Degenerative Joint Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

DEGENERATIVE JOINT DISEASE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NT...

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DEGENERATIVE JOINT DISEASE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

DEGENERATIVE JOINT DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Degenerative Joint Disease: 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: 0-497-00340-6 1. Degenerative Joint Disease-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 degenerative joint disease. 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 DEGENERATIVE JOINT DISEASE ................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Degenerative Joint Disease ........................................................... 4 E-Journals: PubMed Central ....................................................................................................... 17 The National Library of Medicine: PubMed ................................................................................ 17 CHAPTER 2. NUTRITION AND DEGENERATIVE JOINT DISEASE ...................................................... 35 Overview...................................................................................................................................... 35 Finding Nutrition Studies on Degenerative Joint Disease .......................................................... 35 Federal Resources on Nutrition ................................................................................................... 36 Additional Web Resources ........................................................................................................... 37 CHAPTER 3. ALTERNATIVE MEDICINE AND DEGENERATIVE JOINT DISEASE ................................ 39 Overview...................................................................................................................................... 39 National Center for Complementary and Alternative Medicine.................................................. 39 Additional Web Resources ........................................................................................................... 39 General References ....................................................................................................................... 41 CHAPTER 4. DISSERTATIONS ON DEGENERATIVE JOINT DISEASE .................................................. 43 Overview...................................................................................................................................... 43 Dissertations on Degenerative Joint Disease ............................................................................... 43 Keeping Current .......................................................................................................................... 44 CHAPTER 5. PATENTS ON DEGENERATIVE JOINT DISEASE ............................................................ 45 Overview...................................................................................................................................... 45 Patents on Degenerative Joint Disease ........................................................................................ 45 Patent Applications on Degenerative Joint Disease..................................................................... 49 Keeping Current .......................................................................................................................... 52 CHAPTER 6. BOOKS ON DEGENERATIVE JOINT DISEASE ................................................................ 53 Overview...................................................................................................................................... 53 Chapters on Degenerative Joint Disease ...................................................................................... 53 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 57 Overview...................................................................................................................................... 57 NIH Guidelines............................................................................................................................ 57 NIH Databases............................................................................................................................. 59 Other Commercial Databases....................................................................................................... 61 APPENDIX B. PATIENT RESOURCES ................................................................................................. 63 Overview...................................................................................................................................... 63 Patient Guideline Sources............................................................................................................ 63 Finding Associations.................................................................................................................... 70 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 73 Overview...................................................................................................................................... 73 Preparation................................................................................................................................... 73 Finding a Local Medical Library.................................................................................................. 73 Medical Libraries in the U.S. and Canada ................................................................................... 73 ONLINE GLOSSARIES.................................................................................................................. 79 Online Dictionary Directories ..................................................................................................... 79 DEGENERATIVE JOINT DISEASE DICTIONARY................................................................. 81 INDEX .............................................................................................................................................. 115

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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 degenerative joint disease 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 degenerative joint disease, 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 degenerative joint disease, 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 degenerative joint disease. 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 degenerative joint disease, 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 degenerative joint disease. The Editors

1 From

the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON DEGENERATIVE JOINT DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on degenerative joint disease.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and degenerative joint disease, 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 “degenerative joint disease” (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: •

Stickler Syndrome: Report of Four Cases Source: Annals of Dentistry. 52(2): 23-27. Winter 1993. Summary: This article reports four patients with Stickler syndrome, an autosomal dominant connective tissue disorder. The characteristic features of Stickler syndrome include eye manifestations like myopia, vitreo-retinal degeneration, cataracts, and retinal detachment; facial changes of mid-face hypoplasia, broad nasal bridge, Pierre Robin sequence, and epiphyseal dysplasias; and premature degenerative joint disease. Since most of these patients will have cleft palate and facial anomalies, many of them initially consult oral surgeons. A correct diagnosis of the condition is of paramount importance because of the possibility of preventing blindness, and of its genetic implications. The authors report these four cases, and discuss features of other similar

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syndromes to facilitate the early and correct diagnosis of affected individuals. The authors conclude that Stickler syndrome should be considered in any newborn infant with Pierre Robin sequence or cleft palate and small chin; and in all cases of dominantly inherited myopia with or without retinal detachments, dominantly inherited cleft palate, and dominantly inherited mild spondylo-epiphyseal dysplasia with or without joint laxity and slender tubular bones. 4 figures. 2 tables. 10 references. (AA-M).

Federally Funded Research on Degenerative Joint Disease The U.S. Government supports a variety of research studies relating to degenerative joint disease. 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 degenerative joint disease. 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 degenerative joint disease. The following is typical of the type of information found when searching the CRISP database for degenerative joint disease: •

Project Title: AEROBIC OSTEOARTHRITIS

EXERCISE

INTERVENTION

FOR

KNEE

Principal Investigator & Institution: Kaufman, Kenton R.; Professor of Bioengineering; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Arthritis is one of the most common causes of functional limitation and dependency in the United States. Individuals with osteoarthritis restrict joint motion and limit activity in order to decrease their symptoms. Traditional, conservative medical treatment of osteoarthritis has been directed at improving functional status through reducing joint pain and inflammation and maintaining or restoring joint function. Exercise as an adjunct therapy in the clinical management of patients with osteoarthritis of the knee, however, is not uniformly accepted. In contrast, exercise has been shown to be effective for prevention and treatment of cardiovascular and metabolic disorders. Standard guidelines exist for aerobic exercise prescriptions. The focus of this study is to determine if these guidelines can also be applied to individuals with knee osteoarthritis. Patients with knee osteoarthritis will be randomized into a control group, a walking exercise group, and a stationary cycling exercise group. The individuals in the exercise groups will be required to exercise three times per week for one year using emerging public health recommendations for aerobic exercise in the adult and aging population. Patient 2 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).

Studies

5

outcome will be assessed using objective gait analysis measurements, knee radiographs to quantify joint space narrowing, magnetic resonance imaging, a general health status questionnaire (SF-36), a disease/site specific questionnaire (WOMAC), and a visualanalog pain scale. All subjects will be studied at 0 and 52 weeks. The central hypothesis of this work is that aerobic exercise can be successfully implemented as an effective nonsurgical option for treatment of patients with early stages of knee osteoarthritis. In order to evaluate this hypothesis, the following specific aims are proposed: Specific Aim 1: Determine the effect of aerobic exercise on patients with knee osteoarthritis. Hypothesis A: Clinical Outcome measures will be better in patients enrolled in exercise programs that in control patients. Hypothesis B: Quantitative measures of lower extremity function will not decline over time in an effective aerobic exercise program. Specific Aim 2: Determine prognostic factors that effect outcome in patients with knee osteoarthritis. Hypothesis: A effective exercise prescription for adults with degenerative joint disease is dependent on knee compartment involvement, CIA stage, BMI, and type of exercise prescribed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHONDROPROGENITOR CELLS IN MATURE CARTILAGE Principal Investigator & Institution: Lotz, Martin K.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Osteoarthritis (OA) is one of the most common musculoskeletal disorders in older individuals. Profound aging- associated changes in chondrocytes and cartilage extracellular matrix represent a major factor in OA pathogenesis. Although referred to as a degenerative joint disease, OA is an active cartilage remodeling process. Cells in OA cartilage are activated and not only produce matrix degrading enzymes, but also new extracellular matrix. The remodeling process ultimately fails because of an imbalance between matrix synthesis and degradation, because the newly formed cartilage is non-hyaline repair tissue and matrix is often abnormally calcified. Our preliminary studies suggest that adult human articular cartilage contains chondroprogenitor cells. The proposed experiments are based on the following hypotheses: 1) Mesenchymal progenitor cells are present in adult cartilage, and they can be isolated, expanded and induced to differentiate to multiple mature mesenchymal phenotypes. 2) The frequency, localization, activation and response patterns of mesenchymal progenitor cells are altered in aging and osteoarthritis. 3) The genetic basis of mesenchymal cell differentiation from the progenitor to the discrete subsets of mature chondrocytes can be established with DNA microarrays to define markers and regulators of this process. The following specific aims will test these hypotheses: 1) Determine the frequency and localization of progenitor cells in normal human articular cartilage using immunohistochemistry, cell isolation, flow cytometry and functional assessment of pluripotential differentiation. With these studies, we will develop markers for identification of progenitor cells and methods for isolation and expansion. 2) Analyze the presence of progenitor cells in aging and osteoarthritic human cartilage. Determine whether there is an aging- associated reduction in the number of progenitor cells, whether the cells have an impaired responsiveness to growth factors and whether progenitor cells are associated with the clusters of proliferating chondrocytes and areas of calcified cartilage. 3) With the DNA microarrays, define the genetic basis for the chondrocyte subsets in the various zones of normal human articular cartilage. Establish the relationship between bone marrow derived and cartilage derived progenitors and differentiated chondrocytes generated from them. The discovery of

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progenitor cells in adult cartilage opens new perspectives to harness these cells in cartilage repair and raises the possibility that aging- associated changes in their frequency or function determine joint aging and that they contribute to the aberrant cartilage remodeling process in arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPUTATIONAL FRAMEWORK FOR SIMULATING JOINT MECHANICS Principal Investigator & Institution: Fregly, Benjamin J.; Assistant Professor; Mechanical & Aerospace Engineering; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: Mechanical loading and especially dynamic loading, is believed to play a major role in degenerative joint diseases. Furthermore, motion (i.e., kinematics) and loading (i.e., contact stresses) often interact to influence disease progression. Thus, knowledge of in vivo joint motion and loading during functional activities would help address this clinically significant issue. While dynamic imaging advances now permit accurate measurement of in vivo joint kinematics, a non-invasive experimental approach does not exist for measuring in vivo joint loading. Consequently, computer simulations have been used to develop predictions given estimates of the muscle forces acting on the joint. However, current rigid body and deformable modeling approaches are not able to calculate contact stress results during movement in critical joints such as the knee. A logical solution to this problem is to incorporate deformable joint models into a larger rigid body dynamic model, thereby obtaining the advantages of both approaches. However, the computation cost of such a hybrid approach is currently a limiting factor. This project therefore proposes the development of a parallel-processing framework for studying human joint mechanics. The specific aims of the project are as follows: (1) Create a dynamic musculoskeletal model with deformable knee joint contact. Deformable contact in the knee will be studied initially since the knee is the most commonly injured joint. (2) Incorporate this model into a parallel-processing optimization framework. Parallel processing will be used to reduce the computational time for predictive optimizations from weeks to a matters of hours. (3) Evaluate the model's ability to predict experimental movement data. Pre-existing experimental movement data will be used to evaluate the model's ability to predict motion and ultimately joint contact stresses. The resulting functional virtual human model can then be used for basic research and clinical applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DIFFUSE OPTICAL TOMOGRAPHY OF OSTEOARTHRITIS Principal Investigator & Institution: Jiang, Huabei; Professor; Physics and Astronomy; Clemson University 300 Brackett Hall Clemson, Sc 296345702 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 30-APR-2008 Summary: (provided by applicant): Osteoarthritis (OA), or degenerative joint disease, is the most common form of joint diseases. It is a slowly progressing disease, and a major cause of morbidity in the population over 50, affecting more than 40 million Americans. It also imposes considerable expense on the health care system. While there is currently no cure for this disease, recent studies have shown that the progression of articular damage may be modified by medical or surgical intervention if the disease is detected early. These studies coupled with recent developments in gene therapy have generated substantial demand for noninvasive techniques for detecting early changes in

Studies

7

the joints, when intervention is likely to have its greatest effect. X-ray radiography is excellent for imaging hard tissues and has been a routine modality for examining OA, primarily for advanced OA stages. The limitation of x-ray is its incapability for imaging soft tissues in the joints as well as its incapability for obtaining physiological information related to the functioning of OA. Diffuse optical tomography (DOT) is a promising method for detecting changes in cartilage and inflammation process in synovium. It can also provide information about the functioning and progression of OA. However, DOT has limited spatial resolution comparing to x-ray. To overcome this limitation, in this application we propose a combined x-ray/DOT approach so that we can use the x-ray images as structure guidance for DOT reconstruction. We aim to advance 3D DOT imaging of joint tissue co-registered with 3D x-ray tomosynthesis. Our specific aims include (1) investigation of several tomosynthetic reconstruction methods for 3D x-ray imaging, (2) development of algorithms for segmentation of 3D xray images, (3) development of 3D rendering environment, (4) advanced DOT reconstruction methods including automatic adaptive meshing scheme, parallel computing and a higher-order diffusion model, (5) design, construction and testing of a combined digital x-ray/optical imaging system for 3D imaging of joint tissue, (6) evaluation and optimization of this system using tissue phantom experiments, and (7) testing and evaluation of the combined xray/ optical imaging system in human subjects. If successful, the proposed mulfi-modality imaging method will have a major impact on the ability to make an early and appropriate therapeutic intervention, routinely monitor the progression/clinical outcome and assist in evaluating new treatment modalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EARLY DIAGNOSIS OF GROWTH DISORDERS UING MR IMAGING Principal Investigator & Institution: Jaramillo, Diego; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-JUL-1994; Project End 30-JUN-2005 Summary: (provided by applicant): The goal of this research is the detection of epiphyseal ischemia and prediction of its growth sequelae using novel non-invasive magnetic resonance (MR) approaches. In animal models, we propose to determine the earliest changes in ischemia, to differentiate early from late ischemia leading to avascular necrosis; and to predict the deverlopment of growth arrest. In addition to conventional MR measures (proton density and T2 relaxation), we will investigate perfusion-related changes by early gadolinum (Gd) enhanced imaging; and diffusion related changes by line diffusion scanning and diffusion tensor imaging. We will also evaluate disturbances of the cartilaginous matrix including glycosaminoglycan depletion revealed by delayed GD enhanced imaging, and collagen content by magnetization transfer imaging. The major hypotheses are that MR parameters can 1) detect early ischemia, 2) differentiate early from late ischemia leading to sequelae, and 3) predict growth deformity through MR parameters that reflect tissue structure and vascularization of the immature epiphysis. Epiphyseal ischemia is a pathogenic pathway shared by many common pediatric disorders. Ischemia leading to avascular necrosis of the femoral head frequently causes hip deformity and disability in childhood. A hip that grows abnormally also predisposes to degenerative joint disease in adult; more than half of all adults with osteoarthritis of the hip suffered hip diseases as children. Imaging of cartilaginous disorders serves to guide early therapy, prevent or minimize deformity, and detect children predisposed to premature cartilage degeneration in adulthood. The specific aims are to: 1) determine the MR tissue

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characteristics of normal epiphyseal cartilage. Specifically, we wish to test whether the greater cellularity and vascularization of immature epiphyseal cartilage result in different MR tissue characteristics; 2) in early ischemia, determine temporal and spatial differences between diffusion imaging, T2 maps and Gd-enhanced imaging; 3) in prolonged ischemia, determine which MR parameters best predict irreversible damage; and 4) in a model of avascular necrosis, determine which MR parameters predict abnormal growth. 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 029034923 Timing: Fiscal Year 2002; 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

•

Project Title: IN VIVO RABBIT MODEL OF FINGER MUSCOLOSKELETAL DISORDERS Principal Investigator & Institution: King, Karen B.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007

