the catalytic mechanism. This group of enzymes is inactivated by metal chelators. EC 3.4.24. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metatarsophalangeal Joint: The articulation between a metatarsal bone and a phalanx. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Micronuclei: Nuclei, separate from and additional to the main nucleus of a cell, produced during the telophase of mitosis or meiosis by lagging chromosomes or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes. This concept also includes the smaller, reproductive nuclei found in multinucleate protozoans. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by burrowing larvae. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH]
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Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer
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detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]
Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multigene Family: The progeny of a single open-pollinated parent or of a single cross between two individuals. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH]
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Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal Diseases: Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycosis Fungoides: A chronic malignant T-cell lymphoma of the skin. In the late stages the lymph nodes and viscera are affected. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has
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morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Neck Pain: Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Nematode Infections: Infections by nematodes, general or unspecified. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the
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bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in
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the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligopeptides: Peptides composed of between two and twelve amino acids. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as
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codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]
Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but
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from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]
Osteolytic: Causing the breakdown of bone. [NIH] Osteomalacia: A condition marked by softening of the bones (due to impaired mineralization, with excess accumulation of osteoid), with pain, tenderness, muscular weakness, anorexia, and loss of weight, resulting from deficiency of vitamin D and calcium. [EU]
Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteotomy: The surgical cutting of a bone. [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU]
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Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]
Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Parturition: The act or process of given birth to a child. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU]
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Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentostatin: A potent inhibitor of adenosine deaminase. The drug is effective in the treatment of many lymphoproliferative malignancies, particularly hairy-cell leukemia. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity. [NIH]
Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericarditis: Inflammation of the pericardium. [EU]
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Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer
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phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photophobia: Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physicochemical: Pertaining to physics and chemistry. [EU] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilocarpine: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be
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effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective
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tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Poly A: A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually
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accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Postural: Pertaining to posture or position. [EU] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH]
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Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnenolone: Steroid hormone. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH]
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Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of
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prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Proteome: The protein complement of an organism coded for by its genome. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the
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nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychological Adaptation: The alteration of the selective response of a neural unit due to the received signals. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychology, Clinical: The branch of psychology concerned with psychological methods of recognizing and treating behavior disorders. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH]
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Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyelitis: Inflammation of the pelvis of the kidney. It is attended by pain and tenderness in the loins, irritability of the bladder, remittent fever, bloody or purulent urine, diarrhoea, vomiting, and a peculiar pain on flexion of the thigh. [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyridoxal Phosphate: 3-Hydroxy-2-methyl-5-((phosphonooxy)methyl)-4pyridinecarboxaldehyde. An enzyme co-factor vitamin. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons,
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alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioactivity: The quality of emitting or the emission of corpuscular or electromagnetic radiations consequent to nuclear disintegration, a natural property of all chemical elements of atomic number above 83, and possible of induction in all other known elements. [EU] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radium: A radioactive element symbol Ra, atomic number 88, disintegration of uranium and is is used clinically as a source brachytherapy. [NIH]
of the alkaline earth series of metals. It has the atomic and atomic weight 226. Radium is the product of the present in pitchblende and all ores containing uranium. It of beta and gamma-rays in radiotherapy, particularly
Radon: A naturally radioactive element with atomic symbol Rn, atomic number 86, and atomic weight 222. It is a member of the noble gas family and released during the decay of radium and found in soil. There is a link between exposure to radon and lung cancer. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that
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the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU]
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Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which
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contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue
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structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rheumatoid Nodule: Subcutaneous nodules seen in 20-30% of rheumatoid arthritis patients. They may arise anywhere on the body, but are most frequently found over the bony prominences. The nodules are characterized histologically by dense areas of fibrinoid necrosis with basophilic streaks and granules, surrounded by a palisade of cells, mainly fibroblasts and histiocytes. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosomal Proteins: Proteins found in ribosomes. They are believed to have a catalytic function in reconstituting biologically active ribosomal subunits. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Ruminants: A suborder of the order Artiodactyla whose members have the distinguishing feature of a four-chambered stomach. Horns or antlers are usually present, at least in males. [NIH]
Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Saimiri: A genus of the family Cebidae consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH]
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Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scalpel: A small pointed knife with a convex edge. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin.
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Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self Tolerance: The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system. [NIH] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH]
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Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senility: Old age; the physical and mental deterioration associated with old age. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequela: Any lesion or affection following or caused by an attack of disease. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serrated: Having notches or teeth on the edge as a saw has. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Sickness: Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Distribution: The number of males and females in a given population. The distribution may refer to how many men or women or what proportion of either in the group. The
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population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine. [NIH] Sex Factors: Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from sex characteristics, anatomical or physiological manifestations of sex, and from sex distribution, the number of males and females in given circumstances. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH]
