CORTICOSTEROIDS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©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., 1960Corticosteroids: 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: 0-497-00306-6 1. Corticosteroids-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on corticosteroids. 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 CORTICOSTEROIDS .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Corticosteroids .............................................................................. 7 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND CORTICOSTEROIDS ........................................................................ 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Corticosteroids ........................................................................... 115 Federal Resources on Nutrition ................................................................................................. 119 Additional Web Resources ......................................................................................................... 120 CHAPTER 3. ALTERNATIVE MEDICINE AND CORTICOSTEROIDS .................................................. 123 Overview.................................................................................................................................... 123 National Center for Complementary and Alternative Medicine................................................ 123 Additional Web Resources ......................................................................................................... 130 General References ..................................................................................................................... 141 CHAPTER 4. DISSERTATIONS ON CORTICOSTEROIDS .................................................................... 143 Overview.................................................................................................................................... 143 Dissertations on Corticosteroids ................................................................................................ 143 Keeping Current ........................................................................................................................ 144 CHAPTER 5. PATENTS ON CORTICOSTEROIDS............................................................................... 145 Overview.................................................................................................................................... 145 Patents on Corticosteroids ......................................................................................................... 145 Patent Applications on Corticosteroids...................................................................................... 168 Keeping Current ........................................................................................................................ 182 CHAPTER 6. BOOKS ON CORTICOSTEROIDS .................................................................................. 185 Overview.................................................................................................................................... 185 Book Summaries: Federal Agencies............................................................................................ 185 Book Summaries: Online Booksellers......................................................................................... 187 Chapters on Corticosteroids ....................................................................................................... 188 CHAPTER 7. PERIODICALS AND NEWS ON CORTICOSTEROIDS .................................................... 193 Overview.................................................................................................................................... 193 News Services and Press Releases.............................................................................................. 193 Newsletter Articles .................................................................................................................... 195 Academic Periodicals covering Corticosteroids.......................................................................... 197 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 199 Overview.................................................................................................................................... 199 U.S. Pharmacopeia..................................................................................................................... 199 Commercial Databases ............................................................................................................... 203 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 207 Overview.................................................................................................................................... 207 NIH Guidelines.......................................................................................................................... 207 NIH Databases........................................................................................................................... 209 Other Commercial Databases..................................................................................................... 211 APPENDIX B. PATIENT RESOURCES ............................................................................................... 213 Overview.................................................................................................................................... 213 Patient Guideline Sources.......................................................................................................... 213 Finding Associations.................................................................................................................. 222 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 225 Overview.................................................................................................................................... 225
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Preparation................................................................................................................................. 225 Finding a Local Medical Library................................................................................................ 225 Medical Libraries in the U.S. and Canada ................................................................................. 225 ONLINE GLOSSARIES................................................................................................................ 231 Online Dictionary Directories ................................................................................................... 234 CORTICOSTEROIDS DICTIONARY ....................................................................................... 235 INDEX .............................................................................................................................................. 337