Studies

9

Summary: (provided by applicant): The ongoing rise in costs and morbidity associated with occupational musculoskeletal disorders (MSDs) demands the investigation of known risk factors for injury. Repetition of movement, forceful loading and their combination (repetitive loading) are risk factors for MSDs. These happen to be some of the few modifiable risk factors for MSDs of the hand and other joints. This project proposes to use an in vivo animal model of repetitive finger joint loading to elucidate the relative risks of these factors (repetition and combined force and repetition). Finger joint loading is used to simulate hand intensive tasks found in the workplace to test the following hypothesis: The combination of force and repetition is an occupational risk factor for MSD. This project will quantify the structural and molecular changes in joint tissues due to repetitive loading. And finally, this project will determine the threshold of repetitive loading in a dose-response study. The long term goals of this study are to 1) determine the relative contributions of individual biomechanical characteristics of finger joint loading, namely repetition, force level, and duration of exposure; and 2) demonstrate causality between these biomechanical risk factors, cellular response, tissue damage, and injury. The results of this mechanobiology project will lead to guidelines for effective interventions of MSDs of the hand joints such as osteoarthritis (OA) or degenerative joint disease (DJD). This project directly addresses the National Occupational Research Agenda (NORA) in 1) developing a quantitative dose-response model identifying dose-response relationships, 2) determining whether the injury response of the tissue has more to do with repetition of loading or level of peak load, and 3) identifying the ultrastructural injury and biochemical alterations associated with physical loading. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LASER ASSISTED CARTILAGE REPAIR USING COLLAGEN ADHESIVES Principal Investigator & Institution: Soltz, Barbara A.; Conversion Energy Enterprises 81 Pine Brook Rd Spring Valley, Ny 10977 Timing: Fiscal Year 2002; Project Start 17-APR-2002; Project End 31-OCT-2002 Summary: Articular cartilage damage affects millions of people. This condition is exacerbated by an ageing but increasingly more active population. The two portentous independent variables associated with inferior treatment of articular cartilage lesions are healing response and cartilage regeneration. Laser-assisted welding using a derivatized collagen solder may aid in the prevention of progressive degenerative joint disease and may augment or ultimately replace total joint arthroplasty. We have assembled a multidisciplinary team to investigate the efficacy of laser activated collagen formulations as an adhesive and as an acellular graft that permits and/or promotes cell invasion. Laser operating parameters will be optimized to promote strong solder crosslinks to cartilage. An integrated temperature controller will be used to prevent peripheral tissue damage. A laser handpiece will be modified for use in the animal studies. Custom designed equipment will be used to accurately measure previously unknown values for inherent solder strength, strength of the repair and type of failure mode. Histology will assess the potential to promote cell invasion and synthesis of new extracellular matrix. It is anticipated that the Phase I results will lay the foundation for further animal studies and clinical trials in subsequent Phase II and Phase III projects. PROPOSED COMMERCIAL APPLICATIONS: The development of laser procedures to repair full thickness articular defects will benefit the millions of people who are suffering from osteoarthritis. This technology may provide orthopaedic surgeons with new techniques which can reduce operating time, convalescence and hospital stays.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANICS OF THE MCL IN NORMAL AND ACL DEFICIENT KNEES Principal Investigator & Institution: Weiss, Jeffrey A.; Bioengineering; University of Utah Salt Lake City, Ut 84102

Associate

Professor;

Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: Knee ligament injury can lead to ligamentous laxity, joint instability and degenerative joint disease. Methodologies that improve the diagnosis, treatment and prevention of ligament injuries are crucial to prevent this progression. The medial collateral ligament (MCL) is one of the most commonly injured knee ligaments, provides primary stabilization against valgus rotation, and is a secondary restraint to anterior tibial translation and external tibial rotation. The structure experiences extreme variations in strain as a function of knee flexion angle. The broad aims of this project are to develop and validate a constitutive model for the MCL, a finite element model of the superficial MCL, and to determine the stress/strain distribution within the MCL under varus-valgus (V-V) torques and anterior-posterior (A-P) tibial force in intact, ACLdeficient, and ACL-deficient+meniscus compromised knees. Following acquisition of volumetric CT data for individual knees, experimental kinematic testing will be performed under V-V and A-P loading conditions as a function of knee flexion angle. Knee kinematics and MCL surface strains will be continuously monitored during all kinematic testing. The MCL will then be isolated from the joint to measure regional in situ strain at 0 degrees knee flexion. Material testing of the MCL will be performed to determine coefficients for a three-dimensional constitutive model. Using the volumetric CT data, detailed geometric and finite element (FE) models of the MCL, distal femur and proximal tibia will be constructed. Appropriate boundary conditions, including representation of contact between the MCL and bones, will be applied to the model, using the experimentally measured joint kinematics to drive the motion of the model. The experimentally measured in situ strains will be applied to the FE model using numerical algorithms developed by the PI. Predictions of MCL stress/strain under V-V and A-P loading will be obtained from FE simulations. The regional MCL strain predictions will be statistically compared with experimental measurements to validate the model. The results for the normal and ACL-deficient knee will be compared to determine the effect of ACL deficiency on MCL stresses under V-V and A-P loading. Information obtained from this study will yield a detailed understanding of the function of the superficial MCL and its propensity for injury in the ACL-deficient and meniscuscompromised knee. The methods developed in conjunction with this research will facilitate future modeling of other ligamentous structures, and the eventual modeling of entire joints. This work will form the basis for the PI's long term research program aimed at the computational modeling of ligaments and joints. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS & PERFORMANCE OF TRACEABLE UHMWPE IMPLANTS Principal Investigator & Institution: Kurtz, Steven M.; School of Biomedical Engineering, Science & Health Systems; Drexel University 3201 Arch Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 07-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Degradation of ultra high molecular weight polyethylene (hereafter, polyethylene) joint replacement components after gamma

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irradiation in air continues to be recognized as a significant clinical problem limiting the longevity of total joint arthroplasties, which represent the standard of care for patients with advanced degenerative joint disease. Oxidative degradation of polyethylene has been associated with accelerated wear, brittle fracture, and delamination of total joint replacement components. Although it is now recognized that the degradation of polyethylene plays an important role in the damage mechanisms of orthopaedic components, it is still unclear the extent to which the mechanical degradation of polyethylene relates to the overall clinical performance of total hip arthroplasty, due in part to the logistical difficulty in tracing the sterilization and shelf aging history of the components, and also due to the experimental difficulty in directly measuring the mechanical behavior of retrieved implants. The range of mechanical behavior associated with traceable, clinically retrieved orthopedic components is critically needed to guide the development of improved polyethylenes, such as the highly crosslinked polyethylenes which have recently been introduced into clinical practice for total hip arthroplasty. The purpose of this proposed research is to examine the influence of mechanical degradation after implantation on the clinical performance of metal-backed acetabular components for total hip arthroplasty. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ARTHROPATHY

BASIS

OF

AN

X-LINKED

INHERITED

Principal Investigator & Institution: Tiller, George E.; Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAR-2005 Summary: Osteoarthritis is a chronic debilitating disease which affects up to 1/3 of the adult population. Growing evidence suggests that genetic factors influence its development, and a better understanding of inherited chondrodysplasias will undoubtedly shed light on the processes common to all degenerative joint disease. Spondyloepiphyseal dysplasia tarda (SEDT) is a chondrodysplasia which is characterized by disproportionate short stature, X-linked inheritance, and degenerative osteoarthritis. The goals of this project are 1) to localize and isolate the gene for SEDT, 2) to identify the molecular alterations responsible for this disease, and 3) to gain insight into the biological function of the gene product. We have studied three SEDT families, including one large pedigree which includes 16 living affected males and at least 20 carrier females. DNA linkage analysis indicates that the SEDT phenotype in these families cosegregates with polymorphic markers on chromosome Xp22, a region previously defined as harboring the SEDT disease gene. To reduce the size of the candidate area, we will expand the sample size within our families, ascertain additional families, and verify locus order by physical methods. We will identify candidate genes which both map to the region and are transcribed in cartilage using expressed sequence tagged sites (ESTs) and cDNA selection techniques. Candidate genes will be prioritized for mutation analysis based on their homology to known genes. Prime candidates will be analyzed for mutations by SSCP and direct DNA sequence analysis of genomic DNA and/or cDNA from affected individuals. This research will directly benefit families with SEDT by enhancing genetic counseling and facilitating early definitive diagnosis for individuals at risk, therefore improving their clinical care. The expression pattern and function of the SEDT gene may provide clues for designing therapeutic modalities for affected individuals. Moreover, we anticipate that the molecular delineation of SEDT will have a significant impact on our understanding of basic mechanisms responsible for

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Degenerative Joint Disease

maintaining cartilage integrity, as well as those contributing to cartilage degeneration in osteoarthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEPOSITION

MOLECULAR

BASIS

OF

CALCIUM

PYROPHOSPHATE

Principal Investigator & Institution: Masuda, Ikuko; Medicine; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 04-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted from the Applicant's Abstract): CPPD crystal deposition in human articular cartilage is a common age-related event, and clinically and epidemiologically associated with degenerative joint disease, another age-related event. CPPD causes arthritis and subsequent cartilage degradation. However, the molecular mechanisms involved in CPPD formation in articular tissues remain undetermined. The goal of this grant proposal is to define the molecular basis of calcium pyrophosphate dehydrate (CPPD) crystal deposition disease. Elevated nucleotide pyrophosphohydrolase (NTPPHase) activity has been observed in CPPD-containing joint fluids and in detergent extracts of CPPD crystal-encrusted degenerated cartilage. NTPPHase catalyzes the joint fluids of PPi from ATP and other nucleotides. Several studies are consistent with the hypothesis that the bulk of PPi production occurs via the hydrolysis of extracellular ATP by ectoNTPPHase. NTPPHase exists in several molecular forms, including a 127kD sedimentable vesicle-associated NTPPHase, and two soluble forms of molecular masses of 100 and 61kD. The 127kD protein appears to represent the mature form of NTPPHase, while the 100 and 61kD forms represent soluble proteolytic fragments of the 127kD NTPPHase. The applicants have successfully cloned a partial cDNA encoding the 61kD NTPPHase fragment of the porcine 127kD NTPPHase from a porcine chondrocyte cDNA library, and also cloned its human homologue from a human chondrocyte cDNA library. Overall, their research has focused on defining the molecular properties of these NTPPHases. The Specific Aims of the current proposal are to: 1) clone the human homologue of the 127kD NTPPHase from a human chondrocyte cDNA library; 2) characterize the enzymatic activity and immunological properties of human 127kD NTPPHase; 3) molecularly characterize the gene that encodes the human NTPPHase; and 4) correlate the expression of the human NTPPHase during aging and disease. It is suggested (by the applicant) that these investigations will provide the framework for the investigators' long-term goal, which is to identify populations at risk, and to design therapeutic approaches, at either the level of transcription or inhibitors of the enzymatic activity of NTPPHase. It is hoped that these studies will lead to therapies to reduce ePPi accumulation and reduce subsequent cartilage degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL OA-MARKERS BY INTEGRATING BASIC BIOLOGY AND CLINIC Principal Investigator & Institution: Heinegard, D K.; University of Lund Box 1703 Lund, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Provided by Applicant): Joint disease like osteoarthritis affects a very large proportion of the population, in the order of 10%, with loss of motion, pain and dysfunction and impaired quality of daily activities. The cost to society rank among the highest for any disease group. Therapy existing today is very limited and largely rely on

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joint replacement. A prerequisite for development of novel therapy is to delineate mechanisms in the progressive joint destruction as well as novel diagnostic procedures that can identify patients with active disease and evaluate therapy that modifies disease progression. This study is to develop new diagnostic procedures that provide insights in mechanisms in osteoarthritis development and thereby facilitate new advances in therapy as well as provide means for identifying patients at risk and for monitoring therapeutic effects. The specific aims are: 1 ) To define processes in the articular cartilage and bone during development of osteoarthritis by monitoring for release of cartilage and bone constituents; 2) To identify new molecules that show a unique distribution to articular cartilage, meniscus and bone in the joint and have potential as molecular markers of processes affecting these structures; 3) To define specific proteolytic cleavage by the identification of neoepitopes formed by specific proteinases active in cartilage destruction. Specific antibodies developed will be used for assays of processes in the tissue leading to proteolytic release of specific fragments; 4) To search for the identity of enzymes accomplishing specific proteolysis of target molecules; 5) To identify disease mechanisms by focusing on bioactive markers that contain active domains that recognize specific ligands on cells of bone, cartilage and synovium and/or can bind to other factors present in the synovial fluid. Assays will be developed for active fragments and their role in the process in the joint will be investigated; 6) To develop quantitative immunoassays for identified proteins that are altered in articular cartilage of degenerative joint disease; 7) To evaluate newly developed assays by analyses of well defined human patient cohorts as well as animal models with or without specific intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL X-RAY TECHNOLOGY FOR DEGENERATIVE JOINT DISEASE Principal Investigator & Institution: Kuettner, Klaus E.; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: We propose a program to integrate biomedical (Rush Medical College) with bioengineering (Illinois Institute of Technology and Massachusetts Institute of Technology) approaches to test and refine a novel X-ray technology for the diagnosis of joint pathology, particularly osteoarthritis. This technology may aid in the development of disease modifying agents and treatment strategies for the prevention and treatment of joint diseases. This project utilizes a novel synchrotron x-ray technique called diffraction enhanced imaging (DEI) which derives dramatic gains in contrast over conventional radiographs by exploiting x-ray refraction and scatter rejection (extinction) in addition to the usual absorption of conventional radiography. This technique, originally developed for mammary carcinoma imaging analyzes soft tissue as high contrast images with very high (greater than 0.05mm) spatial resolution. Although the synchrotron is currently used for DE imaging, the technique is not, in principle, tied to it. We have already shown that DEI is capable of imaging normal and degenerated articular cartilage of synovial joints showing features unique to this type of imaging using exposure times comparable to those of ordinary radiography. Beginning in the first year, we will interpret the cartilage and bone data obtained through our DEI methodologies by using the biological profiles of the matrix components as garnered through morphologic, biochemical and biophysical analysis. Some of the features observed in the DE images are not immediately explainable in molecular, chemical or structural terms. By using a unique integrated experimental approach, correlating biochemical and

14

Degenerative Joint Disease

morphological tissue profiles with DE images, we hope to refine the overall DEI system for the detection of joint disease and, potentially, for other pathologies. We will image human and animal synovial joints and begin the refinement of the imaging technique for the optimal identification of early cartilage lesions. Animal models of cartilage degeneration will be used particularly for DE imaging of cartilage prior to visible signs of degeneration. Beginning in year two, we will image human cartilage that has been biomechanically damaged under controlled conditions for observation through DE imaging. We will also begin developing new DEI methodologies to produce images conveying more comprehensive information about the properties of the cartilage tissue, first for planar and then for 3D computed tomography. Throughout years one through five of the proposed project, there will be an iterative process of comparing biological analytical data with imaging data for the refinement of the DEI technique for joint tissues. Our long-term goal is to identify and localize initial phases of cartilage degeneration and follow their progression with the ultimate aim of monitoring disease progression and therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SHEAR STRESS AND CHONDROCYTE GENE EXPRESSION Principal Investigator & Institution: Smith, Robert L.; Professor-Research; Functional Restoration; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2004 Summary: While the precise etiology of the degenerative joint disease, osteoarthritis, is unknown, clinical manifestations of pain and disability are most often associated with inappropriate mechanical loading. As evident at surgery, focal erosion of articular cartilage culminates in loss of joint function and remains the final common pathway in all cases of osteoarthritis irrespective of cause. The goal of this study is to determine the cellular mechanisms by which mechanical loading influences cartilage matrix synthesis and degradation. In the joint, cartilage cells, chondrocytes, are subject to a complex array of stresses and strains. Our work shows that normal chondrocytes in culture react metabolically to univariate mechanical stimulation applied either as intermittent hydrostatic pressure or as fluid- induced shear stress. The hypothesis to be tested here is that distinct intracellular signaling pathways underlie the articular cartilage response to the two forms of mechanical stimulation. Fundamental knowledge exists regarding the effects of the proinflammatory cytokine, interleukin-1, on inhibition of cartilage extracellular matrix macromolecule synthesis and induction of cartilage degrading enzyme synthesis by chondrocytes. However, the effects of mechanical loading on the expression of articular chondrocyte degradative enzymes in the presence of IL-1 remain unclear. The specific aims will quantify effects of shear stress (SS) and intermittent hydrostatic pressure (IHP) on human osteoarthritic articular chondrocytes in vitro to: (1) Test the hypothesis that IHP and SS differentially modulate extracellular matrix macromolecule expression in OA versus normal chondrocytes; (2) Test the hypothesis that IHP and SS modulate IL-1beta induced inhibition of proteoglycan and type II collagen synthesis in OA and normal chondrocytes; (3) Test the hypothesis that IHP and SS alter endogenous MMPs and aggrecanase expression in OA and normal chondrocytes; (4) Test the hypothesis that IHP and SS alter IL-1beta induced expression of MMPs and aggrecanse in OA and normal chondrocytes. The expected result is that SS and IHP will show dissimilar capacities to overcome the IL-1 induced shift of chondrocyte metabolism from cartilage maintenance to matrix destruction. The results of this study will be of importance to the fields of orthopaedics, rheumatology and rehabilitation medicine. The techniques will involve analysis of proteoglycan and