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Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Perception: The perceiving of attributes, characteristics, and behaviors of one's associates or social groups. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a
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subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylarthritis: A condition occurring most commonly in children by narrowing of intervertebral disc spaces and some destruction of adjacent vertebrae, followed by slow healing over a period of months. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Standardize: To compare with or conform to a standard; to establish standards. [EU] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH]
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Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Stromelysin 1: An extracellular endopeptidase of vertebrate tissues similar to interstitial collagenase. It digests proteoglycan, fibronectin, collagen types III, IV, V, and IX, and
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activates procollagenase. (Enzyme Nomenclature, 1992) EC 3.4.24.17. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subcapsular: Situated below a capsule. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Sublingual: Located beneath the tongue. [EU] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH]
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Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Suprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathectomy: The removal or interruption of some part of the sympathetic nervous system for therapeutic or research purposes. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]
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Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Cyst: A nodular, tumorlike lesion in or about a tendon sheath or joint capsule, especially of the hands, wrists, or feet. It is not a true cyst as it lacks an epithelial wall, and it does not communicate with the underlying synovial space. The lesion represents a focal accumulation of mucin in the dermis of the dorsal aspect of the distal phalanges or, less often, other portions of the extremities. [NIH] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Synovitis: Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. Synovitis is qualified as fibrinous, gonorrhoeal, hyperplastic, lipomatous, metritic, puerperal, rheumatic, scarlatinal, syphilitic, tuberculous, urethral, etc. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachyphylaxis: 1. Rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. 2. Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telophase: The final phase of cell division, in which two daughter nuclei are formed, the cytoplasm divides, and the chromosomes lose their distinctness and are transformed into chromatin networks. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of
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collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tenosynovitis: Inflammation of a tendon sheath. [EU] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicle: The male gonad where, in adult life, spermatozoa develop; the testis. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH]
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Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Tibia: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]
Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinea Pedis: Dermatological pruritic lesion in the feet, caused by Trichophyton rubrum, T. mentagrophytes, or Epidermophyton floccosum. [NIH] Tinidazole: A nitroimidazole antitrichomonal agent effective against Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia infections. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tissue Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]
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Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tolmetin: An anti-inflammatory antipyretic and analgesic similar in mode of action to indomethacin. It has been proposed as an antirheumatic agent. [NIH] Tome: A zone produced by a number of irregular spaces contained in the outermost layer of denture of the root of a tooth. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonsil: A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the pharynx situated on each side of the fauces, between the anterior and posterior pillars of the soft palate. [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Tophus: A chalky deposit of sodium urate occurring in gout; tophi form most often around joints in cartilage, bone, bursae, and subcutaneous tissue and in the external ear, producing a chronic foreign-body inflammatory response. [EU] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH]
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Traction: The act of pulling. [NIH] Tranexamic Acid: Antifibrinolytic hemostatic used in severe hemorrhage. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triamcinolone Acetonide: An esterified form of triamcinolone. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions.
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[NIH]
Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ulna: The long and medial bone of the forearm. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH]
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Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unsaturated Fats: A type of fat. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vagotomy: The interruption or removal of any part of the vagus (10th cranial) nerve. Vagotomy may be performed for research or for therapeutic purposes. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
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Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertebrobasilar Insufficiency: Localized or diffuse reduction in blood flow through the vertebrobasilar arterial system, which supplies the brain stem; cerebellum; occipital lobe; medial temporal lobe; and thalamus. Characteristic clinical features include syncope; lightheadedness; visual disturbances; and vertigo. brain stem infarctions or other brain infarction may be associated. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH]
600 Rheumatoid Arthritis
Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitamin K: A substance that promotes the clotting of blood. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voluntary Health Agencies: Non-profit organizations concerned with various aspects of health, e.g., education, promotion, treatment, services, etc. [NIH] Walkers: Walking aids generally having two handgrips and four legs. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border
Dictionary 601
of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yin Deficiency: In the yin-yang system of philosophy and medicine, an insufficiency of body fluid (called yinxu), manifesting often as irritability, thirst, constipation, etc. (The Pinyin Chinese-English Dictionary, 1979). [NIH] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
603
INDEX 3 3-dimensional, 339, 495, 575 A Abdomen, 495, 508, 528, 548, 552, 567, 568, 588, 589, 593 Abdominal, 478, 495, 522, 548, 566, 568, 597 Abdominal Pain, 495, 597 Aberrant, 54, 83, 136, 145, 164, 495 Ablation, 125, 495 Abortion, 495, 573 Abscess, 156, 495 Absenteeism, 44, 114, 495 Acceptor, 495, 552, 565, 575 Acculturation, 47, 495 Acetaminophen, 379, 495 Acetylcholine, 495, 513, 514, 529, 562 Acetylcholinesterase, 394, 395, 495 Acetylglucosamine, 12, 495 Acidosis, 495 Actin, 120, 496, 557, 560, 597 Activities of Daily Living, 46, 462, 496 Acupuncture Points, 311, 496 Acute leukemia, 496, 593 Acute renal, 496, 540 Acyl, 358, 359, 371, 381, 496 Adaptability, 328, 419, 496, 512 Adaptation, 56, 328, 496, 559 Adenine, 496, 571, 577 Adenosine, 76, 83, 92, 115, 163, 167, 496, 509, 543, 567, 569 Adenosine Deaminase, 76, 163, 496, 567 Adenovirus, 11, 50, 496 Adenylate Cyclase, 410, 496 Adjunctive Therapy, 94, 496 Adjustment, 156, 308, 329, 496 Adjuvant, 31, 36, 41, 67, 75, 76, 125, 128, 304, 307, 351, 389, 392, 496, 499, 503, 534 Adjuvant Therapy, 307, 496 Adolescence, 463, 496 Adrenal Cortex, 496, 519, 573 Adrenal Glands, 497, 500 Adrenal Medulla, 497, 511, 528, 562 Adrenergic, 401, 497, 528, 538, 574 Adrenergic Agonists, 401, 497 Adverse Effect, 17, 118, 271, 352, 447, 497, 525, 586 Aerobic, 7, 181, 497, 529, 565
Aerobic Exercise, 7, 497 Aetiology, 373, 497 Afferent, 497, 530, 573 Affinity, 13, 42, 64, 73, 86, 99, 103, 122, 178, 369, 380, 401, 497, 552, 554, 574, 587 Agar, 497, 570 Age Groups, 15, 88, 366, 497 Age of Onset, 84, 119, 497 Aged, 80 and Over, 497 Aggravation, 447, 497 Agonist, 497, 560, 569 Airway, 497, 586 Alanine, 130, 408, 497 Albumin, 146, 498, 592 Aldehydes, 413, 498 Alertness, 498, 509 Algorithms, 89, 498, 507 Alimentary, 498, 566, 567 Alkaline, 495, 498, 499, 509, 578 Alkaloid, 305, 406, 407, 498, 515, 559, 597 Alkylating Agents, 498, 513 Alleles, 6, 58, 59, 74, 84, 92, 98, 113, 131, 181, 186, 233, 267, 370, 498, 540, 552 Allergen, 498, 522, 585 Allo, 61, 498 Allogeneic, 60, 278, 363, 498, 537, 539 Alopecia, 498, 520 Alpha Particles, 498, 578 Alpha-helix, 498, 549 Alternative medicine, 445, 498 Aluminum, 381, 395, 396, 498, 601 Aluminum Hydroxide, 381, 395, 396, 498 Alveolar Process, 499, 580 Alveolitis, 262, 499 Ameliorated, 36, 114, 499 Ameliorating, 36, 85, 87, 382, 389, 499 Amine, 499, 541 Amino Acid Sequence, 364, 372, 392, 405, 408, 420, 499, 501, 506, 530, 535 Amino Acid Substitution, 13, 499 Aminoimidazole Carboxamide, 76, 499 Amino-terminal, 10, 499 Ammonia, 496, 499, 536, 591, 598 Amnion, 499 Amniotic Fluid, 378, 499 Amplification, 41, 87, 104, 376, 499 Amygdala, 27, 499, 551 Amyloid, 135, 211, 477, 500
604 Rheumatoid Arthritis