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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 corticosteroids 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 corticosteroids, 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 corticosteroids, 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 corticosteroids. 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 corticosteroids, 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 corticosteroids. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON CORTICOSTEROIDS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on corticosteroids.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and corticosteroids, 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 “corticosteroids” (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: •
Cyclosporin A Is a Promising Alternative to Corticosteroids in Autoimmmune Hepatitis Source: Digestive Diseases and Sciences. 46(6): 1321-1327. June 2001. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail:
[email protected]. Website: www.wkap.nl. Summary: Autoimmune hepatitis (AIH), a chronic T cell mediated liver injury, is treated with corticosteroids, with or without azathioprine. Corticosteroids are not universally effective and have serious side effects. Cyclosporin A was effective in refractory cases (those resistant to first lines of treatment). This article reports on a study undertaken to assess efficacy and safety of cyclosporin A (Neoral) in induction of remission in patients
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with AIH (n = 19). All 19 patients (nine as their first line of treatment) were treated with cyclosporin A in an open label trial and followed for 26 weeks. Liver biopsy was done and hepatitis activity index (HAI) determined at the beginning and end of treatment. Four patients did not complete the study for various reasons. Mean AST and ALT levels (measures of liver function) decreased from 948.77 to 100.6 and from 454.8 to 78.5, respectively. HAI decreased from 15.2 to 7.14. Serum creatinine did not change significantly. The authors conclude that low dose cyclosporin A appears to be safe and effective even in treatment nave autoimmune hepatitis patients. The authors call for randomized controlled trials to further test the use of this drug. 2 figures. 5 tables. 29 references. •
Immunoreactive Propensity of Autoimmune Hepatitis: Is It CorticosteroidDependent After Liver Transplantation? (editorial) Source: Liver Transplantation and Surgery. 5(5): 460-462. September 1999. Contact: Available from W.B. Saunders Company. Liver Transplantation and Surgery, Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Summary: Autoimmune hepatitis implies loss of immune tolerance for the native liver (the person's immune system attacks the liver). This editorial discusses the incidence of this occurrence after the patient has undergone a liver transplantation and the relationship of drug therapy in causing or preventing this occurrence. Recurrence has been associated with reduction in the doses of immunosuppressive medication and control is typically (but not always) reestablished by dose adjustments. Acute and chronic cellular rejection are other manifestations of immunoreactivity after liver transplantation. This editorial comments on a related article in the same issue that contends that many patients (17 of 25 patients in the study, 68 percent) can be withdrawn from the corticosteroid medications without causing a recurrence of autoimmune hepatitis. Removal of the corticosteroid medications was shown to reduce serum cholesterol levels and offer improved management of hypertension and diabetes. The author of this editorial cautions against implementing this strategy of corticosteroid removal for four reasons. First, the results of this recent research study (Trouillot et al) are not consonant with other research studies; second, it is unclear what alternative immunosuppressive measures were undertaken in the patients who were withdrawn from corticosteroids; third, durations of followup after removing the corticosteroids must be extended (to ensure the absence of long term consequences); and fourth, potential risk factors for immunoreactivity (such as age, gender, race, and HLA DR status) were not fully assessed in the Trouillot study. The author concludes that Trouillot et al. have described an important experience and their observations must be extended and corroborated so that immunosuppressive regimens for autoimmune hepatitis after transplantation can be optimized. 29 references.
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Corticosteroids, Cyclophosphamide, and Chlorambucil Therapy of Membranous Nephropathy Source: Seminars in Nephrology. 23(4): 355-361. July 2003. Summary: Corticosteroids and cytotoxic agents have been studied widely in membranous nephropathy (MN). However, controlled studies with corticosteroids have not shown a clear benefit of these agents on the outcome of the disease. This article reviews research studies on treating MN with corticosteroids, cytotoxic drugs, or both. Some controlled trials reported that cytotoxic agents can reduce proteinuria
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significantly, but it was difficult to assess the efficacy of these drugs in protecting renal (kidney) function because of the short follow up period of these studies. Three randomized controlled trials showed that a 6 month treatment regimen based on corticosteroids and a cytotoxic agent, giving each for 1 month at a time in an alternating schedule, could favor remission of the nephrotic syndrome and protect renal function. Taken together, the results of these trials at the end of the follow up period showed 74 percent of the 174 treated patients were without nephrotic syndrome, 4 patients were on chronic dialysis, and 2 patients died. Good results with cytotoxic drugs, often associated with corticosteroids, have also been reported in progressive membranous nephropathy. However, in patients with renal insufficiency, side effects were frequent and severe. Moreover, in most cases, renal function improved but did not return to normal. 2 tables. 28 references. •
Supplemental Corticosteroids for Dental Patients with Adrenal Insufficiency: Reconsideration of the Problem Source: JADA. Journal of the American Dental Association. 132: 1580-1587. November 2001. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Dental patients with primary or secondary adrenal insufficiency (AI) may be at risk of experiencing adrenal crisis during or after invasive dental procedures. Since the mid 1950s, supplemental steroids in rather large doses have been recommended for patients with AI to prevent adrenal crisis. This continuing education article reports on a study undertaken to evaluate the need for supplemental steroids in these patients. In this study, the authors searched the literature from 1966 to 2000 using MEDLINE and textbooks for information that addressed AI and adrenal crisis in dentistry. Reference lists of relevant publications and review articles also were examined for information about the topic. The review identified only four reports of purported adrenal crisis in dentistry. Factors associated with the risk of adrenal crisis included the magnitude of surgery, the use of general anesthetics, the health status and stability of the patient, and the degree of pain control. The limited number of reported cases strongly suggests that adrenal crisis is a rare event in dentistry, especially for patients with secondary AI, and most routine dental procedures can be performed without glucocorticoid supplementation. 2 figures. 1 table. 62 references.