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collagen synthesis by incorporation of radiolabeled precursors. mRNA signal levels will be quantified by Northern blotting and RT-PCR analysis. Cytokines will be quantified by bioassays and commercially available ELISA. MMPs will be identified by zymography and Western blotting and quantified by Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARTILAGE

STABILIZATION

OF

MATRIX

STRUCTURE

IN

MATURE

Principal Investigator & Institution: Chen, Qian; Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 29-FEB-2004 Summary: Degenerative joint disease or osteoarthritis (OA) is one of the most common disabling diseases affecting middle-aged and older people. It is characterized by the breakdown of an unstable matrix network in cartilage. To better understand the pathogenic process of OA, it is necessary to examine how the matrix structure is stabilized in mature cartilage, and what causes destabilization of such a structure. The long term career goal of the candidate is to analyze the molecular mechanisms of stabilizing matrix networks in mature cartilage. The immediate research plan is to determine the role of cartilage matrix protein (CMP), a mature cartilage specific protein that interacts with both collagenous and non-collagenous matrix components to form a filamentous network, in the stabilizing process. As a newly independent investigator, the candidate is applying for an RCA to protect his research time at 95 percent level and to continue his productive record. This proposal for the next five years of research is based on candidate's recently funded FIRST Award from NIH and the Arthritis Investigator Award from Arthritis Foundation. It contains four specific aims: 1) To characterize the interaction sites between CMP and matrix network. The location and properties of the adhesion sites will be determined by examining the interaction of a series of recombinant CMPs with matrix networks in a primary chondrocyte culture. 2) To analyze the nature of the covalent crosslinking of CMP in cartilage matrix. A monoclonal antibody will be used to determine whether CMP is a substrate for tissue transglutaminase. 3) To determine whether the disruption of interaction and crosslinking of CMP will result in a misassembled or unstable matrix network that is subject to degeneration. The dominant negative CMP constructs will be expressed in cartilage by retroviral infection. The effects will be examined by immunohistochemical analysis. 4) To examine whether abnormal CMP gene expression in human OA articular cartilage leads to a defective matrix structure. In situ hybridization and electron microscopy will be used to analyze abnormal synthesis and assembly of CMP in OA cartilage. These data will contribute not only to our basic understanding of cartilage matrix assembly, but also to the development of methods for prevention and treatment of cartilage degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TISSUE ENGINEERING OF THE TEMPOROMANDICULAR JOINT Principal Investigator & Institution: Ratcliffe, Anthony; President and Ceo; Advanced Tissue Sciences, Inc. 10933 N Torrey Pines Rd La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-OCT-2002 Summary: Temporomandibular disorders are common among the general population, and the effects can be debilitating. Recent studies have emphasized the importance of osteoarthritis (degenerative joint disease) and inflammation in the pathogenesis of

16

Degenerative Joint Disease

temporomandibular joint (TMJ) disorders. The growth of tissues in vitro for in vivo transplantation and repair (tissue engineering) has recently been demonstrated to have immense potential. Recent studies have demonstrated the ability to grow cartilage and meniscal constructs in vitro, for in vivo transplantation into knee joints. The objective of this proposal is to develop cartilage and disc tissue representative of TMJ tissues by tissue engineering. It is anticipated that the in vitro growth of the tissue engineered TMJ cartilage and disc constructs will be enhanced with the application of mechanical load and growth factors. Our governing hypothesis is that tissue engineered constructs similar to TMJ tissues can be generated using scaffolds with TMJ cells, and cultured under defined mechanical loads with selected growth factors. Specific Aim 1 is to (a) determine the capacity of cells from the articular cartilage and the disc of the TMJ to proliferate and maintain a phenotype that will allow construct formation in vitro; and (b determine the scaffold(s) that will support construct growth and generate a tissue similar to that of normal TMJ cartilage and disc. Specific Aim 2 is to determine the effect of (a) static and cyclic compressive loads, (b) fluid induced shear stress, and (c) growth factors (IGF1, TGFb and FGF) on the gene expression and synthesis of aggrecan, biglycan, decorin, caollgen I and II, in the bovine TMJ articular cartilage, and the posterior band and intermediate zone of the disc. Based on these results, we will develop a bioreactor system that will support tissue growth with imposition of the mechanical loads and stresses as identified in (a), (b) and (c). Specific Aim 3 is to determine the effect of specifically selected mechanically loading regimes, and potentially growth factors (as determined in Specific Aim 2), on the ability of cell-seeded scaffolds (as selected in Specific Aim 1) to form cartilage and disc tissue in vitro. The objective will be to use these variables to modulate tissue growth toward the properties and composition of normal TMJ tissues. The completion of these studies will provide the method for tissue engineering TMJ tissues appropriate for transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSDUCTION OF MECHANICAL SIGNALS IN CARTILAGE Principal Investigator & Institution: Towle, Christine A.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 16-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Osteoarthritis (OA) is a common degenerative joint disease that is the leading cause of chronic disability in the United States. OA primarily afflicts those over 50 years of age, but it is distinct from normal aging. The hallmark of the disease is the loss of articular cartilage, a tissue that is essential for normal joint function. The causes of osteoarthritis have not been fully determined, but risk factors include abnormal mechanical loading related to joint injury, joint instability, joint malalignment, and obesity. As such, there is immense interest in understanding the effects of mechanical stimuli on articular cartilage. The hypothesis underlying this proposal is that cartilage deformation on weight-bearing is an important stimulant of progressive degenerative change to the articular cartilage. Preliminary data demonstrate that the inhibition of proteoglycan synthesis that is caused by static compression in calf articular cartilage is ameliorated by IL-1 receptor antagonist and by inhibition of caspase activity, supporting the concept that IL-1 receptors and caspase(s) are critical elements in mechanical signaling and down-stream metabolic effects. The beneficial effect of IL-1 receptor antagonist is an exciting finding that begins to define a signaling pathway activated by mechanical stimulus in cartilage. The broad goal of this proposal is to delineate the linkage between static mechanical compression and the down-regulation of extracellular matrix biosynthesis in cartilage. The goal is approached through four

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Specific Aims. First, studies will evaluate the IL-1 receptor dependency of compression effects on various metabolic parameters in surface and middle-depth bovine cartilage, and in human normal and OA cartilage. Second, studies will identify the specific caspases that are activated in compressed tissue in an attempt to clarify the involvement of caspase(s) in modulating cartilage metabolism. Third, studies will examine the phosphorylation status and levels of selected molecules in the signaling cascade activated by compression, with a focus on IL-1 receptor and caspase dependency. Fourth, studies will examine the role of IL-1 receptor and caspases on the metabolic effects of hyperosmotic and pH-buffered media, which mimic some of the cellular and physiochemical changes that occur with mechanical compression. The research is expected to define the mechanism(s) whereby cartilage deformation activates IL-1 receptor-dependent signaling pathways and modulates cartilage metabolism. 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 “degenerative joint disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for degenerative joint disease in the PubMed Central database: •

Inter-examiner reliability of the diagnosis of cervical pillar hyperplasia (CPH) and the correlation between CPH and spinal degenerative joint disease (DJD). by Stupar M, Mauron D, Peterson CK.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324408

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. 3 Adapted 4

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. 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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Degenerative Joint Disease

To generate your own bibliography of studies dealing with degenerative joint disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “degenerative joint disease” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for degenerative joint disease (hyperlinks lead to article summaries): •

A new anti-inflammatory drug, proquazone, and ibuprofen in the treatment of degenerative joint disease of the knee (gonarthrosis). A double-blind comparative study. Author(s): Puranen J, Ronty H. Source: Scand J Rheumatol Suppl. 1978; (21): 21-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=356237

•

A prospective review of arthroscopic debridement for degenerative joint disease of the knee. Author(s): Aichroth PM, Patel DV, Moyes ST. Source: International Orthopaedics. 1991; 15(4): 351-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1809718

•

Adult degenerative joint disease of the knee. Maximizing function and promoting joint health. Institute for Clinical Systems Integration. Author(s): Lee JA. Source: Postgraduate Medicine. 1999 June; 105(7): 183-6, 189-90, 194 Passim. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10376058

•

Aging in the musculoskeletal system of rhesus monkeys: II. Degenerative joint disease. Author(s): DeRousseau CJ. Source: American Journal of Physical Anthropology. 1985 July; 67(3): 177-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4061576

•

Analgesic effect of etidronate on degenerative joint disease. Author(s): Fujita T, Fujii Y, Okada SF, Miyauchi A, Takagi Y. Source: Journal of Bone and Mineral Metabolism. 2001; 19(4): 251-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448018

•

Animal models of degenerative joint disease. Author(s): Adams ME, Billingham ME. Source: Curr Top Pathol. 1982; 71: 265-97. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7116952

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•

Approaches to the patient with degenerative joint disease. Author(s): Hardin JG. Source: Mod Treat. 1971 November; 8(4): 840-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5159965

•

Arthroplasty of the first metatarsophalangeal joint with a double-stem silicone implant. Results in patients who have degenerative joint disease failure of previous operations, or rheumatoid arthritis. Author(s): Cracchiolo A 3rd, Weltmer JB Jr, Lian G, Dalseth T, Dorey F. Source: The Journal of Bone and Joint Surgery. American Volume. 1992 April; 74(4): 55263. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1583050

•

Arthroplasty of the hip for idiopathic degenerative joint disease. Author(s): Ivins JC, Benson WF, Bickel WH, Nelson JW. Source: Surg Gynecol Obstet. 1967 December; 125(6): 1281-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6065265

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Arthroscopic treatment of degenerative joint disease of the knee. Author(s): Gross DE, Brenner SL, Esformes I, Gross ML. Source: Orthopedics. 1991 December; 14(12): 1317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1784548

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Biochemical aspects of degenerative joint disease. Author(s): Chrisman OD. Source: Clinical Orthopaedics and Related Research. 1969 May-June; 64: 77-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4183117

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Blood salicylate levels and clinical trials with a new form of enteric-coated aspirin: studies in rheumatoid arthritis and degenerative joint disease. Author(s): Baum J. Source: J Clin Pharmacol J New Drugs. 1970 March-April; 10(2): 132-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4906542

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Bone scan evaluation of degenerative joint disease of the spine. Author(s): Lin DS, Alavi A. Source: Int J Nucl Med Biol. 1982; 9(1): 63-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6211413

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•

Boundary lubricating ability of synovial fluid in degenerative joint disease. Author(s): Davis WH Jr, Lee SL, Sokoloff L. Source: Arthritis and Rheumatism. 1978 September-October; 21(7): 754-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=697946

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Cartilage structure and metabolism and basic changes in degenerative joint disease. Author(s): Muir H. Source: Aust N Z J Med. 1978; 8 Suppl 1: 1-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=365155

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Chronic repetitive trauma: a cause of atypical degenerative joint disease. Author(s): Hellmann DB, Helms CA, Genant HK. Source: Skeletal Radiology. 1983; 10(4): 236-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6648561

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Clinical comparative study of microcurrent electrical stimulation to mid-laser and placebo treatment in degenerative joint disease of the temporomandibular joint. Author(s): Bertolucci LE, Grey T. Source: Cranio. 1995 April; 13(2): 116-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8697497

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Comparative degenerative joint disease of the vertebral column in the medieval monastic cemetery of the Gilbertine priory of St. Andrew, Fishergate, York, England. Author(s): Knusel CJ, Goggel S, Lucy D. Source: American Journal of Physical Anthropology. 1997 August; 103(4): 481-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9292166

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Comparison of skeletal and dental morphology in asymptomatic volunteers and symptomatic patients with bilateral degenerative joint disease. Author(s): Gidarakou IK, Tallents RH, Kyrkanides S, Stein S, Moss M. Source: Angle Orthod. 2003 February; 73(1): 71-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607858

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Compositional changes of glycosaminoglycans of the human menisci with age and degenerative joint disease. Author(s): Karube S, Shoji H. Source: Nippon Seikeigeka Gakkai Zasshi. 1982 January; 56(1): 51-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6896062

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Conventional total hip arthroplasty for degenerative joint disease in patients between the ages of forty and sixty years. Author(s): Ranawat CS, Atkinson RE, Salvati EA, Wilson PD Jr. Source: The Journal of Bone and Joint Surgery. American Volume. 1984 June; 66(5): 74552. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6725322

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Correlates with comfort and function after total shoulder arthroplasty for degenerative joint disease. Author(s): Matsen FA 3rd, Antoniou J, Rozencwaig R, Campbell B, Smith KL. Source: Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons. [et Al.]. 2000 November-December; 9(6): 465-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11155297

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Correlation of radiographic and arthroscopic findings with rotator cuff tears and degenerative joint disease. Author(s): Umans HR, Pavlov H, Berkowitz M, Warren RF. Source: Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons. [et Al.]. 2001 September-October; 10(5): 428-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11641699

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Current concepts of degenerative joint disease (osteoarthritis). Author(s): Moskowitz RW, Klein L, Mast WA. Source: Bulletin on the Rheumatic Diseases. 1967 May; 17(9): 459-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6073878

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Degenerative joint disease among populations in Wensleydale, England and Jamaica. Author(s): Lawrence JS, Molyneux M. Source: International Journal of Biometeorology. 1968 May; 12(2): 163-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5678437

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Degenerative joint disease in a Jamaican rural population. Author(s): Bremner JM, Lawrence JS, Miall WE. Source: Annals of the Rheumatic Diseases. 1968 July; 27(4): 326-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5666672

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Degenerative joint disease in African great apes: an evolutionary perspective. Author(s): Jurmain R. Source: Journal of Human Evolution. 2000 August; 39(2): 185-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968928

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Degenerative joint disease in ballet dancers. Author(s): Andersson S, Nilsson B, Hessel T, Saraste M, Noren A, Stevens-Andersson A, Rydholm D. Source: Clinical Orthopaedics and Related Research. 1989 January; (238): 233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2910606

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Degenerative joint disease in female ballet dancers. Author(s): van Dijk CN, Lim LS, Poortman A, Strubbe EH, Marti RK. Source: The American Journal of Sports Medicine. 1995 May-June; 23(3): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7661255

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Degenerative joint disease in hunter-gatherers and agriculturalists from the Southeastern United States. Author(s): Bridges PS. Source: American Journal of Physical Anthropology. 1991 August; 85(4): 379-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1928312

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Degenerative joint disease in the hip and spine. Author(s): Saunders WA, Gleeson JA, Timlin DM, Preston TD, Brewerton DA. Source: Rheumatol Rehabil. 1979 August; 18(3): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=493800

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Degenerative joint disease in weight-lifters. Fact or fiction? Author(s): Fitzgerald B, McLatchie GR. Source: British Journal of Sports Medicine. 1980 July; 14(2-3): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7407459

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Degenerative joint disease of the hands. Author(s): Fernandez-Herlihy L. Source: Lahey Clin Found Bull. 1969 January-March; 18(1): 35-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5767146

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Degenerative joint disease of the lumbar spine in coal miners--a clinical and x-ray study. Author(s): Caplan PS, Freedman LM, Connelly TP. Source: Arthritis and Rheumatism. 1966 October; 9(5): 693-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4224519

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Degenerative joint disease of the trapezium: a comparative radiographic and anatomic study. Author(s): North ER, Eaton RG. Source: The Journal of Hand Surgery. 1983 March; 8(2): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6833724

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Degenerative joint disease on MRI and physical activity: a clinical study of the knee joint in 320 patients. Author(s): Bachmann GF, Basad E, Rauber K, Damian MS, Rau WS. Source: European Radiology. 1999; 9(1): 145-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9933399

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Degenerative joint disease. Author(s): Buckwalter JA, Martin J. Source: Clin Symp. 1995; 47(2): 1-32. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7554763

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Degenerative joint disease. Author(s): Calin A. Source: American Family Physician. 1986 January; 33(1): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3942044