Amyloidosis, 217, 246, 312, 369, 384, 438, 477, 500 Anabolic, 26, 500, 523 Anaemia, 394, 395, 500, 555 Anaerobic, 500, 560, 588 Anaesthesia, 500, 545 Anal, 14, 38, 57, 421, 500, 528, 532, 553, 559 Analog, 8, 13, 90, 278, 352, 500, 514, 543, 558, 574 Analogous, 76, 403, 500, 524, 596 Analytes, 372, 468, 500 Anaphylatoxins, 500, 516 Anaphylaxis, 73, 500 Anaplasia, 500 Anatomical, 27, 138, 500, 513, 526, 544, 584, 586 Androgens, 15, 237, 496, 500, 519 Anecdotal report, 97, 500 Anemia, 175, 180, 346, 433, 490, 501, 509, 533, 536, 539, 559 Anergy, 47, 53, 501, 590 Angina, 501, 562, 574 Angina Pectoris, 501, 574 Angiogenesis, 15, 16, 39, 65, 70, 124, 252, 262, 266, 268, 352, 441, 501, 527, 555 Angiogenesis inhibitor, 16, 501, 527 Anions, 498, 501, 548, 590 Ankle, 21, 185, 238, 381, 395, 396, 397, 426, 472, 490, 501, 599 Ankylosis, 395, 501 Annealing, 501, 571 Anomalies, 501, 593 Anorexia, 380, 387, 404, 501, 565 Antagonism, 383, 428, 501, 509 Anterior chamber, 354, 501, 548 Antibacterial, 501, 514, 588 Antibiotic, 374, 501, 509, 551, 558, 561, 567, 588, 593 Antibody Affinity, 10, 501 Antibody therapy, 8, 149, 216, 228, 502 Antibody-Dependent Cell Cytotoxicity, 502, 549 Anticoagulant, 502, 575 Antidote, 502, 551 Antigen-Antibody Complex, 366, 502, 504, 516 Antigen-presenting cell, 502, 521 Antihypertensive, 502, 538 Anti-Inflammatory Agents, 122, 363, 400, 404, 411, 502, 504, 511, 519 Antimetabolite, 502, 505, 557, 593 Antimicrobial, 438, 502, 522, 524
Antimycotic, 398, 502, 515 Antineoplastic, 369, 498, 499, 502, 505, 519, 520, 534, 557, 566, 567, 586, 593, 600 Antineoplastic Agents, 498, 499, 502, 567, 600 Antioxidant, 135, 214, 215, 222, 294, 296, 502, 504, 565 Antiphlogistic, 400, 502 Antipyretic, 359, 362, 363, 368, 404, 495, 502, 523, 549, 560, 591, 595 Antirheumatic Agents, 256, 502 Antiserum, 503, 505 Antiviral, 503, 523, 529, 534, 546 Anus, 500, 503, 508, 516 Anxiety, 104, 114, 218, 413, 438, 503, 574 Apheresis, 473, 503 Apnea, 503 Apolipoproteins, 503, 552 Applicability, 116, 503 Aqueous, 503, 506, 511, 520, 542, 550 Arachidonate 15-Lipoxygenase, 503, 552 Arachidonate Lipoxygenases, 503, 552 Arachidonic Acid, 42, 70, 293, 371, 503, 520, 525, 543, 551, 574 Arginine, 317, 403, 415, 500, 503, 520, 562, 564, 570, 597 Arterial, 150, 178, 205, 216, 249, 444, 503, 509, 513, 542, 550, 562, 575, 592, 599 Arteries, 503, 508, 518, 553, 557, 560, 571, 594 Arterioles, 503, 508, 510 Arteritis, 229, 281, 346, 503, 572 Artery, 81, 345, 503, 505, 519, 526, 566, 577, 592, 595 Arthritis, Adjuvant, 435, 503 Arthritis, Psoriatic, 180, 351, 436, 504 Arthropathy, 26, 74, 479, 504 Arthroplasty, 13, 153, 158, 161, 221, 224, 268, 433, 504 Arthroscopy, 352, 504 Arthus Reaction, 504, 543 Articulation, 400, 504, 556, 557 Ascorbic Acid, 504, 542 Aseptic, 504, 564, 589 Aspartic, 417, 504, 527 Aspartic Acid, 417, 504 Aspartic Endopeptidases, 504, 527 Aspiration, 187, 351, 504 Aspirin, 6, 19, 30, 317, 359, 362, 363, 365, 368, 385, 398, 401, 405, 472, 504 Assay, 20, 37, 75, 120, 192, 280, 372, 377, 378, 504, 543
Index 605
Asymptomatic, 375, 504 Atrophy, 95, 395, 404, 504 Attenuation, 110, 504, 579 Auditory, 504, 573 Aurothioglucose, 384, 504 Autacoids, 504, 545 Autoantigens, 53, 108, 151, 171, 504 Autologous, 75, 87, 169, 196, 203, 295, 341, 346, 505, 539, 584 Autologous bone marrow transplantation, 87, 505, 539 Autonomic, 27, 495, 505, 562, 568, 591 Autonomic Nervous System, 505, 568, 591 Autopsy, 56, 343, 505 Avidity, 99, 371, 502, 505 Axillary, 505, 508 Axillary Artery, 505, 508 Azauridine, 373, 505 Azotemia, 405, 505 B Back Injuries, 478, 505 Bacteria, 6, 76, 84, 281, 374, 391, 392, 496, 501, 502, 505, 522, 526, 527, 530, 534, 538, 557, 560, 570, 576, 579, 585, 586, 588, 589, 595, 596, 598 Bacterial Infections, 257, 505, 512, 538, 581 Bacterial Physiology, 496, 505 Bacteriophage, 52, 76, 505, 570, 596, 600 Bacteriophage lambda, 52, 505 Bacterium, 505, 540, 595 Bacteriuria, 374, 505 Base, 37, 43, 73, 109, 146, 400, 496, 506, 520, 521, 532, 535, 546, 549, 571, 592 Basement Membrane, 119, 148, 421, 506, 530, 550 Basophils, 506, 538, 551 Behavior Therapy, 116, 506 Benign, 506, 539, 561, 578, 583 Beta-Endorphin, 304, 506 Beta-pleated, 500, 506 Beta-Thromboglobulin, 506, 547 Bilateral, 94, 146, 279, 506 Bile, 506, 527, 534, 541, 552, 589, 592 Bile Acids, 506, 589, 592 Binding Sites, 102, 506 Bioassays, 44, 70, 506 Bioavailability, 419, 506 Bioavailable, 23, 152, 506 Biochemical reactions, 351, 506 Biological Markers, 54, 507 Biological response modifier, 153, 473, 507, 546
Biological therapy, 206, 507, 538 Biomarkers, 54, 55, 71, 149, 507 Biomolecular, 82, 507 Biopsy, 215, 343, 344, 352, 353, 507 Biopsy specimen, 344, 507 Biotechnology, 12, 131, 134, 142, 433, 445, 461, 507 Biotic, 403, 507 Biotransformation, 507, 568 Bladder, 507, 514, 517, 533, 559, 561, 575, 577, 580, 598 Blood Cell Count, 507, 539 Blood Coagulation, 507, 509, 530, 594 Blood Glucose, 507, 540, 546 Blood Platelets, 507, 555, 585, 593 Blood pressure, 150, 345, 375, 379, 438, 490, 502, 508, 510, 542, 558, 587 Blot, 31, 87, 508 Body Fluids, 361, 507, 508, 525, 549, 587, 597 Bone Density, 244, 283, 339, 345, 508 Bone Marrow Transplantation, 87, 169, 468, 508 Bone Resorption, 23, 508 Bone scan, 24, 508, 583 Boron, 139, 286, 508 Boron Neutron Capture Therapy, 139, 508 Bowel, 122, 434, 500, 508, 523, 545, 548, 568, 597 Bowel Movement, 508, 523 Brachial, 22, 345, 508, 555 Brachial Artery, 22, 345, 508 Brachytherapy, 508, 547, 548, 578, 601 Bradykinin, 508, 549, 562 Brain Infarction, 508, 599 Brain Stem, 508, 509, 512, 599 Brain Stem Infarctions, 508, 509, 599 Branch, 89, 487, 509, 544, 553, 564, 567, 568, 576, 577, 587, 591, 593 Breakdown, 126, 379, 389, 412, 509, 523, 534, 564, 565, 584 Broad-spectrum, 95, 509 Bronchi, 398, 509, 528, 595 Bronchial, 12, 434, 509, 541 Bronchitis, 89, 509 Bronchoscopy, 341, 343, 509 Buccal, 348, 509, 553 Bullous, 156, 509, 522 Bupivacaine, 509, 551 Bursitis, 215, 261, 312, 509 C Cadherins, 119, 509
606 Rheumatoid Arthritis
Cadmium, 419, 509 Cadmium Poisoning, 509 Caffeine, 176, 509, 577 Calcium Carbonate, 347, 509 Calcium Pyrophosphate, 407, 510 Calculi, 510, 537 Candidiasis, 438, 510 Candidosis, 510 Capillary, 508, 510, 582, 599 Capillary Fragility, 510, 582 Capping, 12, 510 Capsular, 7, 510 Capsules, 346, 510, 524, 534 Carbohydrate, 510, 519, 536, 572 Carboxy, 129, 510 Carcinogenesis, 510, 513 Carcinogenic, 498, 510, 546, 563, 574, 589 Carcinoma, 58, 220, 305, 510 Cardiac, 21, 29, 99, 132, 185, 197, 247, 419, 509, 510, 526, 528, 534, 551, 560, 589 Cardiology, 21, 221, 510 Cardiorespiratory, 463, 497, 510 Cardioselective, 510, 574 Cardiovascular disease, 19, 22, 28, 99, 132, 299, 363, 510 Carotene, 317, 511, 581 Carpal Tunnel Syndrome, 11, 511 Case report, 49, 147, 151, 201, 260, 271, 276, 283, 511, 514 Case series, 33, 511, 514 Caspase, 111, 511 Catabolism, 63, 100, 511, 598 Catalytic Domain, 129, 511 Cataract, 260, 510, 511 Catecholamine, 166, 511 Cathepsins, 127, 511 Catheter, 340, 353, 511 Cations, 511, 548 Caudal, 511, 523, 542, 572 Causal, 373, 511, 528, 547, 593 Celecoxib, 137, 158, 263, 264, 271, 318, 473, 511 Celiac Disease, 43, 119, 132, 358, 511 Cell Adhesion, 12, 85, 421, 509, 511, 546 Cell Adhesion Molecules, 85, 511 Cell Death, 50, 166, 503, 512, 536 Cell Differentiation, 70, 130, 401, 512, 586 Cell Division, 505, 512, 538, 555, 558, 570, 584, 592 Cell Lineage, 435, 512 Cell membrane, 95, 512, 515, 522, 530, 549, 569
Cell Movement, 85, 512 Cell proliferation, 16, 48, 118, 119, 145, 186, 512, 547, 586 Cell Size, 512, 532 Cell Survival, 49, 122, 512, 538 Cell Transplantation, 346, 468, 512 Cellular adhesion, 65, 512 Cellulose, 512, 533, 570 Central Nervous System Infections, 512, 539 Centrifugation, 374, 512, 539 Ceramide, 111, 512 Cerebellum, 509, 512, 599 Cerebrovascular, 21, 204, 462, 510, 512 Cerebrum, 512 Cervical, 5, 58, 159, 201, 243, 253, 512, 555, 561 Cervix, 495, 513, 532 Character, 367, 501, 513, 521, 536 Chemokines, 28, 30, 49, 65, 70, 96, 159, 200, 389, 419, 513 Chemokines, C, 65, 513 Chemopreventive, 17, 513 Chemotactic Factors, 49, 513, 516 Chemotaxis, 70, 513 Chemotherapeutic agent, 334, 404, 513 Chemotherapy, 196, 197, 319, 496, 513, 583 Chest cavity, 513, 571 Chimera, 122, 513 Chin, 279, 291, 293, 295, 302, 306, 308, 310, 513, 556 Chlorambucil, 401, 513 Chloroquine, 401, 452, 513 Cholecystitis, 145, 513 Cholesterol, 135, 158, 178, 206, 506, 513, 514, 518, 552, 553, 556, 589 Cholesterol Esters, 513, 552 Choline, 379, 495, 513 Cholinergic, 513, 514 Cholinesterase Inhibitors, 394, 514 Chondrocytes, 26, 31, 50, 64, 70, 74, 100, 124, 174, 378, 514, 531 Chondrosarcoma, 100, 514 Choroid, 514, 581, 598 Chromatin, 503, 514, 528, 592 Chromatography, Gel, 86, 514 Chromosomal, 76, 140, 197, 499, 514, 557, 570, 581 Chromosome, 55, 62, 76, 81, 224, 376, 514, 538, 540, 552, 557, 584 Chronic Disease, 51, 85, 105, 106, 112, 362, 363, 380, 425, 476, 514, 516
Index 607
Chylomicrons, 514, 552 Ciliary, 514, 548, 585, 598 Ciliary Body, 514, 548, 585, 598 Circadian, 11, 260, 278, 514 CIS, 100, 514, 544, 581 Cleave, 510, 514 Clindamycin, 374, 514 Clinical Medicine, 514, 572 Clinical Protocols, 105, 514 Clinical study, 311, 334, 514, 518 Clone, 60, 86, 393, 410, 514 Cloning, 24, 63, 87, 100, 136, 330, 413, 507, 515 Clot Retraction, 515, 570 Clotrimazole, 398, 515 Coagulation, 507, 515, 540, 594 Cod Liver Oil, 296, 515 Codon, 269, 408, 515, 535 Cofactor, 515, 575, 594 Cognition, 134, 515 Cognitive behavior therapy, 116, 515 Cognitive restructuring, 515, 589 Cohort Studies, 515, 528 Colchicine, 178, 515, 597 Coliphages, 505, 515 Colitis, 194, 394, 395, 515 Collagen disease, 516, 583 Collagenases, 100, 126, 516 Collapse, 118, 409, 500, 509, 516, 586 Colloidal, 498, 516, 525 Colon, 515, 516, 545, 550, 597 Combination Therapy, 7, 15, 154, 165, 216, 241, 278, 352, 448, 516 Combinatorial, 32, 516 Comorbidity, 35, 150, 516 Complement Activation, 19, 500, 516 Complementary and alternative medicine, 291, 325, 517 Complementary medicine, 291, 308, 517 Complementation, 66, 94, 517 Complete remission, 517, 580 Compliance, 7, 47, 229, 240, 330, 517 Compress, 517, 595 Computational Biology, 461, 517 Computed tomography, 22, 339, 508, 517, 583 Computerized tomography, 517 Conception, 495, 517, 531, 573, 589 Concomitant, 173, 349, 365, 375, 517 Cones, 517, 581 Congestion, 517, 528 Congestive heart failure, 28, 517
Conjugated, 517, 520, 560 Conjunctiva, 517, 545, 549, 583 Connective Tissue Cells, 517, 518 Connective Tissue Diseases, 82, 264, 279, 426, 518 Consciousness, 500, 518, 524, 576, 591 Constipation, 518, 601 Constitutional, 391, 404, 518, 560 Consultation, 83, 163, 518 Consumption, 176, 518, 565 Contracture, 95, 423, 518 Contraindications, ii, 518 Contralateral, 114, 518, 564 Control group, 33, 88, 104, 434, 518 Controlled clinical trial, 32, 97, 105, 176, 219, 302, 518, 579 Controlled study, 151, 152, 216, 225, 297, 302, 334, 518 Conventional therapy, 435, 518 Conventional treatment, 7, 518 Coordination, 38, 512, 518, 559 Corn Oil, 129, 518 Cornea, 501, 518, 537, 549, 583, 598 Corneum, 518, 522, 528 Coronary, 22, 56, 81, 501, 510, 518, 519, 542, 557, 560, 562 Coronary heart disease, 56, 510, 518 Coronary Thrombosis, 519, 557, 560 Corpus, 27, 519, 553, 573, 600 Cortex, 519, 527, 529, 532, 573 Cortical, 215, 519, 529, 573 Corticosteroid, 8, 57, 132, 217, 223, 246, 279, 447, 519, 572, 589 Cortisol, 27, 164, 278, 328, 443, 498, 519 Cortisone, 187, 379, 398, 400, 519, 522, 573 Cranial, 512, 519, 530, 539, 564, 568, 598 Craniocerebral Trauma, 519, 539 Creatine, 286, 297, 519 Creatinine, 519 Criterion, 360, 377, 394, 519 Crossing-over, 519, 579 Cross-Sectional Studies, 519, 528 Cryoglobulinemia, 371, 519 Curative, 97, 237, 519, 562, 593 Cutaneous, 250, 271, 510, 519, 553 Cyanogen Bromide, 66, 519 Cyclic, 138, 148, 170, 245, 496, 509, 520, 538, 562, 572, 574 Cyclooxygenase Inhibitors, 8, 520 Cyclophosphamide, 97, 198, 341, 347, 400, 401, 452, 520 Cyclosporine, 8, 210, 347, 452, 520, 544
608 Rheumatoid Arthritis
Cyst, 192, 520, 592 Cystathionine beta-Synthase, 520, 542 Cysteine Endopeptidases, 520, 527 Cystine, 520 Cystinuria, 384, 520 Cytidine, 381, 520 Cytochrome, 36, 520, 581 Cytochrome b, 520, 581 Cytokine, 5, 10, 13, 15, 24, 28, 31, 37, 40, 41, 43, 48, 53, 59, 60, 62, 65, 66, 70, 75, 77, 82, 84, 86, 91, 94, 95, 96, 99, 101, 104, 105, 111, 115, 118, 122, 123, 128, 129, 136, 142, 183, 196, 197, 198, 206, 209, 218, 245, 263, 274, 278, 352, 389, 400, 401, 413, 415, 419, 434, 435, 436, 444, 448, 520, 531, 547, 586 Cytoplasm, 503, 506, 512, 520, 521, 528, 592 Cytosine, 520, 521, 577 Cytoskeleton, 102, 120, 521, 546, 557 Cytotoxic, 18, 36, 52, 60, 74, 108, 226, 264, 367, 371, 385, 404, 521, 544, 578, 586 Cytotoxicity, 60, 108, 166, 382, 521 D Data Collection, 82, 128, 521, 533 Day Care, 139, 521 De novo, 76, 521 Deamination, 521, 598 Decarboxylation, 521, 541 Decompression, 5, 521 Defense Mechanisms, 521, 546 Degenerative, 26, 68, 127, 173, 379, 412, 521, 540, 564, 582 Dehydration, 118, 438, 521 Dehydroepiandrosterone, 307, 319, 521 Deletion, 42, 60, 80, 83, 97, 99, 103, 121, 130, 503, 521 Delusions, 521, 576 Denaturation, 521, 571 Dendrites, 521, 522, 562 Dendritic, 18, 49, 60, 107, 108, 171, 184, 197, 365, 521, 555 Dendritic cell, 18, 49, 60, 107, 108, 171, 184, 197, 365, 521 Dental Care, 4, 469, 521 Dental Caries, 438, 521 Dentate Gyrus, 522, 541 Dentifrices, 498, 522 Depolarization, 522, 586 Dermatitis, 239, 254, 358, 522 Dermatitis Herpetiformis, 358, 522 Dermatophytosis, 246, 522
Dermis, 66, 522, 557, 591, 592, 596 Desensitization, 59, 73, 522 Detergents, 68, 522, 532 Dexamethasone, 100, 202, 522 Dexterity, 46, 522 Diabetes Mellitus, 98, 259, 275, 522, 536, 540 Diagnostic procedure, 357, 445, 472, 522 Diaphragm, 522, 571 Diarrhea, 118, 522 Diarrhoea, 523, 577 Diastolic, 523, 542 Diathermy, 463, 523 Diclofenac, 173, 271, 319, 523 Diclofenac Sodium, 523 Diencephalon, 523, 542, 573, 593 Digestion, 438, 498, 506, 508, 523, 548, 552, 567, 589 Digestive system, 356, 523, 534 Digestive tract, 523, 587 Dihematoporphyrin Ether, 523, 539 Dihydrotestosterone, 523, 579 Dihydroxy, 523, 582 Dilatation, 495, 523, 573, 599 Dilate, 345, 523 Dilation, 22, 508, 523, 599 Dilator, 523, 562 Diploid, 517, 523, 570 Discrete, 14, 436, 523, 552, 592 Discrimination, 361, 514, 523 Disease Progression, 16, 35, 41, 53, 54, 111, 405, 418, 471, 523 Disease Susceptibility, 45, 58, 69, 73, 523 Dissection, 83, 97, 523 Dissociation, 497, 523 Distal, 248, 265, 415, 524, 576, 592 Diuresis, 509, 524 Dizziness, 51, 524, 599 Dominance, 24, 40, 524 Dorsal, 265, 524, 572, 592 Dosage Forms, 362, 363, 403, 524 Dose-dependent, 50, 524 Double-blind, 19, 117, 118, 152, 178, 218, 219, 225, 233, 282, 297, 311, 334, 336, 352, 524 Double-blinded, 178, 524 Doxycycline, 241, 524 Drive, ii, vi, 10, 20, 23, 84, 277, 416, 424, 524, 551 Drug Design, 76, 454, 524 Drug Interactions, 453, 524 Drug Resistance, 23, 87, 524, 525
Index 609
Drug Tolerance, 401, 524, 525, 595 Drug Toxicity, 34, 374, 525 Duct, 480, 525, 529, 582, 591 Duodenum, 506, 525, 534, 589 Dyes, 500, 506, 525, 533 Dysmenorrhea, 525, 560, 569 Dyspnea, 525, 577 Dystrophy, 358, 525 E Edema, 7, 155, 374, 419, 525, 573 Effector, 15, 18, 47, 83, 86, 123, 130, 136, 495, 502, 516, 525, 549 Effector cell, 86, 123, 502, 525, 549 Effusion, 270, 525, 592 Eicosanoids, 42, 371, 520, 525 Elastic, 7, 525, 536, 587, 595 Elasticity, 249, 525 Elastin, 516, 518, 525, 530 Elective, 257, 525 Electrocardiogram, 345, 525 Electrolyte, 118, 519, 525, 558, 587 Electrophoresis, 142, 222, 360, 525 Embolism, 178, 526 Embolus, 526, 545 Embryo, 495, 499, 512, 526, 545, 573, 588 Embryo Transfer, 526, 573 Emesis, 374, 526 Empiric, 105, 526 Enamel, 522, 526, 549 Encephalitis, 28, 526 Encephalitis, Viral, 526 Encephalomyelitis, 28, 53, 526 Endemic, 213, 526 Endocarditis, 394, 395, 510, 526 Endocardium, 526 Endocrine System, 526, 561 Endocrinology, 43, 131, 176, 202, 526 Endometrium, 526, 556 Endopeptidases, 10, 504, 511, 520, 527, 557, 567, 575, 585 Endostatin, 16, 144, 443, 527 Endothelial cell, 16, 31, 70, 124, 418, 526, 527, 531, 547, 594 Endothelium, 22, 119, 262, 527, 562, 570 Endothelium, Lymphatic, 527 Endothelium, Vascular, 527 Endothelium-derived, 527, 562 Endotoxin, 371, 527, 597 Enhancer, 382, 527 Enkephalin, 506, 527 Enterohepatic, 527, 590 Enterohepatic Circulation, 527, 590
Enteropeptidase, 527, 597 Entorhinal Cortex, 527, 541 Environmental Exposure, 344, 507, 527 Environmental Health, 344, 460, 462, 527 Enzymatic, 396, 499, 509, 511, 516, 522, 527, 541, 556, 571, 581 Enzyme-Linked Immunosorbent Assay, 168, 527 Eosinophilia, 528, 530 Eosinophilic, 528, 530, 541 Eosinophils, 528, 538, 551 Epidemiologic Studies, 14, 507, 528 Epidemiological, 82, 528 Epidermal, 409, 528, 549, 555 Epidermal Growth Factor, 409, 528 Epidermis, 360, 518, 522, 528, 541, 549, 577 Epidermomycosis, 522, 528 Epigastric, 528, 566 Epinephrine, 497, 528, 562, 597 Episcleritis, 528, 583 Epithelial, 119, 361, 514, 528, 540, 550, 592 Epithelial Cells, 528, 540, 550 Epithelium, 119, 360, 506, 527, 528, 534, 548 Epoprostenol, 528, 543 Erythema, 42, 528, 529, 598 Erythema Infectiosum, 528, 529 Erythrocyte Indices, 507, 529 Erythrocytes, 433, 500, 501, 507, 508, 529, 579, 585 Esophageal, 360, 361, 529 Esophagus, 361, 523, 529, 534, 539, 568, 589 Estrogen, 19, 529, 574 Ethidium, 529, 574 Ethnic Groups, 93, 199, 529 Etidronate, 156, 176, 270, 444, 529 Eukaryotic Cells, 529, 544, 564, 597 Evoke, 529, 589 Exanthema, 374, 529 Excitation, 529, 532, 562 Excitatory, 529, 536 Excrete, 529, 580 Exercise Test, 341, 529 Exhaustion, 501, 529 Exocrine, 529, 566 Exocytosis, 108, 530 Exogenous, 40, 56, 366, 382, 386, 389, 400, 411, 507, 526, 530, 535, 575, 597 Exon, 233, 269, 408, 530 Extensor, 95, 256, 265, 530, 576
610 Rheumatoid Arthritis
External-beam radiation, 530, 548, 578, 601 Extracellular Matrix, 10, 29, 120, 126, 127, 129, 517, 518, 530, 531, 546, 555, 565 Extracellular Matrix Proteins, 530, 555 Extracellular Space, 29, 530 Extracorporeal, 380, 530 Extraction, 44, 530 Extremity, 94, 462, 530, 550, 555 Eye Infections, 496, 530 F Facial, 530, 566 Facial Nerve, 530, 566 Factor V, 530, 577 Family Planning, 461, 530 Fasciitis, 230, 530 Fat, 243, 297, 345, 503, 508, 511, 512, 518, 519, 526, 531, 552, 559, 572, 582, 587, 592, 598 Fatigue, 33, 109, 114, 115, 335, 345, 380, 424, 432, 490, 531, 539 Fatty acids, 19, 129, 283, 288, 294, 296, 303, 306, 368, 498, 525, 531, 537, 552, 574, 587 Femur, 531, 594 Fertilization in Vitro, 531, 573 Fetus, 495, 531, 543, 573, 588, 589, 598 Fibril, 20, 531 Fibrillation, 74, 531 Fibrin, 507, 515, 531, 570, 593, 594 Fibrinogen, 171, 531, 570, 593 Fibroblast Growth Factor, 124, 409, 531 Fibrosarcoma, 531 Fibrosis, 74, 338, 341, 343, 434, 438, 518, 531, 577, 583, 584 Fibula, 279, 531, 594 Filgrastim, 346, 531 Film Dosimetry, 182, 531 Filtration, 86, 360, 532 Fine-needle aspiration, 532, 561 Fish Oils, 309, 532 Fissure, 522, 532, 573 Fistula, 532, 534 Fixation, 243, 501, 532, 585 Flatus, 532, 534 Flexion, 95, 532, 577 Flexor, 223, 530, 532 Flow Cytometry, 41, 48, 82, 96, 110, 124, 532 Fludarabine, 352, 532 Fluorescein Angiography, 355, 532 Fluorescence, 85, 361, 389, 529, 532, 533 Fluorescent Dyes, 532, 533
Focus Groups, 34, 533 Folate, 76, 92, 200, 281, 285, 286, 299, 444, 533 Fold, 57, 532, 533 Folic Acid, 76, 92, 284, 285, 286, 300, 301, 339, 351, 533, 551 Follicles, 49, 533 Follicular Phase, 11, 533 Forearm, 188, 508, 531, 533, 555, 597 Free Radicals, 266, 447, 502, 524, 533 Friction, 68, 533, 553 Frontal Lobe, 533, 573 Fructose, 533, 536 Functional magnetic resonance imaging, 5, 533 Fundus, 532, 533 Fungi, 502, 530, 533, 538, 557, 594, 601 Fungus, 510, 533, 560 G Gadolinium, 175, 339, 353, 534 Gait, 95, 534 Galanthamine, 394, 395, 534 Gallbladder, 495, 513, 523, 533, 534 Gamma Rays, 534, 578 Gamma-interferon, 534, 546 Ganglia, 495, 508, 534, 551, 561, 568, 591 Gas, 126, 152, 499, 532, 534, 542, 562, 578, 579, 590, 599 Gastric, 498, 524, 528, 534, 539, 541, 558, 567 Gastric Juices, 534, 567 Gastric Mucosa, 534, 567 Gastrin, 534, 541 Gastroduodenal, 195, 196, 204, 534 Gastroenterology, 43, 131, 233, 534 Gastrointestinal tract, 391, 514, 534, 551, 585, 597 Gelatin, 361, 534, 537, 591, 593 Gelatinase A, 100, 534 Gels, 514, 534 Gene Conversion, 58, 535 Gene Expression, 20, 37, 50, 51, 52, 72, 78, 83, 91, 99, 101, 130, 218, 421, 446, 535 Gene Expression Regulation, 50, 535 Gene Targeting, 102, 535 Gene Therapy, 11, 16, 36, 50, 51, 52, 59, 87, 110, 117, 121, 131, 424, 496, 535 Genetic Code, 535, 563 Genetic Counseling, 477, 535 Genetic Engineering, 80, 376, 507, 515, 535 Genetic Markers, 54, 338, 535 Genetic testing, 535, 571