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Degenerative joint disease. Author(s): Altman RD, Hochberg MC. Source: Clin Rheum Dis. 1983 December; 9(3): 681-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6360521

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Degenerative joint disease. Comparative aspects of osteoarthritis of the hip in man. Author(s): Murray RO. Source: The Journal of Small Animal Practice. 1971 February; 12(2): 99-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5551927

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Degenerative joint disease. Part I: Diagnosis and management considerations. Author(s): Bates RE Jr, Gremillion HA, Stewart CM. Source: Cranio. 1993 October; 11(4): 284-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8118899

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Degenerative joint disease. Part II: Symptoms and examination findings. Author(s): Bates RE Jr, Gremillion HA, Stewart CM. Source: Cranio. 1994 April; 12(2): 88-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8055593

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Degenerative joint disease: cartilage or vascular disease? Author(s): Imhof H, Breitenseher M, Kainberger F, Trattnig S. Source: Skeletal Radiology. 1997 July; 26(7): 398-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259096

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Diagnostic accuracy of TMJ vibration analysis for internal derangement and/or degenerative joint disease. Author(s): Ishigaki S, Bessette RW, Maruyama T. Source: Cranio. 1994 October; 12(4): 241-5; Discussion 246. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7828206

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Diclofenac concentrations in synovial fluid and plasma after cutaneous application in inflammatory and degenerative joint disease. Author(s): Radermacher J, Jentsch D, Scholl MA, Lustinetz T, Frolich JC. Source: British Journal of Clinical Pharmacology. 1991 May; 31(5): 537-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1888621

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Double-blind comparison of etodolac SR and diclofenac SR in the treatment of patients with degenerative joint disease of the knee. Author(s): Khan FM, Williams PI. Source: Current Medical Research and Opinion. 1992; 13(1): 1-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1468239

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Early degenerative joint disease simulating impingement syndrome: arthroscopic findings. Author(s): Ellman H, Harris E, Kay SP. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 1992; 8(4): 482-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1466709

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Early effectiveness of shoulder arthroplasty for patients who have primary glenohumeral degenerative joint disease. Author(s): Matsen FA 3rd. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 February; 78(2): 260-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8609117

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Effects of retinacular release and tibial tubercle elevation in patellofemoral degenerative joint disease. Author(s): Lewallen DG, Riegger CL, Myers ER, Hayes WC. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 1990 November; 8(6): 856-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2213343

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Efficacy and tolerability of etodolac in aged patients affected by degenerative joint disease (osteoarthritis) in its active phase. Author(s): Todesco S, Del Ross T, Marigliano V, Ariani A. Source: Int J Clin Pharmacol Res. 1994; 14(1): 11-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7927957

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Etodolac, aspirin, and placebo in patients with degenerative joint disease: a twelveweek study. Author(s): Andelman SY. Source: Clinical Therapeutics. 1983; 5(6): 651-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6226358

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European double-blind multicenter study comparing isoxicam and indomethacin in treatment of degenerative joint disease. Author(s): Jessop JD, Evans DP. Source: The American Journal of Medicine. 1985 October 18; 79(4B): 24-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3904435

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Expression of basic fibroblast growth factor in synovial tissue from patients with rheumatoid arthritis and degenerative joint disease. Author(s): Qu Z, Huang XN, Ahmadi P, Andresevic J, Planck SR, Hart CE, Rosenbaum JT. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1995 September; 73(3): 339-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7564266

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Extensive hemosiderin deposition in the medial meniscus of a knee. Its possible relationship to degenerative joint disease. Author(s): Bennett GL, Leeson MC, Michael A. Source: Clinical Orthopaedics and Related Research. 1988 May; (230): 182-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3284676

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Glucosamine, chondroitin, and manganese ascorbate for degenerative joint disease of the knee or low back: a randomized, double-blind, placebo-controlled pilot study. Author(s): Leffler CT, Philippi AF, Leffler SG, Mosure JC, Kim PD. Source: Military Medicine. 1999 February; 164(2): 85-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10050562

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High resolution computed tomography of the cadaveric sternoclavicular joint: findings in degenerative joint disease. Author(s): Baker ME, Martinez S, Kier R, Wain S. Source: J Comput Tomogr. 1988 January; 12(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3349794

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Idiopathic adolescent scoliosis--a prototype of degenerative joint disease. The relation of biomechanic factors to osteophyte formation. Author(s): Richter DE, Nash CL Jr, Moskowitz RW, Goldberg VM, Rosner IA. Source: Clinical Orthopaedics and Related Research. 1985 March; (193): 221-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3971628

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Immunohistochemical localization of metallothionein in synovial tissue of patients with chronic inflammatory and degenerative joint disease. Author(s): Backman JT, Siegle I, Fritz P. Source: Virchows Archiv : an International Journal of Pathology. 1998 August; 433(2): 153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9737793

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Inflammatory synovitis in degenerative joint disease. Author(s): Goldenberg DL, Egan MS, Cohen AS. Source: The Journal of Rheumatology. 1982 March-April; 9(2): 204-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7097678

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Influence of degenerative joint disease on spinal bone mineral measurements in postmenopausal women. Author(s): Yu W, Gluer CC, Fuerst T, Grampp S, Li J, Lu Y, Genant HK. Source: Calcified Tissue International. 1995 September; 57(3): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8574931

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Inter-examiner reliability of the diagnosis of cervical pillar hyperplasia (CPH) and the correlation between CPH and spinal degenerative joint disease (DJD). Author(s): Stupar M, Mauron D, Peterson CK. Source: Bmc Musculoskeletal Disorders [electronic Resource]. 2003 December 17; 4(1): 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678560

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Is running associated with degenerative joint disease? Author(s): Panush RS, Schmidt C, Caldwell JR, Edwards NL, Longley S, Yonker R, Webster E, Nauman J, Stork J, Pettersson H. Source: Jama : the Journal of the American Medical Association. 1986 March 7; 255(9): 1152-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3945034

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Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Author(s): Caruso I, Pietrogrande V. Source: The American Journal of Medicine. 1987 November 20; 83(5A): 66-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3318442

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Laboratory diagnosis of degenerative joint disease. Author(s): Schumacher HR Jr. Source: Ann Clin Lab Sci. 1975 July-August; 5(4): 242-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1163990

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Lipid metabolism in patients with degenerative joint disease. Author(s): Barwik-Schramm A, Kieta-Fyda A. Source: Pol Med J. 1966; 5(3): 515-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5920264

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Meclofenamate sodium in the treatment of degenerative joint disease of the hand (Heberden nodes). Author(s): Seiler V. Source: Arzneimittel-Forschung. 1983; 33(4A): 656-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6349652

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Meclofenamate sodium, phenylbutazone, and naproxen in the treatment of degenerative joint disease. Report of a placebo-controlled double-blind clinical comparison. Author(s): Lopez Sanchez J, Yanez Marchena G. Source: Arzneimittel-Forschung. 1983; 33(4A): 653-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6349651

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Noncollagenous proteins in cartilage of normal subjects and patients with degenerative joint disease. A gel electrophoretic study. Author(s): Chaminade F, Stanescu V, Stanescu R, Maroteaux P, Peyron JG. Source: Arthritis and Rheumatism. 1982 September; 25(9): 1078-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7126292

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Orgotein: a new anti-inflammatory metalloprotein drug: preliminary evaluation of clinical efficacy and safety in degenerative joint disease. Author(s): Lund-Olesen K, Menander KB. Source: Curr Ther Res Clin Exp. 1974 July; 16(7): 706-17. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4210460

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Pathogenesis of degenerative joint disease in the human temporomandibular joint. Author(s): Haskin CL, Milam SB, Cameron IL. Source: Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists. 1995; 6(3): 248-77. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8785264

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Pathologic quiz: degenerative joint disease. Author(s): Fechner RE, Card GG. Source: Arch Otolaryngol. 1978 December; 104(12): 742-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=718535

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Patient self-assessment of health status and function in glenohumeral degenerative joint disease. Author(s): Matsen FA 3rd, Ziegler DW, DeBartolo SE. Source: Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons. [et Al.]. 1995 September-October; 4(5): 345-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8548437

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Pedicle marrow signal intensity changes in the lumbar spine: a manifestation of facet degenerative joint disease. Author(s): Morrison JL, Kaplan PA, Dussault RG, Anderson MW. Source: Skeletal Radiology. 2000 December; 29(12): 703-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271551

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Periosteal and vascular innervation of the human patella in degenerative joint disease. Author(s): Badalamente MA, Cherney SB. Source: Seminars in Arthritis and Rheumatism. 1989 May; 18(4 Suppl 2): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2471271

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Phenylbutazone compared to piroxicam in symptomatic relief of degenerative joint disease. Author(s): Klinefelter HF. Source: The Journal of Rheumatology. 1988 June; 15(6): 1034-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3418629

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Pigmented villonodular synovitis-like lesions in association with rare cases of rheumatoid arthritis, osteonecrosis, and advanced degenerative joint disease. Report of five cases. Author(s): Vigorita VJ. Source: Clinical Orthopaedics and Related Research. 1984 March; (183): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6697577

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Primary glenohumeral degenerative joint disease: factors predisposing to arthroplasty. Author(s): Fardet L, Messow M, Maillefert JF, Dougados M. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673884

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Recent advances in hemophilia. Part V. Discussion paper: Degenerative joint disease. Author(s): Hilgartner MW. Source: Annals of the New York Academy of Sciences. 1975 January 20; 240: 340-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1053878

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Recreational activities and degenerative joint disease. Author(s): Panush RS, Inzinna JD. Source: Sports Medicine (Auckland, N.Z.). 1994 January; 17(1): 1-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8153496

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Rehabilitation of orthopedic and rheumatologic disorders. 3. Degenerative joint disease. Author(s): Brander VA, Kaelin DL, Oh TH, Lim PA. Source: Archives of Physical Medicine and Rehabilitation. 2000 March; 81(3 Suppl 1): S67-72; Quiz S78-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10721763

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Results of arthroscopic subacromial decompression in patients with subacromial impingement and glenohumeral degenerative joint disease. Author(s): Guyette TM, Bae H, Warren RF, Craig E, Wickiewicz TL. Source: Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons. [et Al.]. 2002 July-August; 11(4): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195244

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Role of roentgen therapy in management of degenerative joint disease. Author(s): Vi Gario GD, Wirka HW, Vermund H. Source: Wis Med J. 1965 December; 64(12): 459-64. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5857506

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Safety and efficacy of etodolac compared with piroxicam in patients with degenerative joint disease of the knee. Author(s): Dick WC, Bulstra S, Schardijn GH, Feenstra RM. Source: Clinical Therapeutics. 1992 July-August; 14(4): 517-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1388092

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Senescent pigmentation of cartilage and degenerative joint disease. Author(s): Van der Korst JK, Skoloff L, Miller EJ. Source: Arch Pathol. 1968 July; 86(1): 40-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5654578

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Serum copper and ceruloplasmin levels in rheumatoid arthritis and degenerative joint disease and their pharmacological implications. Author(s): Conforti A, Franco L, Menegale G, Milanino R, Piemonte G, Velo GP. Source: Pharmacol Res Commun. 1983 October; 15(9): 859-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6647528

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Severe degenerative joint disease. Mild and moderately severe hemophilia A. Author(s): Gilchrist GS, Hagedorn AB, Stauffer RN. Source: Jama : the Journal of the American Medical Association. 1977 November 28; 238(22): 2383-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=578865

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Six-week, double-blind, placebo-controlled and long-term, open-label multicenter study of isoxicam in treatment of degenerative joint disease. Author(s): Posner SL. Source: The American Journal of Medicine. 1985 October 18; 79(4B): 17-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3904434

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Solid-state temporomandibular joint imaging: accuracy in detecting osseous changes of degenerative joint disease and determining condylar spatial relations. Author(s): Scarfe WC, Farman AG, Silveira A, Fairbanks BW, Kelly PJ. Source: American Journal of Orthodontics and Dentofacial Orthopedics : Official Publication of the American Association of Orthodontists, Its Constituent Societies, and the American Board of Orthodontics. 2003 October; 124(4): 452-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560277

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Spondylolysis and its relationship to degenerative joint disease in the prehistoric southeastern United States. Author(s): Bridges PS. Source: American Journal of Physical Anthropology. 1989 July; 79(3): 321-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2669502

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Subchondral bone changes in patients with early degenerative joint disease. Author(s): Radin EL, Paul IL, Tolkoff MJ. Source: Arthritis and Rheumatism. 1970 July-August; 13(4): 400-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4246869

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Symptomatic degenerative joint disease. Report of a case. Author(s): Swintak EF, Schriver WR, Tsagaris GJ. Source: Oral Surg Oral Med Oral Pathol. 1976 December; 42(6): 722-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=63109

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Synovial fluid fatty acid composition in patients with rheumatoid arthritis, gout and degenerative joint disease. Author(s): Kim IC, Cohen AS. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1966 October; 123(1): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5924459

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Synovial fluid proteins in degenerative joint disease in dogs. Author(s): Strom H, Alexandersen S, Poulsen OM, Hau J. Source: Veterinary Immunology and Immunopathology. 1989 September; 22(2): 187-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2479164

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Synovial lymphocyte subsets in rheumatoid arthritis and degenerative joint disease. Author(s): Reidbord HE, Osial TA Jr. Source: The Journal of Rheumatology. 1987 December; 14(6): 1089-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2963911

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Synovial membrane histopathology in the differential diagnosis of rheumatoid arthritis, gout, pseudogout, systemic lupus erythematosus, infectious arthritis and degenerative joint disease. Author(s): Goldenberg DL, Cohen AS. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 1978 May; 57(3): 239-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=642792

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Temporomandibular degenerative joint disease in children and adolescents: report of eight cases. Author(s): Packota GV. Source: Dento Maxillo Facial Radiology. 1989 May; 18(2): 82-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2635123

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Temporomandibular degenerative joint disease. Part I. Anatomy, pathophysiology, and clinical description. Author(s): Kreutziger KL, Mahan PE. Source: Oral Surg Oral Med Oral Pathol. 1975 August; 40(2): 165-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1057144

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Temporomandibular degenerative joint disease. Part II. Diagnostic procedure and comprehensive management. Author(s): Kreutziger KL, Mahan PE. Source: Oral Surg Oral Med Oral Pathol. 1975 September; 40(3): 297-319. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=52135

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The biology of degenerative joint disease. Author(s): Sokoloff L. Source: Acta Rhumatol Belg. 1977 January-June; 1(1-2): 155-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=755359

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The correlation of comorbidity with function of the shoulder and health status of patients who have glenohumeral degenerative joint disease. Author(s): Rozencwaig R, van Noort A, Moskal MJ, Smith KL, Sidles JA, Matsen FA 3rd. Source: The Journal of Bone and Joint Surgery. American Volume. 1998 August; 80(8): 1146-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9730123

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The diagnosis and treatment of three chronic facial pain disorders: deafferentation neuralgia, degenerative joint disease of the temporomandibular joint, and myofascial syndrome. Author(s): Marbach JJ, Varoscak JR, Cloidt JC. Source: J Mass Dent Soc. 1986 Fall; 35(4): 169-72, 200-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3467007

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The effect of tolmetin on the chronic pain and decreased functional capacity associated with degenerative joint disease. Author(s): Amadio P Jr, Cummings DM. Source: Journal of Clinical Pharmacology. 1985 March; 25(2): 100-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3886706

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The effects of temporomandibular joint internal derangement and degenerative joint disease on tomographic and arthrotomographic images. Author(s): Brand JW, Whinery JG Jr, Anderson QN, Keenan KM. Source: Oral Surg Oral Med Oral Pathol. 1989 February; 67(2): 220-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2919068

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The magnitude and durability of functional improvement after total shoulder arthroplasty for degenerative joint disease. Author(s): Goldberg BA, Smith K, Jackins S, Campbell B, Matsen FA 3rd. Source: Journal of Shoulder and Elbow Surgery / American Shoulder and Elbow Surgeons. [et Al.]. 2001 September-October; 10(5): 464-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11641705

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The management of degenerative joint disease. Author(s): Leonard MH. Source: Southwest Med. 1969 September; 29(9): 145-54. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5351153