Index 611
Genotype, 45, 46, 113, 199, 243, 370, 535, 568 Germinal Center, 79, 535 Gestation, 535, 573, 588 Giant Cells, 535, 583 Gland, 220, 439, 496, 497, 519, 536, 553, 555, 566, 570, 575, 584, 589, 590, 591, 594 Glomerular, 148, 536, 580 Glomeruli, 536, 577 Glomerulonephritis, 359, 536, 543, 553 Glomerulus, 536, 561 Glucocorticoid, 83, 174, 182, 193, 221, 227, 250, 280, 446, 522, 536, 572, 573, 596 Glucose, 193, 219, 374, 504, 507, 512, 522, 536, 539, 546, 583 Glucose Intolerance, 522, 536 Glucose-6-Phosphate Isomerase, 219, 536 Glucuronic Acid, 536, 540 Glutamate, 57, 536 Glutamic Acid, 95, 533, 536, 562, 574 Glutamine, 321, 364, 536 Glutathione Peroxidase, 222, 536, 584 Gluten, 193, 278, 288, 292, 511, 536 Glycerol, 536, 537, 569 Glycerophospholipids, 371, 537, 569 Glycine, 82, 364, 499, 537, 562, 585 Glycoprotein, 68, 81, 188, 215, 405, 530, 531, 535, 537, 550, 554, 594, 597 Glycosaminoglycan, 262, 537 Glycosidic, 537, 563 Goats, 28, 537 Goiter, 211, 537 Gold Compounds, 384, 385, 401, 403, 452, 537 Gold Sodium Thiomalate, 384, 537 Gonad, 537, 593 Gonadal, 62, 202, 537, 589 Gout, 122, 240, 366, 404, 412, 416, 425, 477, 515, 537, 560, 595 Governing Board, 537, 572 Grade, 537 Grading, 157, 537 Graft, 85, 117, 145, 346, 387, 438, 537, 541, 544, 560 Graft Rejection, 85, 537, 544 Grafting, 237, 537 Graft-versus-host disease, 537, 560 Gram-negative, 375, 403, 538, 560 Granule, 108, 522, 538 Granulocyte, 414, 531, 538, 547 Granuloma, 70, 538 Granulomatous Disease, Chronic, 538, 581
Grasses, 533, 538 Gravis, 264, 538 Growth factors, 23, 120, 124, 361, 409, 538 Guanethidine, 402, 538 Guanylate Cyclase, 538, 562 H Habitual, 513, 538 Haematemesis, 526, 538 Hair follicles, 522, 538 Half-Life, 380, 395, 538, 543, 569 Hallux Limitus, 233, 538 Hammer, 220, 472, 538, 564 Hand Deformities, 13, 423, 538 Haploid, 538, 570 Haplotypes, 66, 69, 93, 189, 199, 405, 538 Haptens, 497, 539, 585 Headache, 141, 345, 509, 528, 539, 545 Headache Disorders, 539 Health Behavior, 45, 539 Health Promotion, 166, 539 Health Services, 38, 81, 82, 473, 539 Health Status, 3, 4, 9, 32, 88, 112, 159, 171, 189, 215, 251, 266, 276, 340, 345, 462, 539 Heart attack, 510, 539 Heart failure, 539, 577 Heartburn, 313, 379, 539 Hematocrit, 492, 507, 529, 539 Hematopoietic Stem Cell Transplantation, 196, 197, 539 Hematoporphyrin Derivative, 389, 523, 539 Heme, 520, 539, 560, 565, 572 Hemodialysis, 509, 539 Hemoglobin, 501, 507, 529, 539, 540, 550, 572 Hemoglobin A, 540, 572 Hemoglobinopathies, 535, 540 Hemolytic, 346, 433, 531, 536, 540 Hemorrhage, 88, 519, 539, 540, 569, 589, 596 Hemostasis, 5, 540, 546, 585 Heparin, 42, 540 Hepatic, 227, 498, 540 Hepatitis, 157, 196, 246, 366, 398, 444, 540 Hepatocytes, 540 Hereditary, 65, 74, 348, 392, 395, 477, 518, 537, 540 Heredity, 68, 394, 409, 471, 534, 535, 540 Herpes, 60, 373, 540 Herpes Zoster, 540 Herpetiformis, 358, 522, 540 Heterodimers, 540, 546, 596
612 Rheumatoid Arthritis
Heterogeneity, 14, 139, 170, 192, 196, 227, 497, 540 Heterozygote, 98, 540 Hippocampus, 27, 57, 522, 541, 551, 590 Histamine, 275, 386, 452, 500, 541 Histidine, 321, 403, 541 Hobbies, 45, 541 Holmium, 278, 380, 395, 396, 541 Homeostasis, 74, 141, 541 Homodimer, 541, 596 Hormonal, 19, 28, 263, 504, 519, 541 Hormone therapy, 496, 541 Horny layer, 528, 541 Horseradish Peroxidase, 527, 541 Humoral, 29, 115, 240, 386, 434, 537, 541, 544, 594 Humour, 541 Hyalin, 66, 541 Hybrid, 117, 514, 541 Hybridization, 102, 541 Hybridomas, 108, 541, 547 Hydrogen, 495, 499, 506, 510, 521, 530, 536, 542, 552, 558, 562, 563, 565, 568, 576, 590 Hydrogen Peroxide, 536, 542, 552, 590 Hydrolysis, 366, 495, 496, 504, 507, 542, 567, 569, 575, 597 Hydrophilic, 522, 542 Hydrophobic, 502, 522, 537, 542, 552 Hydroxylysine, 516, 542 Hydroxyproline, 364, 499, 516, 542 Hypercalcemia, 529, 542 Hyperglycemia, 387, 414, 542 Hyperhomocysteinemia, 299, 301, 520, 542 Hyperlipidemia, 56, 542 Hyperplasia, 39, 49, 72, 74, 114, 130, 140, 233, 385, 421, 542 Hyperreflexia, 542, 593 Hypersensitivity, 103, 346, 386, 399, 498, 500, 522, 542, 551, 582, 585 Hypertension, 106, 216, 271, 374, 434, 510, 528, 539, 542, 573, 574 Hyperthermia, 523, 542 Hyperthyroidism, 542, 574 Hypertrophy, 385, 542 Hyperuricemia, 537, 542 Hypogonadism, 152, 542 Hypotension, 118, 542 Hypothalamus, 505, 523, 527, 542, 551, 570, 573 Hypoxanthine, 543, 546 Hypoxia, 142, 232, 543
I Ibuprofen, 321, 362, 363, 368, 379, 385, 398, 401, 404, 407, 543, 549, 591 Id, 284, 312, 473, 474, 475, 486, 488, 543 Idiopathic, 25, 83, 204, 235, 279, 343, 477, 543, 583 Iloprost, 278, 543 Imidazole, 399, 499, 515, 541, 543 Immune Complex Diseases, 358, 502, 543 Immune function, 27, 41, 83, 93, 543, 544, 596 Immune Sera, 543 Immune Tolerance, 50, 51, 99, 131, 349, 543 Immunity, 15, 60, 72, 75, 96, 101, 191, 207, 374, 382, 398, 413, 498, 543, 544, 596 Immunization, 13, 24, 40, 41, 48, 51, 60, 75, 78, 368, 389, 391, 543, 544, 573, 585, 592 Immunoassay, 202, 361, 371, 377, 527, 543 Immunocompromised, 77, 543 Immunodeficiency, 28, 76, 386, 543, 544 Immunodeficiency syndrome, 76, 544 Immunogenetics, 45, 199, 544 Immunogenic, 386, 416, 544 Immunoglobulin, 17, 97, 203, 242, 359, 367, 372, 380, 386, 391, 399, 501, 544, 558 Immunohistochemistry, 40, 91, 124, 544 Immunologic, 11, 43, 52, 54, 61, 66, 80, 123, 130, 191, 351, 364, 480, 513, 543, 544, 554, 578 Immunologic Diseases, 543, 544 Immunologic Factors, 351, 544 Immunophilins, 117, 544, 586 Immunosuppressant, 498, 544, 557, 586 Immunosuppressive Agents, 398, 544, 583 Immunosuppressive therapy, 544 Immunotherapy, 8, 24, 41, 45, 53, 66, 507, 522, 544 Immunotoxin, 257, 544 Impairment, 22, 104, 202, 261, 276, 462, 530, 544, 556, 576 Implant radiation, 544, 547, 548, 578, 601 Impotence, 419, 544 In situ, 40, 50, 124, 544 In Situ Hybridization, 40, 124, 544 Incision, 545, 548 Incubated, 366, 545 Incubation, 545, 550 Incubation period, 545, 550 Indicative, 425, 545, 567, 599 Indomethacin, 321, 362, 363, 368, 398, 401, 404, 407, 545, 595
Index 613
Infant, Newborn, 497, 545 Infarction, 132, 508, 545, 571 Infection, 28, 36, 50, 60, 61, 70, 80, 94, 99, 106, 115, 116, 137, 157, 172, 188, 195, 196, 213, 244, 259, 349, 364, 366, 374, 379, 398, 401, 409, 430, 438, 471, 495, 504, 505, 507, 510, 513, 514, 522, 526, 528, 530, 531, 538, 543, 545, 550, 553, 567, 577, 582, 589, 590, 594, 598, 600 Infection Control, 70, 545 Infiltration, 29, 39, 65, 107, 130, 385, 389, 409, 411, 421, 536, 545, 573 Inflammatory bowel disease, 434, 436, 545 Influenza, 60, 99, 185, 545 Informed Consent, 128, 545 Infusion, 27, 144, 156, 339, 340, 546, 596 Ingestion, 279, 509, 546, 571 Inhalation, 363, 546, 571 Initiation, 7, 28, 47, 125, 161, 220, 225, 349, 364, 389, 546, 596 Inlay, 546, 581 Inorganic, 510, 537, 546, 559, 569 Inosine Monophosphate, 76, 546 Insight, 14, 18, 62, 75, 87, 100, 119, 428, 546 Insulator, 546, 559 Insulin, 43, 53, 98, 117, 135, 138, 345, 546, 548 Insulin-dependent diabetes mellitus, 53, 546 Insulin-like, 138, 546 Integrins, 102, 120, 546 Intercellular Adhesion Molecule-1, 214, 546 Interferon, 23, 25, 63, 70, 118, 157, 208, 256, 270, 454, 534, 546 Interferon-alpha, 157, 270, 546 Interleukin-1, 115, 138, 140, 147, 150, 190, 209, 218, 237, 266, 409, 413, 414, 454, 546, 547 Interleukin-10, 150, 190, 209, 547 Interleukin-11, 140, 547 Interleukin-17, 138, 209, 413, 547 Interleukin-2, 209, 269, 330, 547 Interleukin-4, 190, 232, 402, 547 Interleukin-6, 69, 149, 173, 307, 388, 409, 414, 547 Interleukin-8, 409, 419, 547 Interleukins, 234, 544, 547 Intermittent, 10, 156, 176, 447, 547 Internal radiation, 547, 548, 578, 601 Interstitial, 29, 31, 54, 101, 118, 508, 530, 534, 547, 548, 561, 580, 589, 601
Interstitial Collagenase, 101, 534, 547, 589 Intervention Studies, 106, 547 Intervertebral, 462, 547, 588 Intestinal, 228, 234, 281, 378, 511, 527, 547, 554 Intestinal Mucosa, 511, 547 Intestine, 508, 527, 548, 550 Intoxication, 548, 601 Intramuscular, 8, 25, 226, 261, 282, 548, 566, 596 Intramuscular injection, 25, 548 Intraperitoneal, 95, 548 Intravenous, 27, 97, 210, 241, 334, 406, 454, 532, 546, 548, 566 Intrinsic, 497, 506, 548 Invasive, 17, 20, 21, 74, 77, 100, 113, 135, 253, 376, 388, 393, 543, 548, 554 Involuntary, 531, 548, 560, 587 Ionizing, 498, 527, 548, 578 Ions, 366, 506, 524, 525, 542, 548 Iridocyclitis, 6, 279, 548 Iris, 501, 518, 548, 577, 598 Irradiation, 341, 347, 508, 548, 601 Ischemia, 501, 504, 548 Islet, 43, 98, 548 Isoenzymes, 163, 548 Isomerases, 544, 548 Isopropyl, 417, 548 Isotonic, 7, 548 Isotope Labeling, 116, 549 J Joint Capsule, 77, 411, 549, 592 Joint Instability, 423, 549 K Kallidin, 508, 549 Kb, 77, 460, 549 Keratin, 170, 549 Keratinocytes, 547, 549 Keratitis, 54, 549 Keratoconjunctivitis, 480, 549, 586 Keratoconjunctivitis Sicca, 480, 549, 586 Keratolytic, 522, 549 Ketoprofen, 321, 407, 549 Killer Cells, 230, 549 Kinetic, 59, 79, 548, 549 Kininogens, 212, 549 L Labile, 516, 530, 550 Laceration, 550, 593 Lacrimal, 480, 530, 549, 550, 586 Lactation, 550, 574 Lag, 47, 550
614 Rheumatoid Arthritis
Laminin, 361, 506, 530, 550 Large Intestine, 523, 548, 550, 579, 587 Latency, 129, 550 Latent, 361, 550, 572 Lavage, 8, 177, 550 Least-Squares Analysis, 550, 580 Lectin, 184, 273, 550, 556 Leflunomide, 5, 117, 146, 148, 149, 164, 213, 214, 252, 261, 265, 274, 295, 300, 302, 335, 424, 443, 452, 473, 550 Leg Ulcer, 178, 550 Lens, 510, 511, 550, 580, 600 Lentivirus, 28, 550 Leprosy, 245, 403, 550 Lethal, 102, 214, 384, 550 Leucine, 506, 550, 567 Leucocyte, 359, 550 Leucovorin, 9, 551 Leukapheresis, 503, 551 Leukemia, 218, 249, 358, 369, 535, 551, 567 Leukocytes, 29, 30, 39, 41, 85, 102, 303, 389, 506, 507, 508, 513, 528, 545, 546, 547, 551, 597 Leukocytosis, 391, 551 Leukotrienes, 73, 170, 392, 503, 525, 551 Libido, 500, 551 Library Services, 486, 551 Lidocaine, 181, 551 Life Expectancy, 22, 28, 551 Ligaments, 385, 412, 518, 549, 551, 560 Ligands, 12, 100, 123, 130, 260, 304, 372, 410, 511, 546, 551 Ligation, 207, 551 Likelihood Functions, 551, 580 Limbic, 499, 551, 573 Limbic System, 499, 551, 573 Lincomycin, 514, 551 Linear Models, 552, 580 Linkage, 56, 58, 119, 129, 140, 224, 275, 370, 448, 478, 481, 510, 535, 552 Linkage Disequilibrium, 56, 58, 119, 370, 552 Lip, 438, 552 Lipid, 22, 30, 41, 215, 297, 374, 442, 503, 513, 536, 546, 552, 559, 565 Lipid Peroxidation, 22, 552, 565 Lipophilic, 121, 552 Lipopolysaccharide, 264, 538, 552 Lipoprotein, 42, 77, 81, 135, 206, 538, 552, 553, 600 Liposomes, 139, 552 Lipoxygenase, 42, 365, 503, 551, 552
Liver, 5, 78, 126, 215, 216, 379, 405, 490, 495, 498, 499, 500, 503, 506, 513, 520, 523, 527, 532, 533, 534, 536, 540, 552, 573, 583, 598 Liver scan, 552, 583 Localization, 18, 27, 49, 72, 120, 215, 270, 389, 544, 552 Locomotion, 552, 570 Locomotor, 362, 363, 368, 552 Logistic Models, 552, 580 Longitudinal study, 43, 143, 194, 214, 236, 553 Low-density lipoprotein, 178, 552, 553 Lubricants, 553 Lubrication, 68, 74, 438, 553 Lucida, 550, 553 Lumbar, 248, 553 Lung Transplantation, 343, 553 Lupus Nephritis, 43, 553 Lutein Cells, 553, 574 Lymph, 5, 13, 78, 95, 391, 395, 397, 398, 490, 505, 512, 527, 541, 553, 560, 583, 585, 590 Lymph node, 5, 13, 78, 95, 397, 490, 505, 513, 553, 560, 583 Lymphadenopathy, 391, 395, 398, 553, 585 Lymphatic, 527, 545, 553, 556, 587, 588, 594 Lymphatic system, 553, 587, 588, 594 Lymphocyte Subsets, 109, 263, 553 Lymphoid, 49, 78, 101, 347, 365, 372, 392, 501, 535, 550, 554, 595 Lymphokine, 412, 419, 554 Lymphoma, 49, 137, 220, 249, 251, 253, 554, 560 Lymphopenia, 228, 554 Lymphoproliferative, 218, 554, 567 Lysine, 403, 520, 542, 554, 597 Lytic, 554, 585, 600 M Macrophage Activation, 52, 229, 554 Macrophage Colony-Stimulating Factor, 414, 554 Magnesium Salicylate, 379, 554 Major Histocompatibility Complex, 6, 14, 24, 48, 56, 73, 122, 202, 418, 446, 448, 538, 547, 554 Malabsorption, 511, 554 Malignancy, 119, 554 Malignant, 255, 369, 398, 502, 523, 531, 554, 559, 560, 561, 578, 583 Malignant tumor, 369, 554, 559
Index 615
Malnutrition, 498, 504, 554 Mammary, 554, 555 Mandible, 499, 513, 554, 580 Manic, 555, 576 Manic-depressive psychosis, 555, 576 Manifest, 103, 555 Mastitis, 28, 555 Maximum Tolerated Dose, 525, 555 Measles Virus, 386, 555 Medial, 555, 564, 594, 597, 599 Median Nerve, 511, 555 Mediate, 14, 51, 60, 64, 69, 70, 73, 86, 99, 111, 119, 120, 230, 401, 511, 549, 555 Mediator, 98, 122, 124, 268, 304, 345, 547, 555, 585 Medical Records, 19, 32, 335, 344, 348, 555 Medical Staff, 524, 555 Medicament, 400, 555, 591 MEDLINE, 4, 461, 555 Megakaryocytes, 547, 555, 594 Megaloblastic, 533, 555 Meiosis, 555, 557, 559, 591 Melanin, 548, 555, 569, 597 Melanocytes, 555 Melanoma, 183, 508, 555 Membrane Lipids, 556, 569 Membrane Proteins, 552, 556 Memory, 33, 57, 96, 99, 123, 136, 411, 477, 501, 535, 556 Menarche, 146, 556 Meninges, 512, 519, 556 Menopause, 19, 556, 572, 573, 574 Menstrual Cycle, 11, 93, 533, 556, 573 Menstruation, 525, 533, 556 Mental Disorders, 356, 556, 569, 573, 576 Mental Health, iv, 9, 44, 116, 356, 460, 464, 556, 573, 577 Mental Processes, 524, 556, 576 Mercury, 532, 556 Mesenchymal, 528, 554, 556 Meta-Analysis, 38, 113, 304, 556 Metabolic disorder, 537, 556 Metabolite, 384, 499, 507, 551, 556, 573 Metacarpophalangeal Joint, 13, 162, 237, 255, 273, 556 Metalloendopeptidases, 527, 557 Metastasis, 95, 511, 555, 557 Metastatic, 23, 95, 557, 584 Metatarsophalangeal Joint, 221, 538, 557 Methionine, 93, 364, 506, 557, 590 Methyltransferase, 93, 211, 557
MI, 12, 28, 33, 56, 59, 65, 120, 130, 142, 188, 294, 381, 391, 493, 557 Mice Minute Virus, 557, 566 Microbe, 557, 595 Microbiology, 67, 93, 496, 506, 557 Microfilaments, 407, 557 Micronuclei, 192, 280, 557 Microorganism, 515, 557, 566, 600 Micro-organism, 522, 557, 569 Microscopy, 73, 85, 120, 374, 506, 541, 557 Microspheres, 125, 557 Microtubules, 407, 557, 566 Migrans, 42, 557 Milligram, 383, 558 Milliliter, 508, 558 Millimeter, 311, 558 Mineralization, 558, 565 Mineralocorticoids, 496, 519, 558 Minocycline, 8, 214, 558 Miotic, 558, 569 Misoprostol, 90, 349, 558 Mitosis, 503, 557, 558 Mitotic, 406, 558, 599 Mobility, 7, 17, 45, 95, 197, 360, 385, 424, 462, 558 Mobilization, 283, 346, 558 Modeling, 39, 79, 227, 448, 524, 558 Modification, 7, 70, 74, 83, 84, 382, 401, 499, 535, 558, 577 Modulator, 36, 410, 558 Monitor, 43, 59, 72, 80, 245, 519, 558, 563 Monoclonal antibodies, 21, 40, 60, 130, 215, 309, 361, 372, 377, 378, 415, 434, 558, 582 Monocyte, 119, 283, 419, 502, 554, 559 Mononuclear, 39, 51, 102, 121, 188, 228, 241, 245, 363, 385, 531, 538, 554, 559, 597 Monotherapy, 128, 165, 174, 216, 218, 435, 559 Mood Disorders, 57, 559 Morbillivirus, 555, 559 Morphine, 402, 559, 561, 564 Morphology, 120, 511, 554, 559 Motility, 383, 545, 559, 585 Motion Sickness, 559, 561 Mucins, 12, 559, 582 Mucosa, 534, 553, 559, 574, 589 Mucus, 559, 597 Multicenter study, 29, 89, 559 Multidrug resistance, 163, 559 Multigene Family, 129, 559 Multiple Myeloma, 23, 477, 559
616 Rheumatoid Arthritis
Multiple sclerosis, 43, 51, 52, 115, 143, 208, 373, 381, 411, 559 Multivalent, 505, 559 Multivariate Analysis, 35, 559 Muscle tension, 424, 559 Muscular Dystrophies, 525, 560 Musculoskeletal Diseases, 18, 81, 82, 92, 560 Myalgia, 545, 560 Myasthenia, 264, 560 Mycophenolate mofetil, 131, 560 Mycoplasma, 76, 84, 512, 560 Mycosis, 373, 560 Mycosis Fungoides, 373, 560 Mydriatic, 523, 560 Myelin, 53, 559, 560 Myeloid Cells, 30, 415, 560 Myeloma, 23, 560 Myocardial infarction, 28, 132, 506, 519, 557, 560, 574 Myocarditis, 99, 394, 395, 560 Myocardium, 501, 557, 560 Myoglobin, 560, 572 Myopathy, 260, 560 Myosin, 560, 597 Myositis, 143, 237, 344, 560 N Naive, 47, 67, 78, 137, 560 Naloxone, 506, 560 Naproxen, 204, 219, 287, 362, 363, 368, 385, 398, 401, 404, 560 Narcolepsy, 119, 560 Narcotic, 559, 560 Nasal Mucosa, 545, 561 Nasopharynx, 398, 561 Nausea, 118, 374, 524, 561, 598 NCI, 1, 356, 366, 459, 514, 561 Neck Pain, 5, 478, 561 Needle biopsy, 351, 532, 561 Nematode Infections, 37, 561 Neomycin, 67, 561 Neoplasia, 126, 561 Neoplasm, 561, 583, 597 Neoplastic, 49, 97, 387, 389, 406, 500, 541, 554, 561, 563, 583 Nephritis, 118, 561 Nephrology, 43, 131, 561 Nephropathy, 411, 561 Nerve Endings, 538, 561 Nervous System, 42, 54, 211, 373, 401, 411, 495, 497, 498, 505, 509, 512, 514, 534,
536, 551, 555, 559, 561, 562, 564, 568, 585, 591 Networks, 35, 63, 66, 561, 592 Neural, 5, 35, 115, 438, 497, 500, 541, 561, 576 Neuroendocrine, 11, 95, 382, 561 Neurogenic, 114, 561 Neurologic, 5, 562 Neurology, 21, 43, 47, 253, 562 Neuromuscular, 94, 495, 562, 597 Neuromuscular Junction, 495, 562 Neurons, 521, 522, 529, 534, 561, 562, 591 Neuropsychological Tests, 33, 562 Neurotransmitter, 495, 496, 499, 504, 508, 514, 536, 537, 541, 562, 586, 590 Neutralization, 49, 562 Neutrons, 498, 508, 548, 562, 577, 578 Neutrophil, 30, 72, 167, 183, 231, 419, 546, 562 Niacin, 284, 285, 562, 597 Nitric Oxide, 26, 62, 191, 205, 446, 562 Nitrogen, 15, 498, 499, 500, 520, 530, 532, 536, 562, 597 Nitroglycerin, 345, 562 Norepinephrine, 234, 497, 538, 562 Nuclear, 30, 119, 182, 197, 203, 299, 341, 529, 534, 535, 551, 563, 578, 593 Nuclear Medicine, 203, 299, 341, 563 Nuclei, 498, 499, 535, 551, 554, 557, 558, 562, 563, 564, 576, 592 Nucleic acid, 387, 402, 408, 505, 521, 529, 535, 541, 543, 544, 562, 563, 577 Nucleic Acid Hybridization, 541, 563 Nucleus, 503, 505, 506, 514, 520, 528, 529, 534, 555, 557, 559, 562, 563, 573, 576, 589 O Observational study, 159, 563 Occipital Lobe, 563, 599 Ocular, 267, 274, 436, 563 Odds Ratio, 563, 580 Ointments, 524, 563, 587 Oligopeptides, 74, 563 Oligosaccharides, 62, 563 Oncogenic, 546, 550, 563, 576 Oncolysis, 563 Oncolytic, 406, 563 Opacity, 511, 521, 563 Open Reading Frames, 550, 563 Ophthalmic, 354, 564 Ophthalmologic, 474, 564 Ophthalmology, 229, 238, 262, 279, 281, 532, 564
Index 617
Opiate, 506, 527, 559, 560, 564 Opium, 559, 564 Opsin, 564, 581, 582 Optic Chiasm, 542, 564, 573 Optic Nerve, 564, 581, 583 Oral Health, 4, 92, 564 Oral Hygiene, 5, 564 Oral Manifestations, 5, 564 Orbit, 564 Orbital, 143, 237, 564 Organ Culture, 95, 110, 564 Organelles, 512, 520, 555, 564 Ornithine, 520, 564 Ossicles, 538, 564 Osteoblasts, 15, 70, 86, 565 Osteoclasts, 90, 127, 565 Osteolysis, 103, 565 Osteolytic, 23, 565 Osteomalacia, 305, 565 Osteoporosis, 15, 82, 86, 221, 237, 246, 248, 281, 313, 443, 447, 463, 565 Osteotomy, 269, 565 Outpatient, 8, 272, 565 Ovary, 537, 565, 589 Overall survival, 49, 565 Ovulation, 533, 565 Ovum, 535, 565, 573, 574 Oxidation, 495, 502, 503, 507, 520, 536, 552, 565 Oxidative metabolism, 551, 565 Oxidative Stress, 22, 135, 294, 565 Oxygen Consumption, 529, 565, 581 Oxygenase, 242, 365, 565 Oxygenation, 88, 565 Oxytocic, 558, 566 P Paclitaxel, 279, 297, 334, 566 Palate, 561, 566, 595 Palliative, 367, 566, 593 Palsy, 201, 566 Pancreas, 126, 495, 507, 523, 534, 546, 548, 566, 597 Pancreatic, 89, 95, 566 Parasite, 566 Parasitic, 416, 566 Parasitic Diseases, 416, 566 Parenteral, 216, 250, 282, 386, 407, 566 Parietal, 566, 568, 571 Parotid, 220, 566, 583 Partial remission, 566, 580 Partial response, 350, 566 Partnership Practice, 566, 573
Parturition, 566, 574 Parvovirus, 138, 239, 528, 557, 566 Patch, 566, 596 Pathogen, 28, 545, 566 Pathogenesis, 11, 19, 20, 22, 23, 25, 28, 39, 40, 42, 49, 52, 57, 62, 63, 67, 68, 69, 72, 73, 77, 80, 82, 83, 84, 90, 91, 96, 100, 103, 104, 107, 124, 134, 138, 141, 165, 197, 202, 237, 239, 266, 281, 366, 371, 376, 405, 410, 419, 430, 435, 567 Pathologic, 16, 57, 86, 240, 248, 400, 403, 448, 495, 503, 507, 510, 518, 542, 567, 576, 580, 599 Pathologic Processes, 16, 503, 567 Pathologies, 115, 127, 387, 567 Pathophysiology, 4, 15, 40, 42, 73, 82, 255, 434, 567 Patient Advocacy, 477, 479, 567 Patient Education, 112, 304, 352, 471, 481, 484, 486, 493, 567 Pelvis, 462, 495, 553, 567, 577, 598 Penicillamine, 5, 322, 359, 384, 385, 390, 398, 400, 401, 404, 425, 452, 567 Penicillin, 384, 501, 567, 598 Pentostatin, 365, 567 Pepsin, 558, 567 Pepsin A, 567 Peptic, 434, 567 Peptic Ulcer, 434, 567 Peptide Fragments, 360, 405, 567 Peptide Hydrolases, 527, 567 Perception, 307, 567, 583 Perennial, 567, 596 Perfusion, 380, 543, 567, 594 Pericarditis, 54, 74, 221, 404, 567 Pericardium, 567, 568, 592 Periodontal disease, 92, 200, 568 Peripheral Nervous System, 562, 566, 568, 590 Peritoneal, 241, 358, 548, 568 Peritoneal Cavity, 548, 568 Peritoneum, 568 PH, 135, 140, 195, 219, 508, 568 Phagocyte, 406, 554, 568 Phantom, 211, 568 Pharmaceutical Preparations, 362, 512, 534, 568 Pharmaceutical Solutions, 524, 568 Pharmacogenetics, 171, 275, 568 Pharmacokinetic, 243, 568 Pharmacologic, 26, 27, 35, 57, 115, 122, 401, 436, 504, 538, 568, 594, 595