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The management of degenerative joint disease--an introduction. Author(s): Wright V. Source: Scand J Rheumatol Suppl. 1982; 43: 7-11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6953568

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The pattern of involvement of appendicular degenerative joint disease. Author(s): Jurmain RD. Source: American Journal of Physical Anthropology. 1980 July; 53(1): 143-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6998300

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The role of arthroscopy in ankle and subtalar degenerative joint disease. Author(s): Cheng JC, Ferkel RD. Source: Clinical Orthopaedics and Related Research. 1998 April; (349): 65-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9584368

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The torn meniscus, the torn anterior cruciate ligament, and their relationship to degenerative joint disease. Author(s): Casscells SW. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 1985; 1(1): 28-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4091906

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The trapezium-thumb metacarpal joint: the relationship of joint shape and degenerative joint disease. Author(s): North ER, Rutledge WM. Source: Hand. 1983 June; 15(2): 201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6884851

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Therapeutic activity, clinical and gastric tolerance of 20mg daily dose of droxicam in comparison with piroxicam in patients with degenerative joint disease. Author(s): Schuetz E, Sanchez J, Garcia-Barbal J, Sarti JF, Reuter C, Harrison FJ. Source: Eur J Rheumatol Inflamm. 1991; 11(4): 21-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1365486

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Tibiofemoral contact pressures in degenerative joint disease. Author(s): Riegger-Krugh C, Gerhart TN, Powers WR, Hayes WC. Source: Clinical Orthopaedics and Related Research. 1998 March; (348): 233-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9553558

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Tobacco use and degenerative joint disease of the spine. Author(s): Brotherson JD, Marshall ES, Measom G, Clark JR. Source: Journal of the American Academy of Nurse Practitioners. 2003 June; 15(6): 27781. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861894

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Usefulness of pinhole collimator in differential diagnosis of metastatic disease and degenerative joint disease in the vertebrae; evaluation by receiver operating characteristics (ROC) analysis. Author(s): Kosuda S, Kawahara S, Ishibashi A, Tamura K, Tsukatani Y, Fujii H, Kubo A, Hashimoto S. Source: Ann Nucl Med. 1989 November; 3(3): 119-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2641457

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Validation of the clinical diagnostic criteria for temporomandibular disorders for the diagnostic subgroup of degenerative joint disease. Author(s): Brandlmaier I, Gruner S, Rudisch A, Bertram S, Emshoff R. Source: Journal of Oral Rehabilitation. 2003 April; 30(4): 401-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12631164

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Vibration analysis of the temporomandibular joints with degenerative joint disease. Author(s): Ishigaki S, Bessette RW, Maruyama T. Source: Cranio. 1993 October; 11(4): 276-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8118898

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X-linked spondyloepiphyseal dysplasia tarda: molecular cause of a heritable disorder associated with early degenerative joint disease. Author(s): Fiedler J, Bergmann C, Brenner RE. Source: Acta Orthopaedica Scandinavica. 2003 December; 74(6): 737-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14763708

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CHAPTER 2. NUTRITION AND DEGENERATIVE JOINT DISEASE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and degenerative joint disease.

Finding Nutrition Studies on Degenerative Joint Disease 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 “degenerative joint disease” (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 information is typical of that found when using the “Full IBIDS Database” to search for “degenerative joint disease” (or a synonym): •

Articular chondrocytes from animals with a dermatan sulfate storage disease undergo a high rate of apoptosis and release nitric oxide and inflammatory cytokines: a possible mechanism underlying degenerative joint disease in the mucopolysaccharidoses. Author(s): Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA. [email protected] Source: Simonaro, C M Haskins, M E Schuchman, E H Lab-Invest. 2001 September; 81(9): 1319-28 0023-6837

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Effects of body mass and genotype on avian degenerative joint disease pathology and articular cartilage proteoglycan distribution. Author(s): Department of Biochemistry, University of Edinburgh, U.K. Source: Anderson MacKenzie, J M Hulmes, D J Thorp, B H Clin-Exp-Rheumatol. 1998 Jul-August; 16(4): 403-8 0392-856X

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Oral glycosaminoglycans in treatment of degenerative joint disease in horses. Source: Hanson, R.R. Equine-pract. Mission Viejo, CA : Veterinary Practice Publishing Company. Nov/December 1996. volume 18 (10) page 18-22. 0162-8941

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Oral treatment with a glucosamine-chondroitin sulfate compound for degenerative joint disease in horses: 25 cases. Source: Hanson, R.R. Smalley, L.R. Huff, G.K. White, S. Hammad, T.A. Equine-pract. Irvine, Calif.: Veterinary Practice Publishing Company. October 1997. volume 19 (9) page 16-20, 22. 0162-8941

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Use of Cosequin for the treatment of degenerative joint disease in a 7-year-old appaloosa. Source: Macleod, A. Turner, T. Lennox, T. Ferguson, S. Compend-contin-educ-pract-vet. Trenton, N.J. : Veterinary Learning Systems. Sept 2001. volume 23 (9) page 842-847. 0193-1903

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/

Nutrition

37

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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 degenerative joint disease; 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: •

Minerals Chondroitin Alternative names: chondroitin sulfate, sodium chondroitin sulfate Source: Integrative Medicine Communications; www.drkoop.com Glucosamine/chondroitin Source: Healthnotes, Inc.; www.healthnotes.com

•

Food and Diet Chondroitin Sulfate Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND DEGENERATIVE JOINT DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to degenerative joint disease. 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 degenerative joint disease 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 “degenerative joint disease” (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 degenerative joint disease: •

The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease. Author(s): Kelly GS. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1998 February; 3(1): 27-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600024

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 degenerative joint disease; 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 Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Temporomandibular Joint Dysfunction Source: Integrative Medicine Communications; www.drkoop.com TMJ Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Glucosamine Source: Integrative Medicine Communications; www.drkoop.com SAMe Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 41

SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html

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 DEGENERATIVE JOINT DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to degenerative joint disease. 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 “degenerative joint disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on degenerative joint disease, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Degenerative Joint Disease 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 degenerative joint disease. 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 pattern of involvement of degenerative joint disease between an agricultural and non-agricultural skeletal series (Averbuch, Indian Knoll) by PIERCE, LORNA KATHRYN COLLINS, PHD from THE UNIVERSITY OF TENNESSEE, 1987, 333 pages http://wwwlib.umi.com/dissertations/fullcit/8810387

•

Patterns of degenerative joint disease in Middle Woodland, Late Woodland, and Mississippian skeletal series from the Lower Illinois Valley by PICKERING, ROBERT BRUCE, PHD from NORTHWESTERN UNIVERSITY, 1984, 260 pages http://wwwlib.umi.com/dissertations/fullcit/8411176

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Skeletal asymmetry, degenerative joint disease and handedness in humans by Czuzak, Maria Helen, PhD from THE UNIVERSITY OF ARIZONA, 1998, 236 pages http://wwwlib.umi.com/dissertations/fullcit/9829389

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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. PATENTS ON DEGENERATIVE JOINT DISEASE 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.8 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 “degenerative joint disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on degenerative joint disease, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Degenerative Joint Disease By performing a patent search focusing on degenerative joint disease, 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. 8Adapted

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 degenerative joint disease: •

Assay of YKL-40 as a marker for cancer Inventor(s): Johansen; Julia S. (Frederiksberg, DK), Price; Paul A. (La Jolla, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,579,684 Date filed: March 4, 1999 Abstract: This invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory or degenerative joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers. The figure shows the elution position of substantially pure serum YKL-40 on a gel filtration column. Excerpt(s): The invention relates to the identification of a circulating protein associated with extracellular fiber matrix metabolism in mammalian connective tissues. More specifically, it is directed to assays for the detection and quantitation of molecules and fragments of YKL-40, a protein associated with connective tissue metabolism in mammals. It also involves correlating serum levels of YKL-40 in a mammal to the presence and status of diseases in which matrix metabolism plays a role, such as joint disorders and the metastasis of certain tumors. The extracellular matrix of mammalian connective tissues (such as articular cartilage of joints and vascular wall tissue of the vascular and lymphatic system) provides strength to, and (to varying degrees) a barrier to the migration of cells from, the tissue. In certain disease processes, however, the matrix is degraded by hydrolytic enzymes. As the matrix degrades, the integrity of the tissue is impaired, which may allow tissue cells, by-products and other residues of the matrix metabolism to escape into bodily fluids and/or lymphatic or vascular circulation. Detection of these molecules and cells can, in certain instances, provide information regarding the biochemical characteristics of the extracellular matrix, including how it is synthesized and how it is lost. Also, where a particular molecule that is produced and/or secreted during abnormal matrix metabolism is closely related to a disease process, quantitation of that molecule in the patient's body fluids and/or tissues can help clinicians monitor the progress of the disease. Human joint cartilage is known to contain several different types of proteins and proteoglycans, a few of which are present only in cartilage. These matrix constituents are released from cartilage tissue as it degrades during the course of certain joint diseases. The quantity of released matrix constituents (including fragments thereof and related macromolecules) present in a particular fluid or tissue may correlate with the intensity of the disease. Conversely, where the damage to the cartilage is reversible (as in secondary reactive arthritis caused by infection of the joint tissue), a reduction in levels of previously measured released matrix constituents may correlate with the degree of remission of the disease. Web site: http://www.delphion.com/details?pn=US06579684__

Patents 47

•

Compositions to suppress gastric bleeding in indomethacin and phenylbutazone therapy Inventor(s): Alphin; Reevis Stancil (Richmond, VA), Droppleman; David Andrew (Richmond, VA) Assignee(s): A. H. Robins Company, Incorporated (Richmond, VA) Patent Number: 3,993,767 Date filed: November 18, 1975 Abstract: Methods of treating symptomatic conditions of inflammation due to chronic and acute rheumatic and degenerative joint disease with a combination of indomethacin or phenylbutazone and a phenoxymethyl-2-oxazolidinone resulting in beneficial reduction in side effects of ulceration and bleeding in the lower intestinal tract normally associated with indomethacin and phenylbutazone and compositions containing the combination are disclosed. Excerpt(s): This invention relates to novel methods, combinations, and compositions for controlling inflammation in the relief of symptomatic, chronic and acute rheumatic conditions. More particularly, the invention relates to combinations and compositions of indomethacin or phenylbutazone and phenoxymethyl-2-oxazolidinones and methods of using them to ameliorate the undesirable side effects of indomethacin or phenylbutazone in the gastrointestinal tract. Indomethacin and phenylbutazone are widely used for the therapy of inflammatory conditions associated with rheumatic diseases and/or arthritis. However, certain undesirable side effects are associated with the use of indomethacin and phenylbutazone in the gastrointestinal region, among which side effects are bleeding, ulceration, perforation of the intestines and occasionally death. The need to overcome the irritation, particularly in the lower gastrointestinal tract, caused by indomethacin and phenylbutazone is a matter of urgent concern, inasmuch as the walls of the intestine in the lower region are relatively thin and perforation may occur suddenly and without warning. The method of the present invention, having suitably overcome, by remedial action, the severe manifestation of ulceration and perforation in the lower GI tract normally associated with indomethacin and phenylbutazone therapy, is highly suited to the treatment of the symptomatic inflammatory effect in mammals and humans of diseases such as gouty arthritis, bursitis, rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis and the like. Indicative of the state of the art have been attempts to find combinations which would allow administration of indomethacin or phenylbutazone for their full therapeutic effect as anti-inflammatory drugs. Certain steroids such as spirolactone have shown protection against intestinal ulcers caused by indomethacin in rats [Can. J. Physiol. Pharmacol. 1969, 47 (12) 981-3]. Coprecipitates of lignosulfonate or tannic acid with indomethacin or phenylbutazone have shown reduced irritation on the stomach tissue of cats. [C. A. 78, P102009n and C. A. 79, P9873]. Pro-Bathine which is ammonium (2-hydroxyethyl)diisopropylmethylbromide, xanthine-9-carboxylate has shown reduced ulceration caused by indomethacin in the rat stomach [Arch. Int. Pharmacodyn. 191, 370-377 (1971)]. Web site: http://www.delphion.com/details?pn=US03993767__

48

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Method of treating degenerative joint disease by injection of meth(acrylamide) (co)polymers Inventor(s): Chylinski; Victoria S. (11 Peghouse Rise, Slad Road, Stroud, Glos., GB2), Trager; Seymour F. (14 Sherwood Dr., Plainview, NY 11803) Assignee(s): none reported Patent Number: 4,828,828 Date filed: July 28, 1987 Abstract: A method for the treatment of degenerative joint disease in a mammal suffering therefrom which includes administration by injection of an effective amount of a pharmaceutical composition into the arthritically afflicted joints of the mammal thereby lubricating and cushioning the joints. The composition includes acrylamide or methacrylamide polymers or copolymers thereof having a molecular weight from about 1 to about 15 million and a pharmaceutically acceptable diluent. Excerpt(s): Mammalian joints typically contain a small amount of synovial fluid which lubricates and moistens the joint surfaces to protect the joint against trauma, injury and degeneration. Some specific synovial fluid functions are to lubricate the joint surfaces, to absorb shocks to the joints, to bind acid and, possibly, to nourish some of the structural components of the joints. The synovial fluid is produced in the body by specialized cells, and the impairment of the fluid, i.e. decreased viscosity of the fluid due to the presence of degenerate cartilage products therein, is the principal source of the pain associated with degenerative joint diseases. As a result, various modes of intra-articular treatment of arthritis have been proposed. Commercially available compositions including corticosteroids such as triamcinoline, prednisolone and hydrocortisone acetate are now in use in arthritis treatment. However, these compositions are difficult to use due to difficulties in dosage determination. Also, a number of adverse reactions have been observed in intra-articular steroid therapy. Consequently, corticosteroid treatments have fallen into relative disuse. The use of hyaluronic acid has also been proposed for arthritis treatment. Hyaluronic acid appears to lubricate only the soft tissues of the joint which are not subject to heavy loading. Again, adverse side effects stemming from the treatment have been reported in some patients. Moreover, patients with clinical histories of local adverse reactions to the acid treatment appear susceptible to severe permanent joint damage. Web site: http://www.delphion.com/details?pn=US04828828__

•

Use of N-acetylglucosamine for the therapy of degenerative joint disease and related diseases Inventor(s): Speck; Ulrich (Benediktinerstrasse 50, D-1000 Berlin 28, DE) Assignee(s): none reported Patent Number: 4,870,061 Date filed: January 26, 1989 Abstract: The invention refers to the use of N-acetylglucosamine for the therapy of degenerative diseases of the joints and of the connective and the supporting tissues as well as for the therapy of related diseases, wherein the N-acetylglucosamine is administered to the body through buccal absorption.

Patents 49

Excerpt(s): The present invention refers to the use of N-acetylglucosamine for the therapy of degenerative diseases of the joints and of the connective and the supporting tissues as well as for the therapy of related diseases. Moreover, the invention comprises the use of N-acetylglucosamine for the production of drugs for corresponding therapies. Degenerative diseases of the joints (arthrosis) are widespread with human beings as well as with animals of middle and higher age. They are a frequent reason for poor general condition and limited ability to work. One main reason for these diseases is the destruction of glucosaminoglycanes (GAG) which are an essential component of the cartilage substances and of other flexible elements as well as a contributor to the lubrication of the joints. The therapy of these painful, partly inflammatory conditions often only takes place symptomatically with the aid of non-steroidal anti-inflammatory drugs such as, for instance, indomethacin, or even corticoids. Both groups of therapeuticals cause severe side effects and should therefore be used as little as possible. Moreover, the application of non-steroidal anti-inflammatory drugs and corticoids entails the danger of further shifting the metabolism of the GAGs in the direction of accelerated degradation. Thus, the advantages of momentary relief of the symptoms of the disease, such as pain and immobility of the joints, is--besides other risks--connected with the danger of an acceleration in the degenerative processes which cause the underlying disease. Web site: http://www.delphion.com/details?pn=US04870061__

Patent Applications on Degenerative Joint Disease As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to degenerative joint disease: •

ASSAY FOR YKL-40 AS A MARKER FOR DEGRADATION OF MAMMALLIAN CONNECTIVE TISSUE MATRICES Inventor(s): JOHANSEN, JULIA S.; (COPENHAGEN, DK), PRICE, PAUL A.; (LA JOLLA, CA) Correspondence: Law Offices OF Jonathan Alan Quine; P O Box 458; Alameda; CA; 94501 Patent Application Number: 20020090658 Date filed: March 4, 1999 Abstract: This invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory or degenerative joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers. The figure shows the elution position of substantially pure serum YKL-40 on a gel filtration column.

9 This

has been a common practice outside the United States prior to December 2000.

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Degenerative Joint Disease

Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 08/089,989, filed on Jul. 9, 1993, now abandoned. The invention relates to the identification of a circulating protein associated with extracellular fiber matrix metabolism in mammalian connective tissues. More specifically, it is directed to assays for the detection and quantitation of molecules and fragments of YKL-40, a protein associated with connective tissue metabolism in mammals. It also involves correlating serum levels of YKL-40 in a mammal to the presence and status of diseases in which matrix metabolism plays a role, such as joint disorders and the metastasis of certain tumors. The extracellular matrix of mammalian connective tissues (such as articular cartilage of joints and vascular wall tissue of the vascular and lymphatic system) provides strength to, and (to varying degrees) a barrier to the migration of cells from, the tissue. In certain disease processes, however, the matrix is degraded by hydrolytic enzymes. As the matrix degrades, the integrity of the tissue is impaired, which may allow tissue cells, by-products and other residues of the matrix metabolism to escape into bodily fluids and/or lymphatic or vascular circulation. Detection of these molecules and cells can, in certain instances, provide information regarding the biochemical characteristics of the extracellular matrix, including how it is synthesized and how it is lost. Also, where a particular molecule that is produced and/or secreted during abnormal matrix metabolism is closely related to a disease process, quantitation of that molecule in the patient's body fluids and/or tissues can help clinicians monitor the progress of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition and method for treatment and prevention of traumatic synovitis and damage to articular cartilage Inventor(s): Marcum, Frank D.; (Lexington, KY) Correspondence: Stockwell & Associates, Psc; 861 Corporate Drive, Suite 201; Lexington; KY; 40503; US Patent Application Number: 20040092479 Date filed: October 16, 2003 Abstract: The invention provides compositions useful for the treatment and/or prevention of damage to diarthrodial (synovial) joints and, in particular, traumatic synovitis, inflammation of the synovial membrane, and damage to the articular cartilage of the joint. Specifically, provided are compositions specially formulated for intraarticular and/or parenteral use in the treatment and/or prevention of traumaticsynovitis and/or damage to articular cartilage. Compositions adapted specifically for post surgical joint lavage or treatment and/or prevention of inflammatory arthritis, osteoarthritis (OA) and/or degenerative joint disease (DJD) are also provided. Compositions adapted for intra-articular and/or systemic administration comprised of therapeutic amounts of: chondroitin sulfate; N-acetyl D-glucosamine; and hyaluronan (hyaluronic acid) are provided. Excerpt(s): This patent application claims the benefit of priority in provisional application Serial No. 60/419,009 filed on Oct. 16, 2002 and provisional application Serial No. 60/487,681 filed on Jul. 16, 2003. The present invention is generally directed to compositions useful for the treatment and/or prevention of damage to diarthrodial (synovial) joints and, in particular traumatic synovitis, inflammation of the synovial membrane, and damage to the articular cartilage of the joint. Specifically, the invention relates to compositions specially formulated for intra-articular and parenteral use in the treatment and/or prevention of traumatic synovitis and damage to articular cartilage,

Patents 51

e.g., for post surgical joint lavage or treatment and/or prevention of inflammatory arthritis, osteoarthritis (OA) and/or degenerative joint disease (DJD). Diarthrodial or synovial joints allow movement and transfer of load between bones. These two critical functions play a major role in athletic performance and disease or injury of these joints, in turn, has a major impact on athletic performance in man and in animals. For example, one of the most important causes of lameness among equine athletes is primary joint disease of the diathrodial or synovial joints. In the past 25 years much knowledge has been gained regarding the treatment and/or prevention of disease processes affecting synovial joints and, in particular, in the understanding of disease and trauma of articular cartilage (see, Mcllwraith & Trotter, "JOINT DISEASE IN THE HORSE", W. B. Saunders, 1996 (ISBN 0-7216-5135-6)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Surface electrical stimulation for increasing the quality and quantity of synovial fluid in joints Inventor(s): Carroll, William J.; (Sedro Woolley, WA), Terrell, Richard M.; (Vancouver, WA) Correspondence: Blank Rome Llp; 600 New Hampshire Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20040054379 Date filed: September 11, 2003 Abstract: An electro-medical device and method for improving synovial fluid at a body segment having a joint by applying surface electrical stimulation using surface skin electrodes to the body segment. The electrical stimulation to the body segment and joint may be continuous or in a sequencing pattern. When the electrical stimulation uses a sequencing pattern, it mimics normal electrical sequencing of surrounding muscle of the joint during normal functioning activity. Surface electrical stimulation improves synovial fluid of the body segment and joint and ameliorates degenerative joint disease and osteoarthritis. Excerpt(s): Surface Electrical Stimulation (SES) has a beneficial effect on the production and quality of the synovium and the resultant synovial fluid. Electrical stimulation increases blood flow to stimulated areas (U.S. Pat. No. 6,393,328). However, the effect of SES on synovial fluid output and quality and on cartilage and joint deterioration has not been demonstrated or quantified. There is a need to demonstrate that SES has a beneficial effect on decreasing the progressive process of joint deterioration. Thus, there is a unaddressed need in the industry to demonstrate the beneficial effects of SES for the treatment and ameloriation of osteoarthritis and degenerative joint disease of, but not limited to, the hips, knees, ankles, toes, back, neck, and shoulders. Embodiments of the present invention provide an electro-medical device and method for improving synovial fluid at a body segment having a joint by applying surface electrical stimulation, using surface skin electrodes, to the body segment. The present invention utilizes surface electrical stimulation via surface skin electrodes to pass various types of current across the skin, or transcutaneously, wherein the surface skin electrodes are placed on the surface of the skin. Examples of this type of stimulation include, but are not limited to, Transcutaneous Electrical Never Stimulation (TENS), neuromuscular Electrical Stimulation (NMES), interferential stimulation, diadynamic stimulation, High Volt Galvanic Stimulation (HVGS), Electro-Magnetic and Pulsed Electro-Magnetic Field stimulation (EMF) and (PEMF) and, micro-current stimulation. Those types of surface

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electrical stimulation can be applied in a continuous manner or they may be applied in patterns of stimulation that mimic the natural functioning of the affected joint. 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 degenerative joint disease, 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 “degenerative joint disease” (or 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 degenerative joint disease. You can also use this procedure to view pending patent applications concerning degenerative joint disease. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

53

CHAPTER 6. BOOKS ON DEGENERATIVE JOINT DISEASE Overview This chapter provides bibliographic book references relating to degenerative joint disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on degenerative joint disease include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Chapters on Degenerative Joint Disease In order to find chapters that specifically relate to degenerative joint disease, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and degenerative joint disease 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 “degenerative joint disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on degenerative joint disease: •

Osteoarthrosis/Osteoarthritis Source: in Zarb, G.A., et al. Temporomandibular Joint and Masticatory Muscle Disorders. Copenhagen, Denmark: Munksgaard. 1994. p. 298-314. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK 1016 Copenhagen K, Denmark. Phone Number: 45 33 12 70 30; Fax: 45 33 12 93 87. PRICE: DDK1456.00. Contact publisher directly for current price in U.S. Dollars. ISBN: 8716106377. Summary: This chapter on degenerative joint disease (osteoarthrosis and osteoarthritis, or OA) is from a comprehensive textbook that addresses temporomandibular joint disorders (TMD) and masticatory muscle disorders. Topics include definitions and general features, the prevalence of OA, etiology, pathogenesis, diagnostic considerations, and treatment. OA is defined as a primarily non-inflammatory pattern of reaction of movable joints to injury. The disease process is characterized by deterioration

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and abrasion of articular cartilage and soft tissue surfaces, and the occurrence of thickening and remodelling of the underlying bone and formation of marginal spurs and subarticular 'cysts.' The temporomandibular (TMJ) is one joint that can be affected by OA. The authors note that non-drug treatment strives to reduce joint overload so that healing can occur; consequently, rest and exercise are regarded as an important part of a self care strategy. Reversible dental interventions such as appliance therapy or restoration of posterior occlusal support may produce long-range benefits, although this has not yet been conclusively shown in clinical trials. The clinical long-term prognosis of TMJ OA is usually extremely favorable in spite of regularly observed severe radiographic changes. 5 figures. 2 tables. 40 references. (AA-M).

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APPENDICES

57

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 Institute10: •

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

•

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/

10

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

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

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.11 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:12 •

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

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

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

•

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/

•

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

11

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). 12 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

•

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 NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “degenerative joint disease” (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 24382 284 537 48 44 25295

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “degenerative joint disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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.

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Coffee Break: Tutorials for Biologists18 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 used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 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.20 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/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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. 20 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 degenerative joint disease 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 degenerative joint disease. 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 degenerative joint disease. 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 “degenerative joint disease”:

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Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Hip Injuries and Disorders http://www.nlm.nih.gov/medlineplus/hipinjuriesanddisorders.html Knee Injuries and Disorders http://www.nlm.nih.gov/medlineplus/kneeinjuriesanddisorders.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/tutorials/osteoarthritisloader.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html

Within the health topic page dedicated to degenerative joint disease, the following was listed: •

Diagnosis/Symptoms Guide to Lab Tests Source: Arthritis Foundation http://www.arthritis.org/conditions/lab_tests/labtestmain.asp Radiography (X-ray) - Bone Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/bone_radiography.htm

•

Treatment 2004 Drug Guide Source: Arthritis Foundation http://www.arthritis.org/conditions/DrugGuide/default.asp Arthritic Disorders and Treatments Source: American College of Foot and Ankle Surgeons http://www.acfas.org/brarthdis.html Arthroscopic Surgery Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/surgerycenterflash/arthrosco py.html Help Your Arthritis Treatment Work http://www.fda.gov/opacom/lowlit/arthrtis.html Injections Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=PN00046 Make No Mistake: Be Your Own Safety Net Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2003_archives/2003_05_06_ma ke_no_mistake_safetynet.asp

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Revision Hip Surgery Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/surgerycenterflash/revhip.ht ml Total Hip Replacement Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/surgerycenterflash/totalhip.ht ml Total Knee Replacement Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/booklet/thr_report.cfm?thread_id=9&topcategory=knee Total Knee Replacement Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/surgerycenterflash/totalknee. html Total Shoulder Replacement Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/surgerycenterflash/totalshoul der.html Types of Surgery Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/types.asp Unicondylar Knee Resurfacing Source: Arthritis Foundation http://www.arthritis.org/conditions/surgerycenter/surgerycenterflash/uni.html Viscosupplementation Treatment for Arthritis Source: American Academy of Orthopaedic Surgeons http://orthoinfo.aaos.org/fact/thr_report.cfm?Thread_ID=245&topcategory=Knee •

Alternative Therapy Acupuncture Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2000_archives/2000_05_06_acu puncture.asp Ayurvedic Herbs Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/1999_archives/1999_05_06expl orations.asp Complementary and Alternative Arthritis Treatments Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01121 Glucosamine and Chondroitin Sulfate Source: Arthritis Foundation http://www.arthritis.org/conditions/alttherapies/glucosamine.asp

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Homeopathy Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2000_archives/2000_03_04_ho meopathy.asp Meditation Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2001_archives/2001_01_02_me ditation.asp Tai Chi Source: Arthritis Foundation http://www.arthritis.org/resources/arthritistoday/2000_archives/2000_07_08_taic hi.asp •

From the National Institutes of Health Arthritis Advice Source: National Institute on Aging http://www.niapublications.org/engagepages/arthritis.asp Do I Have Arthritis? http://www.niams.nih.gov/hi/topics/arthritis/tengo/english.htm Handout on Health: Osteoarthritis Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/oahandout.htm Questions and Answers about Arthritis and Rheumatic Disease Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/arthritis/artrheu.htm

•

Latest News Diet, Exercise, and Osteoarthritis Source: 05/06/2004, American College of Rheumatology http://www.rheumatology.org/press/2004/dietOA0504.asp?aud=prs Osteoarthritis of the Hand and the Impact of Chopsticks Source: 05/06/2004, American College of Rheumatology http://www.rheumatology.org/press/2004/handOA0504.asp?aud=prs Surprising New Evidence about Adverse Effects of Vitamin C on Arthritis Source: 06/04/2004, American College of Rheumatology http://www.rheumatology.org/press/2004/vitc0604.asp?aud=prs Thermal Scans Used to Spot Osteoarthritis Source: 07/12/2004, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_18914 .html

•

Organizations American College of Rheumatology http://www.rheumatology.org/

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Arthritis Foundation http://www.arthritis.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ •

Prevention/Screening 10 Ways You Can Protect Your Joints Source: Arthritis Foundation http://www.arthritis.org/conditions/tips_jointprotection.asp

•

Research African Americans More Likely to Suffer From Severe Osteoarthritis of the Knee Source: American College of Rheumatology http://www.rheumatology.org/press/2003/pr11.asp Association of Bone Marrow Changes with Worsening of Knee Osteoarthritis Source: American College of Physicians http://www.annals.org/cgi/content/full/139/5_Part_1/I-33 Common Antibiotic Shows Promise for Treating Knee Osteoarthritis Source: American College of Rheumatology http://www.rheumatology.org/press/2003/pr27.asp Delivering on the Promise in Osteoarthritis Source: Arthritis Foundation http://www.arthritis.org/research/research_program/Osteoarthritis/default.asp Diet, Exercise, and Osteoarthritis Source: American College of Rheumatology http://www.rheumatology.org/press/2004/dietOA0504.asp?aud=prs Enrollment Begins for Osteoarthritis Initiative Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/mar2004/niams-17.htm Gastrointestinal Side Effects of Rofecoxib and Naproxen Source: American College of Physicians http://www.annals.org/cgi/content/full/139/7/I-29 Leeches to Treat Knee Osteoarthritis Source: American College of Physicians http://www.annals.org/cgi/content/full/139/9/I-22 OA Biomarkers Network: A New Way to Study Disintegrating Joints Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ne/highlights/spotlight/2004/oa_biomarkers.htm Osteoarthritis of the Hand and the Impact of Chopsticks Source: American College of Rheumatology http://www.rheumatology.org/press/2004/handOA0504.asp?aud=prs Promising New Therapy May Help Those with Osteoarthritis of the Knee Source: American College of Rheumatology http://www.rheumatology.org/press/2003/pr7.asp

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Scientists Identify Two Key Risk Factors for Hip Replacement in Women Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ne/highlights/spotlight/2003/hiprep.htm Scientists to Examine Influences of Biomechanics in Osteoarthritis Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ne/highlights/spotlight/2003/biomech.htm Surprising New Evidence about Adverse Effects of Vitamin C on Arthritis Source: American College of Rheumatology http://www.rheumatology.org/press/2004/vitc0604.asp?aud=prs 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 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 degenerative joint disease. 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: •

TMD: Temporomandibular Disorders Source: Bethesda, MD: National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH). 1996. 16 p. Contact: Available from National Oral Health Information Clearinghouse (NOHIC). 1 NOHIC Way, Bethesda, MD 20892-3500. (301) 402-7364. Fax (301) 907-8830. E-mail: [email protected]. Website: www.nohic.nidcr.nih.gov. PRICE: Single copy free; bulk orders available. NIH Publication No. 96-3487. Order Number OP-23. Summary: Temporomandibular disorders (TMD) is not just one disorder, but a group of conditions that affect the jaw joint and the muscles that control chewing. This brochure discusses TMD and reviews current medical research in this area. Topics include the anatomy of the temporomandibular joint itself; three main categories of TMD, including myofascial pain, internal derangement of the joint, and degenerative joint disease; the causes of TMD; TMD signs and symptoms; diagnosing TMD; treatment options; and recommendations for readers who think they might have TMD. The brochure stresses the importance of conservative treatment of TMD.