618 Rheumatoid Arthritis
Pharynx, 545, 561, 568, 595 Phenotype, 18, 45, 54, 63, 77, 80, 96, 102, 128, 230, 507, 517, 568 Phenyl, 358, 398, 417, 569 Phenylalanine, 322, 323, 567, 569, 597 Phosphates, 374, 569 Phospholipases, 569, 586 Phospholipids, 283, 531, 552, 556, 569 Phosphorus, 509, 569 Phosphorylated, 102, 110, 569 Phosphorylation, 69, 73, 116, 229, 569 Photodynamic therapy, 388, 523, 539, 569 Photophobia, 548, 569 Physical Examination, 6, 335, 337, 340, 344, 353, 355, 436, 463, 472, 473, 569 Physical Fitness, 442, 569 Physical Therapy, 94, 233, 362, 363, 368, 463, 472, 569 Physicochemical, 360, 569 Physiologic, 11, 26, 63, 70, 95, 116, 405, 463, 497, 538, 549, 556, 569, 574, 579, 580 Physiology, 109, 174, 366, 438, 507, 510, 526, 534, 561, 569 Pigments, 511, 569, 581 Pilocarpine, 438, 439, 569 Pilot study, 25, 78, 233, 354, 569 Piroxicam, 323, 329, 404, 569 Pituitary Gland, 216, 234, 419, 519, 531, 570 Plana, 570, 585 Plants, 282, 498, 504, 513, 536, 550, 559, 563, 569, 570, 572, 582, 583, 595, 596 Plaque, 29, 570 Plasma cells, 69, 365, 415, 501, 559, 560, 570 Plasma Kallikrein, 549, 570 Plasmapheresis, 347, 503, 570 Plasmid, 66, 402, 570, 599 Plasmin, 233, 570 Plasminogen, 10, 570 Plasminogen Activators, 570 Platelet Activation, 570, 586 Platelet Aggregation, 500, 528, 543, 562, 570, 594 Platelet Count, 118, 570 Platelet-Derived Growth Factor, 409, 570 Plateletpheresis, 503, 571 Platelets, 506, 562, 570, 571, 594 Pleated, 549, 571 Pleura, 571 Pleural, 282, 407, 571 Pleural cavity, 407, 571
Pleural Effusion, 282, 571 Pneumonia, 118, 518, 571 Pneumonitis, 161, 225, 509, 571 Point Mutation, 17, 571 Poisoning, 384, 509, 525, 548, 556, 561, 571, 585 Poly A, 48, 389, 571 Polyarteritis Nodosa, 346, 543, 571 Polyarthritis, 36, 75, 76, 158, 369, 380, 403, 446, 549, 571, 586 Polymerase, 20, 61, 144, 152, 180, 571 Polymerase Chain Reaction, 20, 61, 152, 180, 571 Polymorphic, 74, 514, 522, 571 Polymorphism, 47, 58, 100, 105, 143, 150, 153, 185, 191, 208, 211, 242, 264, 268, 269, 571 Polymyalgia Rheumatica, 202, 240, 571 Polysaccharide, 502, 512, 537, 572, 575 Polyunsaturated fat, 129, 572, 594 Porphyrins, 389, 523, 539, 572 Posterior, 5, 243, 305, 447, 500, 505, 512, 514, 524, 548, 561, 563, 566, 572, 583, 595 Postmenopausal, 19, 160, 188, 248, 329, 443, 565, 572 Postnatal, 65, 572, 589 Postoperative, 569, 572 Postsynaptic, 572, 586 Post-translational, 70, 74, 572 Postural, 274, 572 Potentiate, 547, 572 Potentiation, 514, 572, 586 Practice Guidelines, 464, 473, 572 Precancerous, 513, 572 Precipitation, 360, 572 Preclinical, 23, 128, 435, 572 Precursor, 74, 503, 513, 520, 525, 527, 562, 569, 570, 572, 573, 596, 597, 598 Predisposition, 55, 58, 66, 139, 370, 385, 400, 572 Prednisolone, 117, 139, 447, 572, 573 Prednisone, 193, 219, 232, 283, 335, 337, 339, 349, 355, 379, 446, 447, 573 Pre-Eclampsia, 115, 506, 573 Prefrontal Cortex, 27, 573 Pregnancy Outcome, 267, 573 Pregnenolone, 258, 323, 573 Premenopausal, 11, 152, 164, 283, 344, 345, 573 Prenatal, 390, 526, 573 Preoperative, 5, 573 Preoptic Area, 115, 573
Index 619
Primary Prevention, 19, 98, 573 Private Practice, 162, 573 Probe, 58, 573 Procaine, 551, 573 Prodrug, 89, 573 Progeny, 387, 414, 559, 573 Progesterone, 573, 574, 589 Prognostic factor, 149, 247, 573, 591 Progressive disease, 12, 105, 404, 574 Projection, 521, 562, 564, 573, 574 Prolactin, 382, 574 Proline, 364, 417, 516, 542, 574 Promoter, 12, 90, 100, 144, 150, 164, 191, 233, 242, 264, 574 Prophylaxis, 368, 373, 385, 394, 411, 574, 598 Propidium, 110, 574 Proportional, 527, 566, 574 Propranolol, 402, 574 Prospective study, 131, 133, 144, 158, 220, 224, 254, 279, 553, 574 Prostaglandin, 26, 141, 257, 280, 281, 410, 413, 435, 520, 528, 558, 574, 591, 594 Prostaglandin-Endoperoxide Synthase, 520, 574 Prostaglandins A, 545, 574, 575 Prostate, 507, 575, 597 Prosthesis, 226, 493, 549, 575 Protease, 71, 108, 516, 575 Protease Inhibitors, 71, 575 Protein Binding, 575, 594 Protein Conformation, 499, 549, 575 Protein Kinases, 69, 575 Protein S, 370, 377, 394, 433, 507, 535, 561, 575, 593 Proteinuria, 559, 573, 575 Proteoglycan, 24, 29, 40, 42, 71, 74, 126, 362, 435, 575, 589 Proteolytic, 31, 80, 323, 366, 516, 527, 531, 570, 575 Proteome, 149, 222, 575 Protocol, 5, 8, 25, 41, 48, 53, 59, 75, 95, 117, 118, 349, 351, 575 Protons, 498, 542, 548, 575, 577 Proto-Oncogene Proteins, 566, 576 Proto-Oncogene Proteins c-mos, 566, 576 Protozoa, 557, 576 Protozoal, 398, 576 Proximal, 65, 146, 439, 524, 571, 576 Pruritic, 522, 576, 594 Psoriasis, 60, 373, 479, 504, 576 Psychiatric, 35, 337, 507, 556, 576, 587
Psychiatry, 33, 35, 36, 57, 109, 279, 532, 576 Psychic, 551, 556, 576 Psychoactive, 576, 601 Psychological Adaptation, 25, 576 Psychology, 33, 109, 115, 133, 156, 161, 176, 207, 246, 302, 428, 524, 576 Psychology, Clinical, 109, 576 Psychosis, 462, 576 Psychotherapy, 515, 576 Public Health, 18, 35, 44, 92, 112, 268, 464, 577 Public Policy, 461, 577 Pulmonary, 43, 131, 159, 282, 305, 338, 341, 343, 508, 518, 528, 529, 551, 577, 599 Pulmonary Artery, 508, 577, 599 Pulmonary Fibrosis, 338, 341, 343, 577 Pulse, 97, 150, 558, 577 Punishment, 27, 577 Pupil, 518, 523, 548, 558, 560, 577 Purifying, 376, 522, 577 Purines, 577, 585 Purulent, 495, 577, 598 Pustular, 540, 577 Pyelitis, 398, 577 Pyelonephritis, 375, 577 Pyridoxal, 242, 373, 520, 577 Pyridoxal Phosphate, 373, 520, 577 Pyrimidines, 577, 585 R Race, 11, 93, 462, 557, 577 Radiation, 126, 437, 438, 495, 496, 501, 527, 530, 531, 532, 533, 534, 542, 543, 547, 548, 568, 577, 578, 583, 601 Radiation therapy, 437, 438, 495, 496, 530, 547, 548, 578, 583, 601 Radio Waves, 523, 578 Radioactivity, 126, 578 Radiography, 5, 35, 221, 463, 578 Radioimmunotherapy, 578 Radiolabeled, 548, 578, 601 Radiological, 152, 160, 167, 176, 185, 189, 216, 244, 254, 264, 265, 266, 387, 414, 433, 578 Radiology, 162, 229, 563, 578 Radiotherapy, 125, 508, 548, 578, 601 Radium, 578 Radon, 302, 578 Randomized clinical trial, 200, 578 Randomized Controlled Trials, 248, 304, 579 Rarefaction, 395, 579 Reactivation, 196, 579
620 Rheumatoid Arthritis
Reactive Oxygen Species, 231, 579 Reagent, 436, 519, 579 Reality Testing, 576, 579 Receptors, Serotonin, 579, 585 Recombination, 47, 107, 535, 579 Reconstitution, 61, 67, 87, 346, 579 Rectum, 503, 508, 516, 523, 532, 534, 545, 550, 575, 579, 591 Red blood cells, 529, 540, 565, 579, 583 Reductase, 92, 171, 204, 557, 579 Refer, 1, 509, 516, 524, 532, 533, 540, 552, 553, 560, 562, 576, 578, 579, 585, 595 Reflective, 349, 579 Refraction, 579, 588 Refractory, 9, 59, 153, 274, 352, 579 Regeneration, 71, 531, 579, 580 Regimen, 4, 48, 97, 106, 295, 335, 340, 341, 347, 365, 407, 514, 525, 580, 581 Regression Analysis, 90, 292, 580 Regurgitation, 539, 580 Relapse, 250, 256, 278, 442, 580 Relative risk, 66, 349, 580 Reliability, 33, 236, 580 Remission, 49, 97, 114, 167, 189, 218, 228, 249, 251, 305, 388, 414, 555, 580 Renal failure, 148, 157, 580 Renal pelvis, 375, 580 Renal tubular, 305, 520, 580 Renal tubular acidosis, 305, 580 Reproduction Techniques, 573, 580 Research Design, 13, 15, 580 Resection, 248, 580 Resolving, 302, 580 Resorption, 23, 113, 156, 435, 565, 580 Respiration, 156, 503, 558, 565, 580 Respiratory Burst, 280, 581 Response rate, 198, 581 Restoration, 13, 71, 382, 569, 579, 581, 601 Retina, 355, 514, 517, 550, 564, 581, 585, 598, 600 Retinal, 229, 281, 532, 564, 581, 582, 600 Retinoid, 31, 581 Retinol, 581, 582 Retreatment, 245, 581 Retrospective, 105, 251, 282, 305, 581 Retroviral vector, 53, 535, 581 Retrovirus, 61, 373, 581 Reverse Transcriptase Polymerase Chain Reaction, 72, 581 Rheology, 68, 581 Rheumatoid Nodule, 254, 385, 582 Rhinitis, 405, 582
Rhodopsin, 564, 581, 582 Ribonuclease, 122, 582 Ribose, 144, 496, 520, 571, 582 Ribosomal Proteins, 151, 582 Rigidity, 570, 582 Rituximab, 218, 294, 442, 582 Ruminants, 537, 582 Rutin, 303, 582 S Saimiri, 547, 582 Salicylate, 582 Salicylic, 582 Salicylic Acids, 582 Saliva, 68, 212, 437, 438, 582 Salivary, 27, 437, 438, 479, 480, 523, 530, 582, 586, 590, 601 Salivary glands, 437, 438, 479, 480, 523, 530, 582, 586 Salvage Therapy, 210, 583 Saponins, 583, 589 Sarcoidosis, 438, 583 Sarcoma, 212, 531, 583 Scalpel, 50, 583 Scans, 57, 155, 339, 341, 345, 583 Scatter, 568, 583 Schizoid, 583, 601 Schizophrenia, 106, 583, 601 Schizotypal Personality Disorder, 583, 601 Sclera, 514, 517, 528, 583, 598 Scleritis, 54, 260, 583 Scleroderma, 313, 344, 361, 426, 438, 479, 480, 531, 583 Scleroproteins, 549, 584 Sclerosis, 43, 160, 280, 394, 407, 411, 426, 516, 559, 584 Screening, 19, 21, 32, 34, 256, 282, 337, 343, 345, 355, 374, 418, 514, 584 Sebaceous, 522, 584 Sebaceous gland, 522, 584 Secondary tumor, 557, 584 Secretory, 71, 89, 412, 584 Sediment, 374, 584 Sedimentation, 171, 186, 269, 355, 381, 383, 391, 396, 397, 492, 512, 571, 584, 597 Segmental, 58, 584 Segmentation, 584 Segregation, 69, 506, 535, 579, 584 Selection Bias, 38, 584 Selenium, 278, 287, 307, 403, 584 Self Care, 496, 584 Self Tolerance, 411, 584 Self-Help Groups, 477, 584
Index 621