•

Temporomandibular Joint Dysfunction and Its Relationship to the Fibromyalgia Patient Source: Washington, DC: Fibromyalgia Association of Greater Washington. 1994. [2 p.].

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Contact: Available from Fibromyalgia Association of Greater Washington (FMAGW). 13203 Valley Drive, Woodbridge, VA 22191. (703) 790-2324. PRICE: Single copy free. Summary: This brochure outlines the relationship of temporomandibular joint dysfunction (TMD) and fibromylagia syndrome. The brochure stresses that TMD is a complex problem even for the otherwise healthy patient, but when it is combined with the multiple symptoms of a patient with fibromyalgia syndrome, it becomes difficult to diagnose and treat effectively without a team approach involving multiple disciplines. Because of the intricate neural pathways in and around the TM join and reflex referral arcs to far distant areas, the picture of TMD becomes complex when it is combined with the symptoms of fibromyalgia. The causes of TMD are varied and may include trauma, loss of teeth, improperly fitted dental appliances, improper orthodontic therapy, a variety of degenerative joint disease, growth and developmental problems, tumors, and bruxism (toothgrinding). Treatment ranges from simple appliance therapy along with warm, moist compresses, a soft diet and anti-inflammatory medication, to a multidisciplinary approach involving special x-rays, computerized measurement of jaw and muscle relationships and function, and specialized appliances along with physical therapy, and rheumatological evaluation. The brochure concludes that a dentist specializing in TMD or MPD (myofascial pain dysfunction) is necessary to determine the most appropriate therapy for each patient based on the presentation, severity, and dimensions of his or her symptoms and the nature of the problems present. 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 “degenerative joint disease” (or synonyms). The following was recently posted: •

Diagnosis and treatment of adult degenerative joint disease (DJD) of the knee Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 June (revised 2002 May); 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3355&nbr=2581&a mp;string=degenerative+AND+joint+AND+disease 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 degenerative joint disease. 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.

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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

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to degenerative joint disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with degenerative joint disease. 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 degenerative joint disease. 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 “degenerative joint disease” (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

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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 your search to “Organizations” and “degenerative joint disease”. 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 “degenerative joint disease” (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 “degenerative joint disease” (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.21

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

21

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)22: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

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/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

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/

•

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/

•

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

•

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

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

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/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

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

•

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

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

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/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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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

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

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

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

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/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

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

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

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

•

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

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

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

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

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/

•

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).

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

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

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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DEGENERATIVE JOINT DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Aberrant: Wandering or deviating from the usual or normal course. [EU] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Accommodation: Adjustment, especially that of the eye for various distances. [EU] 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] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acrylamide: A colorless, odorless, highly water soluble vinyl monomer formed from the hydration of acrylonitrile. It is primarily used in research laboratories for electrophoresis, chromatography, and electron microscopy and in the sewage and wastewater treatment industries. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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] 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] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH]

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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] 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] 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] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] 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] 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] 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] 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] 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] Ankle: That part of the lower limb directly above the foot. [NIH] Anomalies: Birth defects; abnormalities. [NIH]

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Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [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] 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] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Arthrosis: A disease of a joint. [EU] Articular: Of or pertaining to a joint. [EU]

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Articulation: The relationship of two bodies by means of a moveable joint. [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] Astigmatism: A condition in which the surface of the cornea is not spherical; causes a blurred image to be received at the retina. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Avian: A plasmodial infection in birds. [NIH] 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] 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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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] Biomechanic: The science of the application of mechanics to living creatures. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] 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] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] Body Fluids: Liquid components of living organisms. [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] 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] 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] Bruxism: A disorder characterized by grinding and clenching of the teeth. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] 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] 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 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] 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] 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]

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Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] 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] 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] 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] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [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 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 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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph 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

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relatively fixed personality traits and habitual modes of response of an individual. [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] 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] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) 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] 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] 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] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [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 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] 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 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]

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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] 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] 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] 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]

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Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computerized axial 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 CAT scan, computed tomography (CT scan), or computerized tomography. [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] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [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] 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] Constriction: The act of constricting. [NIH] 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] 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] Convalescence: The period of recovery following an illness. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cutaneous: Having to do with the skin. [NIH]

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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] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [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 (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] 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] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] 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] Diagnostic procedure: A method used to identify a disease. [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] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] 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] 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] 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]

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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 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] Duodenum: The first part of the small intestine. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [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] Elastin: The protein that gives flexibility to tissues. [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]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] 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] Epiphyseal: Pertaining to or of the nature of an epiphysis. [EU] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

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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] Etodolac: A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and in the alleviation of postoperative pain. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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 Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] 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 Manifestations: Ocular disorders attendant upon non-ocular disease or injury. [NIH] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [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] 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] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] 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] Flow Cytometry: Technique using an instrument system for making, processing, and

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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] 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 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] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fossa: A cavity, depression, or pit. [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] Gait: Manner or style of walking. [NIH] Gamma irradiation: A type of radiation therapy that uses gamma radiation. Gamma radiation is a type of high-energy radiation that is different from x-rays. [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] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [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]

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Genotype: The genetic constitution of the individual; the characterization of the genes. [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] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [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] 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] 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] 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] Grafting: The operation of transfer of tissue from one site to another. [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] 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] 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] Handedness: Preference for using right or left hand. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemosiderin: Molecule which can bind large numbers of iron atoms. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH]

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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydration: Combining with water. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] 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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [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] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [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] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens).

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[NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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] 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] 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]

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] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] 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] 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 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]

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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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intestinal: Having to do with the intestines. [NIH] 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] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] 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] 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] 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] 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] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [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] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [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] Lesion: An area of abnormal tissue change. [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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and

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strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] 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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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]

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 different populations of cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] 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] 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

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computerized images. The concept includes proton spin tomographic techniques. [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] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meniscus: A fibro-cartilage within a joint, especially of the knee. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [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] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [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] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH]

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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] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [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] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] 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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Morphological: Relating to the configuration or the structure of live organs. [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] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucopolysaccharidoses: Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the

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eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] 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] Nearsightedness: The common term for myopia. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [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] 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] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] 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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [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

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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] Opacity: Degree of density (area most dense taken for reading). [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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 surgeon: A dentist with special training in surgery of the mouth and jaw. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] 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 from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Patella: The flat, triangular bone situated at the anterior part of the knee. [NIH] 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 Education: The teaching or training of patients concerning their own health needs. [NIH]

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Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [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] 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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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 phenotype, characteristic of yeasts. [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] 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] 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]

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]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [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 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] 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]

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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] 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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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] Postoperative: After surgery. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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]

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Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] 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] 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] 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] 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] 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] 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] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [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] 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] 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]

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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] 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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [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]

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, 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] Radioactive: Giving off radiation. [NIH] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [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] 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] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive

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error (myopia, hyperopia, or astigmatism). [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] 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] 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] 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 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] 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] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [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] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of

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the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue 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] 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] 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] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Rotator: A muscle by which a part can be turned circularly. [NIH] Rotator Cuff: The musculotendinous sheath formed by the supraspinatus, infraspinatus, subscapularis, and teres minor muscles. These help stabilize the head of the humerus in the glenoid fossa and allow for rotation of the shoulder joint about its longitudinal axis. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [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] 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] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [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

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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] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [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] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Tagged Sites: Short, tagged tracts of DNA sequence that are used as landmarks in genome mapping. In most instances, 200 to 500 base pairs of sequence define a Sequence Tagged Site (STS) that is operationally unique in the human genome (i.e., can be specifically detected by the polymerase chain reaction in the presence of all other genomic sequences). The overwhelming advantage of STSs over mapping landmarks defined in other ways is that the means of testing for the presence of a particular STS can be completely described as information in a database. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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]

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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [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] 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] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH]

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Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a 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] 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] 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] Spondylitis: Inflammation of the vertebrae. [EU] Stabilization: The creation of a stable state. [EU] Standardize: To compare with or conform to a standard; to establish standards. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] 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] 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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [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] Substrate: A substance upon which an enzyme acts. [EU] 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]

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Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synchrotron: An accelerator in which the particles are guided by an increasing magnetic field while they are accelerated several times in an approximately circular path by electric fields produced by a high-frequency generator. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] 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 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] Talus: The second largest of the tarsal bones and occupies the middle and upper part of the tarsus. [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] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [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] 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] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] 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] Tomography: Imaging methods that result in sharp images of objects located on a chosen

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plane and blurred images located above or below the plane. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] 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] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] 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] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [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] Tubercle: A rounded elevation on a bone or other structure. [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] 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] 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] 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] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH]

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Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [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] 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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [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]

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INDEX A Aberrant, 6, 81 Abrasion, 54, 81 Accommodation, 81, 101 Acetylcholine, 81, 101 Acetylglucosamine, 48, 49, 81 Acrylamide, 48, 81 Acrylonitrile, 81 Adrenal Cortex, 81, 89, 95, 105 Adverse Effect, 66, 68, 81, 109 Aerobic, 4, 81 Aerobic Exercise, 4, 81 Affinity, 81, 99, 109 Ageing, 9, 81 Albumin, 82, 111 Algorithms, 7, 10, 82, 84 Alimentary, 82, 102 Alkaline, 82, 85 Alternative medicine, 82 Ameliorated, 16, 82 Amino acid, 82, 83, 95, 99, 103, 104, 105, 108, 112 Amino Acid Sequence, 82, 83 Anaesthesia, 82, 96 Analgesic, 18, 82, 90, 92, 95, 101, 111 Analog, 5, 82 Anatomical, 82, 87, 96 Androgens, 81, 82, 89 Animal model, 7, 9, 13, 14, 18, 82 Ankle, 33, 64, 82 Anomalies, 3, 82 Anterior Cruciate Ligament, 33, 83 Antiallergic, 83, 89 Antibiotic, 67, 83, 102, 110 Antibodies, 13, 83, 96, 98, 104 Antibody, 15, 81, 83, 88, 95, 96, 97, 100, 106 Antigen, 81, 83, 88, 95, 96 Anti-inflammatory, 18, 28, 47, 49, 69, 83, 84, 89, 90, 92, 94, 95, 96, 101, 103, 108, 111 Anti-Inflammatory Agents, 83, 84, 89 Antimicrobial, 83, 90 Antineoplastic, 83, 89 Antipyretic, 83, 90, 101, 111 Aphakia, 83, 107 Apoptosis, 36, 83, 86, 90 Arginine, 83, 101

Arteries, 83, 85, 89, 99 Arthroplasty, 9, 11, 19, 21, 24, 29, 33, 83 Arthroscopy, 24, 33, 64, 83 Arthrosis, 49, 83 Articular, 5, 6, 8, 9, 12, 13, 14, 15, 16, 36, 46, 48, 50, 54, 83, 97, 102 Articulation, 84, 99 Aspirin, 19, 25, 84 Astigmatism, 84, 107 Asymptomatic, 20, 84 Atypical, 20, 84 Avian, 36, 84 B Basement Membrane, 84, 92 Bilateral, 20, 84 Bile, 84, 98, 110 Biochemical, 9, 13, 19, 46, 50, 84, 93, 102 Bioengineering, 4, 10, 13, 58, 84 Biological therapy, 84, 94 Biological Transport, 84, 90 Biomarkers, 67, 84 Biomechanic, 26, 84 Biosynthesis, 16, 84 Biotechnology, 17, 59, 84 Bivalent, 84, 99 Blood Coagulation, 84, 85 Blood pressure, 85, 100, 109 Blood vessel, 85, 86, 87, 91, 97, 98, 99, 103, 109, 112 Body Fluids, 46, 50, 84, 85, 109, 112 Bone Marrow, 5, 67, 85, 93, 98, 100 Bowel, 85, 97 Bradykinin, 85, 101 Bruxism, 69, 85 Buccal, 48, 85, 98 Bursitis, 47, 85 C Calcium, 12, 85, 88, 92, 95 Calcium Pyrophosphate, 12, 85 Calculi, 85, 94 Capsules, 85, 91 Carbohydrate, 85, 89, 104, 109 Carcinogenic, 85, 110 Carcinoma, 13, 85 Cardiac, 85, 100, 110 Cardiorespiratory, 81, 86 Cardiovascular, 4, 86 Carotene, 86, 107

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Case report, 86, 87 Case series, 86, 87 Caspase, 16, 86 Cataract, 83, 86, 107 Caudal, 86, 104 Causality, 9, 86 Cell, 5, 9, 16, 83, 84, 86, 87, 88, 90, 91, 92, 93, 94, 96, 97, 100, 101, 103, 104, 106, 107, 113 Cell Death, 83, 86, 101 Cell Differentiation, 5, 86 Cell Division, 86, 94, 100, 103 Cell Size, 86, 93 Cell Survival, 86, 94 Cervical, 17, 26, 86 Cervix, 86 Character, 86 Chin, 4, 87, 99 Cholesterol, 84, 87, 110 Chondrocytes, 5, 14, 36, 87, 92 Chondroitin sulfate, 36, 37, 39, 50, 87 Choroid, 87, 107 Chromatin, 83, 87 Chromosome, 11, 87, 98 Chronic, 11, 16, 20, 26, 32, 47, 87, 96, 110, 111 CIS, 87, 107 Cleft Palate, 3, 87 Clinical study, 23, 87 Clinical trial, 4, 9, 19, 54, 59, 87, 89, 90, 100, 106 Clone, 12, 87 Cloning, 84, 87 Collagen, 7, 9, 14, 82, 84, 87, 95, 104, 105 Collagen disease, 87, 95 Colon, 88, 97 Comorbidity, 32, 88 Complement, 88 Complementary and alternative medicine, 39, 41, 88 Complementary medicine, 39, 88 Computational Biology, 59, 88 Computed tomography, 14, 26, 88, 89 Computer Simulation, 6, 89 Computerized axial tomography, 88, 89 Computerized tomography, 88, 89 Cones, 89, 107 Connective Tissue, 3, 46, 49, 50, 85, 87, 89, 98, 99, 105, 108, 111 Connective Tissue Cells, 89 Constriction, 89, 97 Contraindications, ii, 89

Control group, 4, 89 Convalescence, 9, 89 Cornea, 84, 89, 94 Coronary, 89, 99 Coronary Thrombosis, 89, 99 Corticosteroid, 48, 89, 105, 110 Cranial, 89, 94, 101, 102, 112 Cutaneous, 24, 89, 98 Cyclic, 16, 90, 94, 101 Cysteinyl, 90, 99 Cytokine, 14, 90 Cytoplasm, 83, 90, 99, 100, 108 D Decompression, 29, 90 Decompression Sickness, 90 Deletion, 83, 90 Density, 7, 90, 93, 102, 104 Detergents, 8, 90 Diagnostic procedure, 13, 32, 45, 90 Diclofenac, 24, 90 Diclofenac Sodium, 90 Diffusion, 7, 84, 90 Digestion, 82, 84, 85, 90, 97, 98, 110 Direct, iii, 8, 11, 90, 106 Discrete, 5, 90, 111 Distal, 10, 90, 97 Dorsal, 90, 104 Double-blind, 18, 24, 25, 26, 27, 30, 90 Drive, ii, vi, 10, 35, 69, 91 Drug Tolerance, 91, 111 Duodenum, 84, 91, 110 Dysmenorrhea, 91, 101, 103 Dysplasia, 4, 11, 34, 91 E Efficacy, 9, 25, 28, 30, 91 Effusion, 91, 111 Elastin, 87, 91 Electrolyte, 89, 91, 100, 109 Electrophoresis, 81, 91 Embryo, 86, 91, 96 Endogenous, 14, 91 Endothelial cell, 91, 92 Endothelium, 91, 101 Endothelium-derived, 91, 101 Enteric-coated, 19, 91 Environmental Health, 58, 60, 91 Enzymatic, 12, 82, 85, 86, 88, 91, 104, 107 Enzyme, 14, 86, 90, 91, 93, 94, 96, 99, 100, 104, 106, 110, 113 Epiphyseal, 3, 7, 91 Epithelium, 84, 91, 107 Erythrocytes, 85, 91

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Esophagus, 91, 110 Etidronate, 18, 92 Etodolac, 24, 25, 30, 92 Evoke, 92, 110 Excitation, 92, 93 Exogenous, 91, 92 Extracellular, 5, 9, 12, 14, 16, 46, 50, 89, 92, 109 Extracellular Matrix, 5, 9, 14, 16, 46, 50, 89, 92 Extracellular Space, 92 Extraction, 83, 92, 107 Extremity, 5, 92 Eye Manifestations, 3, 92 F Facial, 3, 31, 32, 92 Facial Pain, 32, 92 Family Planning, 59, 92 Fat, 85, 86, 89, 92, 108, 109, 111 Femoral, 7, 92 Femur, 10, 83, 92, 111 Fibroblast Growth Factor, 25, 92 Fibula, 92, 111 Filtration, 46, 49, 92 Fissure, 87, 92 Flow Cytometry, 5, 92 Fluorescence, 93 Fluorescent Dyes, 93 Foramen, 87, 93 Fossa, 93, 108 Friction, 8, 93, 98 G Gait, 5, 93 Gamma irradiation, 11, 93 Gas, 90, 93, 95, 101, 110 Gastric, 34, 47, 93 Gastrointestinal, 47, 67, 85, 93, 103, 112 Gastrointestinal tract, 47, 93, 112 Gene, 6, 11, 12, 15, 16, 84, 93 Gene Expression, 15, 16, 93 Gene Therapy, 6, 93 Generator, 93, 111 Genetic Counseling, 11, 93 Genotype, 36, 94, 103 Gland, 81, 94, 98, 102, 103, 105, 109, 110 Glossopharyngeal Nerve, 92, 94 Glucocorticoid, 94, 95, 105 Glycoprotein, 8, 94 Glycosaminoglycan, 7, 87, 94 Gonadal, 94, 110 Gout, 31, 94, 101 Governing Board, 94, 104

Graft, 9, 94 Grafting, 94, 96 Growth factors, 5, 16, 94 Guanylate Cyclase, 94, 101 H Half-Life, 94, 103 Handedness, 43, 94 Health Status, 5, 28, 32, 94 Hemoglobinopathies, 93, 94 Hemophilia, 29, 30, 94 Hemosiderin, 25, 94 Hereditary, 94 Heredity, 93, 95 Homologous, 84, 93, 95 Hormonal, 89, 95 Hormone, 89, 95, 105, 108 Hybrid, 6, 87, 95 Hydration, 81, 95 Hydrocortisone, 48, 95 Hydrogen, 85, 95, 100 Hydrolysis, 12, 95, 104, 106 Hydrophobic, 90, 95 Hydroxylysine, 87, 95 Hydroxyproline, 82, 87, 95 Hypercalcemia, 92, 95 Hyperopia, 95, 107 Hyperplasia, 17, 26, 95 Hypersensitivity, 95, 108 Hypertrophy, 95 Hyperuricemia, 94, 95 Hypoplasia, 3, 95 I Ibuprofen, 18, 95 Idiopathic, 19, 26, 95 Immune response, 83, 89, 95 Immune system, 84, 95, 96, 98, 113 Immunoglobulin, 83, 96, 100 Immunohistochemistry, 5, 96 Impairment, 48, 96 Implantation, 11, 96 In situ, 10, 15, 96 In vitro, 8, 14, 16, 93, 96, 104 In vivo, 6, 9, 16, 93, 96 Incision, 96, 97 Indomethacin, 25, 47, 49, 96, 111 Induction, 14, 82, 96 Infarction, 89, 96, 99 Infection, 15, 46, 84, 96, 98, 108, 110, 113 Inflammation, 4, 7, 15, 47, 50, 82, 83, 84, 85, 95, 96, 104, 108, 110, 111 Innervation, 28, 96 Inorganic, 85, 96

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Insight, 11, 96 Interleukin-1, 14, 96 Interleukin-2, 96, 97 Intermittent, 14, 97 Intestinal, 47, 86, 97 Intestine, 47, 85, 91, 95, 97 Intracellular, 14, 96, 97, 98, 101 Intramuscular, 97, 102 Intravenous, 97, 102 Invasive, 6, 7, 97, 98 Involuntary, 97, 100, 106 Irradiation, 97 Ischemia, 7, 97 J Joint Capsule, 97, 111 Joint Instability, 10, 16, 97 K Kb, 58, 97 Kidney Cortex, 97, 99 L Large Intestine, 97 Lavage, 50, 51, 97 Lens, 83, 86, 97, 113 Lesion, 97, 98, 112 Leukemia, 93, 97 Leukocytes, 85, 96, 97, 100 Ligament, 10, 83, 97, 105 Ligands, 13, 98 Linkage, 11, 16, 98 Liver, 82, 84, 98, 99 Localization, 5, 26, 96, 98 Localized, 96, 98, 103, 112 Lubricants, 98 Lubrication, 8, 49, 98 Lumbar, 22, 28, 98 Lupus, 98, 111 Lymph, 86, 91, 98 Lymph node, 86, 98 Lymphatic, 46, 50, 91, 96, 98, 99, 110, 111 Lymphatic system, 46, 50, 98, 110, 111 Lymphocyte, 31, 83, 98 Lymphocyte Subsets, 31, 98 Lymphoid, 83, 98 Lysosomal Storage Diseases, 98, 100 M Macrophage, 96, 98 Magnetic Resonance Imaging, 5, 98 Mammary, 13, 99 Mandible, 87, 99 Mastication, 99, 112 Masticatory, 53, 99 Medial, 10, 25, 99, 111

MEDLINE, 59, 99 Membrane, 31, 81, 87, 88, 99, 107, 111, 113 Meniscus, 10, 13, 25, 33, 99 Menopause, 99, 104 Mental, iv, 4, 58, 60, 87, 99, 106 Mental Health, iv, 4, 58, 60, 99, 106 Mercury, 93, 99 Mesenchymal, 5, 99 Metabolic disorder, 4, 94, 99 Metallothionein, 26, 99 Metastasis, 46, 49, 50, 99 Metastatic, 34, 99, 108 Metatarsophalangeal Joint, 19, 99 MI, 79, 99 Microbiology, 84, 99 Microorganism, 99, 113 Migration, 46, 50, 99 Mineralocorticoids, 81, 89, 100 Mitochondrial Swelling, 100, 101 Mitosis, 83, 100 Modeling, 6, 10, 100 Molecular, 8, 9, 10, 11, 12, 13, 15, 34, 48, 59, 61, 84, 88, 99, 100, 112 Molecular mass, 12, 100 Molecule, 46, 50, 83, 87, 88, 91, 92, 94, 95, 100, 105, 106 Monitor, 7, 46, 50, 100, 101 Monoclonal, 15, 97, 100, 106 Monocytes, 96, 97, 100 Morphological, 14, 81, 91, 100 Morphology, 20, 86, 100 Motility, 96, 100 Mucins, 100, 108 Mucopolysaccharidoses, 36, 100 Multicenter study, 25, 27, 30, 100 Myocardium, 99, 100 Myopia, 3, 100, 101, 107 N Naproxen, 27, 67, 101 Nearsightedness, 101 Necrosis, 7, 83, 96, 99, 101 Neoplastic, 92, 95, 101 Nerve, 87, 94, 96, 101, 102, 108, 110, 112 Nervous System, 81, 101, 102 Networks, 15, 101 Neural, 69, 101, 107 Neural Pathways, 69, 101 Neuralgia, 32, 101 Neuromuscular, 51, 81, 101 Nitric Oxide, 36, 101 Nitrogen, 82, 90, 100, 101, 112 Nuclear, 101

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Nuclei, 93, 98, 100, 101, 102 Nucleus, 83, 87, 90, 100, 101 O Ocular, 92, 101 Odds Ratio, 101, 107 Opacity, 86, 90, 102 Opsin, 102, 107, 108 Optic Nerve, 102, 107 Oral surgeon, 3, 102 Orofacial, 92, 102 Orthopaedic, 9, 11, 25, 65, 102 Osteonecrosis, 29, 102 Oxazolidinones, 47, 102 P Palate, 4, 87, 94, 102 Pancreas, 84, 102, 112 Parenteral, 50, 102 Partial remission, 102, 107 Patella, 28, 102 Pathogenesis, 5, 8, 15, 28, 53, 102 Pathologic, 28, 83, 89, 95, 102 Pathologic Processes, 83, 102 Pathologies, 14, 102 Pathophysiology, 32, 102 Patient Education, 68, 74, 76, 79, 102 Pedigree, 11, 103 Pelvis, 98, 103, 112 Peptide, 46, 49, 82, 92, 103, 104, 105, 106 Perforation, 47, 93, 103 Perfusion, 7, 103 Phantom, 7, 103 Pharmacologic, 94, 103, 112 Phenotype, 11, 16, 103 Phosphorus, 85, 103 Phosphorylation, 17, 103 Physical Therapy, 69, 103 Physiologic, 84, 94, 103, 106 Pigment, 103, 107 Pigmentation, 30, 103 Pilot study, 26, 103 Piroxicam, 28, 30, 34, 103 Pituitary Gland, 89, 92, 103 Plants, 100, 103, 108, 112 Plasma, 24, 82, 83, 100, 104 Plasma cells, 83, 104 Platelet Aggregation, 101, 104 Platelets, 101, 104 Pneumonia, 89, 104 Polyethylene, 10, 104 Polymerase, 104, 109 Polymerase Chain Reaction, 104, 109 Polymers, 48, 104, 105

Polymorphic, 11, 87, 104 Polypeptide, 82, 87, 104 Polysaccharide, 83, 94, 104, 105 Posterior, 10, 16, 54, 87, 90, 94, 102, 104 Postmenopausal, 26, 104 Postoperative, 92, 103, 104 Potentiates, 96, 104 Practice Guidelines, 60, 69, 104 Precipitating Factors, 86, 105 Precursor, 91, 105, 112 Prednisolone, 48, 105 Prevalence, 53, 102, 105 Progesterone, 105, 110 Prognostic factor, 5, 105 Progression, 6, 10, 13, 14, 82, 105 Progressive, 9, 13, 16, 51, 86, 91, 100, 101, 102, 105 Proline, 87, 95, 105 Prostaglandins, 96, 105 Prostaglandins A, 96, 105 Prostate, 84, 105, 112 Prosthesis, 97, 105 Protein S, 84, 105, 108 Proteins, 13, 27, 31, 46, 82, 83, 86, 87, 88, 90, 94, 96, 100, 101, 103, 104, 105, 106, 109 Proteoglycan, 14, 16, 36, 105 Proteolytic, 12, 13, 88, 106 Public Health, 4, 60, 106 Public Policy, 59, 106 Publishing, 17, 36, 106 Pulse, 100, 106 R Race, 99, 106 Radiation, 93, 97, 103, 106, 113 Radiation therapy, 93, 97, 106 Radioactive, 94, 95, 96, 97, 101, 106 Radiography, 7, 13, 64, 106 Radiolabeled, 15, 97, 106 Randomized, 4, 26, 91, 106 Receptor, 16, 83, 106 Recombinant, 15, 106 Recombination, 93, 106 Recurrence, 46, 49, 106 Refer, 1, 85, 88, 98, 106, 112 Reflex, 69, 106 Refraction, 13, 100, 106, 110 Refractive Power, 100, 107 Regeneration, 9, 92, 107 Regimen, 91, 107 Relative risk, 9, 107 Reliability, 17, 26, 107

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Remission, 46, 106, 107 Respiration, 100, 107 Retina, 25, 84, 87, 89, 97, 100, 102, 107, 108, 113 Retinal, 3, 102, 107, 108 Retinal Detachment, 3, 107 Retinol, 107, 108 Retroviral vector, 93, 107 Rheology, 8, 107 Rheumatism, 20, 22, 27, 28, 31, 95, 108 Rheumatoid, 8, 19, 25, 29, 30, 31, 47, 64, 87, 92, 101, 103, 108 Rheumatoid arthritis, 8, 19, 25, 29, 30, 31, 47, 87, 92, 101, 103, 108 Rheumatology, 14, 26, 28, 31, 66, 67, 68, 108 Rhodopsin, 102, 107, 108 Ribosome, 108, 112 Risk factor, 9, 16, 86, 107, 108 Rods, 107, 108 Rotator, 21, 108 Rotator Cuff, 21, 108 Rural Population, 21, 108 S Salicylate, 19, 108 Saliva, 8, 108 Salivary, 108 Salivary glands, 108 Saponins, 108, 110 Scatter, 13, 103, 108 Scoliosis, 26, 108 Screening, 67, 87, 108 Secondary tumor, 99, 108 Secretion, 89, 100, 109 Segmentation, 7, 109 Self Care, 54, 109 Sequence Analysis, 11, 109 Sequence Tagged Sites, 11, 109 Sequencing, 51, 104, 109 Serum, 30, 46, 49, 50, 82, 88, 100, 109 Shock, 95, 109, 112 Side effect, 47, 48, 49, 81, 84, 95, 103, 109, 112 Signs and Symptoms, 68, 107, 109 Skeletal, 20, 24, 28, 43, 82, 109 Skeleton, 92, 109, 111 Skull, 109, 111 Sodium, 27, 37, 90, 94, 100, 101, 109 Soft tissue, 7, 13, 48, 54, 85, 109 Specialist, 70, 109 Species, 95, 99, 100, 106, 110, 112, 113 Spectrum, 100, 110

Sperm, 82, 87, 110 Spinal cord, 87, 101, 106, 110 Spleen, 98, 110 Spondylitis, 47, 92, 110 Stabilization, 10, 110 Standardize, 8, 110 Sterilization, 11, 110 Steroid, 48, 108, 110 Steroid therapy, 48, 110 Stimulant, 16, 110 Stimulus, 16, 91, 92, 96, 106, 110, 111 Stomach, 47, 91, 93, 95, 97, 110 Stress, 6, 10, 14, 16, 108, 110 Subacute, 96, 110 Subclinical, 96, 110 Subcutaneous, 102, 110 Substrate, 15, 110 Suction, 92, 110 Suppression, 89, 111 Symphysis, 87, 105, 111 Symptomatic, 20, 28, 31, 47, 111 Synchrotron, 13, 111 Synovial, 8, 13, 20, 24, 25, 26, 31, 48, 50, 51, 97, 111 Synovial Fluid, 8, 13, 20, 24, 48, 51, 111 Synovial Membrane, 50, 97, 111 Synovitis, 26, 29, 50, 111 Systemic, 31, 50, 85, 87, 96, 97, 105, 106, 111 Systemic lupus erythematosus, 31, 87, 111 T Talus, 111 Temporal, 8, 111 Tendon, 85, 111 Thigh, 92, 111 Thorax, 98, 111 Threshold, 9, 111 Thymus, 98, 111 Tibia, 10, 83, 92, 111 Tolerance, 34, 111 Tolmetin, 32, 111 Tomography, 7, 111 Toxic, iv, 112 Toxicology, 60, 112 Toxin, 111, 112 Transfection, 84, 93, 112 Translation, 10, 82, 112 Transplantation, 16, 112 Trauma, 20, 48, 51, 69, 101, 112 Trigeminal, 92, 112 Tryptophan, 87, 112 Tubercle, 25, 112

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Tumor marker, 84, 112 U Ulcer, 112 Ulceration, 47, 112 Uric, 94, 95, 112 Urinary, 85, 112, 113 Uterus, 86, 105, 112 V Vaginal, 98, 112 Vascular, 24, 28, 46, 50, 87, 91, 96, 101, 112 Vasodilators, 101, 112 Vertebrae, 34, 110, 112 Vertebral, 20, 112 Veterinary Medicine, 59, 112 Viscosity, 8, 48, 108, 113 Vitreous, 97, 107, 113

Vitreous Body, 107, 113 Vitreous Humor, 107, 113 Vitro, 16, 113 Vivo, 6, 16, 113 W Weight-Bearing, 16, 113 White blood cell, 83, 97, 98, 104, 113 Wound Healing, 92, 113 X Xanthine, 47, 113 Xenograft, 82, 113 X-ray, 7, 13, 22, 64, 69, 88, 89, 93, 97, 101, 106, 113 Y Yeasts, 103, 113

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Degenerative Joint Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References