Sella, 570, 584 Semisynthetic, 514, 558, 585 Senile, 565, 585 Senility, 462, 585 Sensitization, 389, 585 Sepsis, 214, 585 Septic, 81, 94, 504, 585 Septicemia, 256, 585 Sequela, 23, 585 Sequencing, 10, 61, 87, 93, 571, 585 Sequester, 71, 585 Serine, 108, 520, 527, 576, 585, 597 Serine Endopeptidases, 527, 585 Serologic, 54, 257, 543, 585 Serology, 388, 414, 479, 585 Serotonin, 154, 562, 579, 585, 597 Serous, 527, 571, 585 Serrata, 317, 318, 514, 585 Serrated, 585 Serum Sickness, 543, 585 Sex Characteristics, 496, 500, 585, 586, 593 Sex Distribution, 585, 586 Sex Factors, 62, 586 Sharpness, 586, 600 Shedding, 24, 207, 586 Shock, 67, 94, 96, 221, 371, 406, 500, 586, 596 Sicca, 144, 586 Signal Transduction, 16, 24, 31, 69, 82, 101, 111, 116, 120, 409, 586 Signs and Symptoms, 46, 94, 98, 278, 292, 347, 350, 402, 474, 571, 580, 586 Sirolimus, 544, 586 Skeletal, 100, 205, 404, 500, 514, 559, 560, 586, 587, 597 Skeleton, 90, 388, 414, 496, 531, 549, 574, 586, 594 Skull, 519, 564, 586, 592 Sleep apnea, 115, 586 Sleep Deprivation, 115, 587 Small intestine, 193, 514, 525, 541, 548, 587, 597 Smooth muscle, 500, 504, 509, 518, 541, 559, 562, 587, 590 Sneezing, 586, 587 Soaps, 532, 587 Social Environment, 577, 587 Social Perception, 230, 587 Social Security, 579, 587 Social Support, 11, 47, 104, 161, 247, 587, 589
Sodium, 121, 287, 403, 406, 523, 528, 537, 558, 560, 587, 591, 595 Soft tissue, 268, 391, 508, 531, 586, 587 Solid tumor, 126, 501, 527, 587 Soma, 359, 587 Somatic, 50, 64, 109, 133, 141, 201, 496, 541, 551, 555, 558, 568, 573, 587 Sound wave, 523, 579, 587 Soybean Oil, 572, 587 Spasm, 7, 478, 587 Spatial disorientation, 524, 587 Specialist, 164, 272, 481, 523, 587 Spectrometer, 110, 588 Spectrum, 35, 95, 219, 391, 404, 515, 578, 588 Sperm, 59, 500, 514, 588, 597 Spinal cord, 508, 509, 512, 513, 526, 555, 556, 561, 568, 588, 591 Spinous, 528, 549, 588 Spirochete, 42, 588 Spleen, 5, 13, 78, 109, 397, 468, 490, 500, 553, 583, 588 Splenomegaly, 395, 588 Spondylarthritis, 245, 588 Spondylitis, 15, 119, 166, 244, 366, 412, 436, 448, 463, 468, 476, 477, 588 Spontaneous Abortion, 573, 588 Stabilization, 5, 7, 235, 385, 588 Staging, 583, 588 Standard therapy, 340, 588 Standardize, 68, 120, 588 Staphylococcus, 558, 588 Stasis, 302, 588 Statistically significant, 106, 588 Stem cell transplantation, 169, 295, 346, 539, 589 Stem Cells, 87, 102, 112, 468, 538, 539, 589 Sterile, 8, 145, 260, 504, 589 Sterility, 520, 589 Steroid, 12, 31, 90, 117, 157, 181, 260, 400, 411, 446, 447, 519, 573, 583, 589 Steroid therapy, 12, 589 Stillbirth, 573, 589 Stimulant, 509, 541, 549, 589, 598 Stimulus, 69, 524, 525, 529, 547, 550, 577, 589, 593 Stomach, 313, 379, 495, 523, 529, 533, 534, 541, 550, 561, 567, 568, 582, 587, 588, 589 Strand, 147, 164, 200, 213, 214, 222, 236, 248, 251, 272, 295, 300, 571, 589 Streptococcal, 71, 435, 551, 589 Streptococcus, 531, 589
622 Rheumatoid Arthritis
Stress management, 4, 589 Stroke, 109, 356, 460, 510, 589 Stromal, 23, 49, 141, 155, 260, 589 Stromal Cells, 141, 589 Stromelysin 1, 242, 589 Structure-Activity Relationship, 17, 590 Subacute, 7, 250, 545, 590 Subarachnoid, 539, 569, 590 Subcapsular, 447, 590 Subclinical, 78, 545, 590 Subcutaneous, 43, 67, 117, 261, 334, 337, 340, 352, 386, 391, 395, 491, 525, 566, 582, 590, 595 Subiculum, 541, 590 Sublingual, 386, 590 Submaxillary, 528, 590 Subspecies, 588, 590 Substance P, 361, 556, 579, 584, 590 Substrate, 127, 130, 255, 366, 511, 520, 527, 548, 590 Substrate Specificity, 130, 590 Suction, 532, 590 Sulfur, 530, 557, 590 Sulindac, 323, 362, 363, 368, 404, 590 Superantigens, 60, 76, 84, 590 Superoxide, 222, 581, 590 Superoxide Dismutase, 222, 590 Supplementation, 76, 92, 297, 299, 300, 301, 307, 591 Support group, 478, 479, 493, 591 Suppositories, 534, 591 Suppression, 14, 36, 37, 40, 63, 77, 99, 106, 114, 124, 243, 303, 344, 384, 398, 402, 435, 519, 591 Suppressive, 13, 261, 407, 591 Suprofen, 407, 591 Survival Analysis, 119, 591 Survival Rate, 341, 565, 591 Sweat, 522, 591 Sweat Glands, 522, 591 Sympathectomy, 402, 591 Sympathetic Nervous System, 401, 505, 591 Symptomatic, 231, 246, 359, 400, 401, 407, 591 Symptomatology, 134, 260, 279, 293, 591 Synapse, 130, 497, 562, 591, 596 Synaptic, 562, 586, 591 Syncope, 591, 599 Synergistic, 15, 97, 118, 262, 365, 390, 567, 574, 591 Synovial Cyst, 261, 592
Synovial Membrane, 49, 107, 137, 159, 160, 351, 365, 368, 372, 385, 392, 409, 415, 418, 421, 444, 549, 592 Systemic disease, 123, 381, 396, 397, 438, 585, 592 Systemic therapy, 513, 592 Systolic, 21, 162, 542, 592 Systolic blood pressure, 21, 162, 592 T Tachycardia, 118, 391, 592 Tachyphylaxis, 405, 592 Tacrolimus, 349, 350, 544, 592 Talus, 592, 594 Taurine, 204, 257, 592 Telophase, 557, 592 Temporal, 20, 46, 74, 90, 100, 499, 539, 541, 572, 592, 599 Temporal Lobe, 499, 592, 599 Tendon, 7, 100, 173, 243, 256, 270, 409, 509, 592, 593 Tenosynovitis, 305, 423, 593 Teratogenic, 419, 498, 593 Teratogenicity, 419, 593 Terminator, 515, 593 Testicle, 340, 537, 593 Testis, 593 Testosterone, 15, 152, 579, 593 Tetani, 593 Tetanic, 593 Tetanus, 359, 593 Tetracycline, 8, 383, 524, 558, 593 Thalamus, 523, 551, 573, 593, 599 Therapeutics, 19, 115, 144, 280, 311, 372, 425, 430, 453, 593 Thermal, 7, 508, 524, 562, 571, 593 Thigh, 94, 577, 593 Thioguanine, 397, 593 Thorax, 495, 553, 593 Threonine, 417, 576, 585, 593 Threshold, 94, 103, 542, 593 Thrombin, 530, 531, 570, 575, 593, 594 Thrombocytopenia, 118, 252, 359, 593 Thromboembolism, 161, 593 Thrombolytic, 570, 594 Thrombomodulin, 575, 594 Thrombopoietin, 154, 594 Thrombosis, 204, 506, 546, 575, 589, 594 Thromboxanes, 404, 503, 520, 525, 594 Thrombus, 519, 545, 570, 594 Thrush, 510, 594 Thymus, 543, 553, 594 Thyroid, 197, 299, 432, 537, 542, 594, 597
Index 623
Thyroid Gland, 537, 542, 594 Thyroiditis, 84, 594 Tibia, 146, 279, 531, 594 Time Management, 589, 594 Tin, 396, 397, 491, 511, 594 Tinea Pedis, 522, 594 Tinidazole, 398, 594 Tissue Distribution, 47, 73, 509, 594 Tissue Extracts, 10, 594 Tolerance, 7, 21, 53, 90, 97, 99, 131, 132, 279, 349, 352, 354, 389, 405, 496, 536, 584, 595 Tolmetin, 362, 363, 368, 404, 595 Tome, 305, 318, 595 Tomography, 5, 89, 353, 517, 583, 595 Tone, 402, 564, 595 Tonicity, 549, 595 Tonsil, 259, 595 Tonsillitis, 259, 595 Tonus, 595 Tooth Preparation, 496, 595 Tophus, 187, 595 Topical, 23, 292, 321, 452, 542, 587, 595 Torsion, 545, 595 Tourniquet, 161, 595 Toxic, iv, 126, 344, 359, 364, 369, 390, 401, 403, 405, 447, 474, 498, 521, 526, 527, 538, 543, 544, 584, 592, 595 Toxicology, 152, 462, 595 Toxin, 527, 593, 595 Trace element, 508, 594, 595 Trachea, 509, 568, 594, 595 Traction, 7, 596 Tranexamic Acid, 233, 596 Transcriptase, 137, 581, 596 Transcription Factors, 30, 31, 40, 69, 78, 91, 94, 100, 102, 596 Transcutaneous, 310, 463, 596 Transdermal, 15, 596 Transduction, 12, 53, 59, 70, 87, 111, 120, 586, 596 Transfection, 53, 100, 110, 507, 535, 596 Transfer Factor, 543, 596 Transforming Growth Factor beta, 230, 596 Transfusion, 154, 596 Transgenes, 17, 60, 596 Translation, 499, 535, 561, 596 Translational, 87, 596 Transmitter, 495, 555, 562, 596 Transplantation, 60, 87, 391, 526, 543, 554, 596
Trauma, 161, 186, 253, 438, 596 Trees, 38, 55, 596 Triamcinolone Acetonide, 8, 596 Tropomyosin, 597 Troponin, 185, 597 Trypsin, 433, 527, 597 Trypsin Inhibitors, 433, 597 Tryptophan, 63, 516, 585, 597 Tubocurarine, 534, 597 Tubulin, 557, 597 Tumor marker, 507, 597 Tumor suppressor gene, 141, 597 Tumour, 135, 150, 174, 191, 198, 206, 209, 216, 253, 256, 264, 266, 269, 271, 563, 597 Tyrosine, 69, 116, 234, 268, 306, 441, 597 U Ubiquitin, 110, 597 Ulcer, 558, 567, 597, 599 Ulceration, 281, 302, 550, 597 Ulcerative colitis, 214, 252, 434, 545, 597 Ulna, 248, 597 Ultrasonography, 143, 162, 177, 203, 205, 209, 270, 597 Unconscious, 521, 543, 598 Unsaturated Fats, 532, 598 Urea, 358, 505, 564, 591, 598 Uremia, 580, 598 Ureter, 580, 598 Urethra, 575, 598 Uric, 537, 542, 577, 598 Urinary, 76, 118, 142, 170, 375, 378, 478, 505, 510, 514, 520, 598 Urinary tract, 118, 375, 505, 598 Urinary tract infection, 118, 375, 505, 598 Urine, 201, 247, 336, 340, 341, 343, 344, 374, 505, 507, 519, 524, 528, 575, 577, 580, 598 Urticaria, 359, 500, 585, 598 Uterus, 495, 513, 519, 526, 532, 533, 556, 566, 573, 598 Uvea, 598 Uveitis, 245, 262, 267, 268, 313, 354, 355, 598 V Vaccination, 8, 43, 48, 61, 80, 185, 272, 389, 598 Vaccine, 48, 76, 391, 405, 496, 575, 598 Vagina, 510, 513, 556, 598 Vaginal, 553, 598 Vaginitis, 510, 598 Vagotomy, 115, 598 Valine, 567, 598
624 Rheumatoid Arthritis
Varicose, 550, 599 Varicose Ulcer, 550, 599 Vascular endothelial growth factor, 124, 149, 173, 599 Vasculitis, 54, 273, 346, 369, 384, 395, 398, 404, 434, 489, 571, 599 Vasodilation, 543, 599 Vasodilator, 508, 541, 599 VE, 156, 599 Vector, 12, 36, 50, 51, 60, 87, 376, 566, 596, 599 Vein, 340, 345, 353, 548, 563, 566, 599 Venom, 309, 418, 419, 599 Venous, 506, 507, 509, 550, 562, 570, 575, 599 Venous blood, 507, 509, 570, 599 Ventricle, 499, 541, 543, 577, 592, 593, 599 Venules, 508, 510, 527, 599 Vertebrae, 547, 588, 599 Vertebral, 246, 248, 274, 570, 599 Vertebrobasilar Insufficiency, 151, 599 Vertigo, 599 Vesicular, 522, 540, 599 Veterinary Medicine, 403, 461, 599 Villous, 511, 599 Vinblastine, 406, 597, 599 Vinca Alkaloids, 406, 599, 600 Vincristine, 406, 597, 600 Viral, 28, 50, 51, 61, 120, 121, 373, 394, 395, 401, 411, 416, 418, 419, 526, 535, 545, 563, 581, 596, 600 Viral vector, 50, 51, 120, 121, 600 Virion, 505, 600 Virulence, 42, 76, 595, 600 Virulent, 76, 600 Viscosity, 68, 581, 600 Visual Acuity, 355, 583, 600
Vitamin K, 351, 600 Vitreous, 355, 550, 581, 600 Vitreous Body, 581, 600 Vitro, 12, 15, 23, 24, 29, 31, 44, 47, 49, 59, 63, 67, 68, 70, 73, 74, 79, 86, 87, 91, 94, 95, 96, 101, 102, 114, 116, 125, 126, 127, 128, 138, 189, 204, 224, 417, 435, 526, 535, 540, 545, 571, 585, 592, 600 Vivo, 11, 12, 17, 22, 24, 26, 29, 30, 31, 36, 37, 39, 44, 47, 50, 51, 59, 63, 70, 73, 75, 77, 78, 84, 85, 86, 87, 94, 100, 101, 108, 110, 114, 118, 123, 126, 127, 129, 189, 205, 224, 264, 330, 387, 410, 417, 435, 535, 540, 545, 590, 592, 594, 600 Voluntary Health Agencies, 112, 600 W Walkers, 462, 600 Weight Gain, 446, 600 Weight-Bearing, 463, 600 White blood cell, 60, 348, 492, 501, 531, 538, 545, 551, 553, 554, 559, 560, 562, 570, 600 Windpipe, 568, 594, 600 Withdrawal, 211, 251, 398, 601 Wound Healing, 70, 419, 511, 531, 546, 555, 601 X Xenograft, 501, 601 Xerostomia, 5, 437, 438, 480, 549, 601 X-ray therapy, 548, 601 Y Yeasts, 510, 533, 569, 601 Yin Deficiency, 308, 601 Yttrium, 126, 173, 601 Z Zymogen, 575, 601
Index 625
626 Rheumatoid Arthritis
Index 627
628 Rheumatoid Arthritis