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Levamisole Therapy in Corticosteroid-Dependent Nephrotic Syndrome Source: Pediatric Nephrology. 11(4): 415-417. August 1997. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: This article reports on a study in which the effect of prolonged treatment with levamisole was examined in 43 patients (30 boys, 13 girls) with steroid dependent nephrotic syndrome (SDNS). Levamisole is a drug that modulates phagocytic (cells that surround and digest microorganisms and cellular debris) and lymphocytic (white blood cells that assist in immune function) activity. Nephrotic syndrome is a condition characterized by massive edema (fluid accumulation), heavy proteinuria (protein in the urine), hypoalbuminemia (low levels of protein in the blood), and susceptibility to infections. The mean age at the beginning of treatment was 4.0 years (plus or minus 2 years). Fourteen patients had previously received cyclophosphamide with an ensuring remission of 8.5 months (plus or minus 10 months). Following induction of remission
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with prednisolone, levamisole was administratered at a dose of 2.5 milligrams per kilogram of body weight on alternate days. Prednisolone was tapered to 0.5 milligrams per kilogram of body weight on alternate days. The duration of levamisole therapy ranged from 6 to 31 months; 15 patients received levamisole for more than 18 months and 10 for more than 24 months. Prednisolone was discontinued in 18 patients after a mean duration of 11.7 months, whereas in 21 patients, its dose was reduced to 0.2 to 0.4 milligrams per kilogram of body weight on alternate days. The mean relapse rate prior to levamisole therapy was 3.0 relapses per year, which reduced to 0.9 relapses per year during levamisole treatment. A comparison of the response in 14 patients who had previously received cyclophosphamide with the other 29 patients did not show any significant difference. There were no side effects of levamisole therapy The authors conclude that treatment with levamisole is beneficial and safe in SDNS, with a marked steroid sparing effect. A significant proportion of these patients can be kept in remission on levamisole alone. 3 tables. 16 references. •
Topical Corticosteroids in Association with Miconazole and Chlorhexidine in the Long-Term Management of Atrophic-Erosive Oral Lichen Planus: A PlaceboControlled and Comparative Study Between Source: Oral Diseases. 5(1): 44-49. January 1999. Contact: Available from Stockton Press. Marketing Department, Houndmills, Basingstoke, Hampshire RG21 6XS, United Kingdom. (800) 747-3187. Website: www.stockton-press.co.uk. Summary: This article reports on a study undertaken to evaluate the efficacy of a combination of topical corticosteroids with topical antifungal drugs in the treatment of atrophic-erosive forms of oral lichen planus (OLP). The study population consisted of 60 patients with OLP subdivided into three groups matched for sex and age. The first group (n = 25) received 0.05 percent clobetasol propionate ointment; and the second group (n = 24) received 0.05 percent fluocinonide ointment; both groups also received antifungal treatment consisting of miconazole gel and 0.12 percent chlorhexidine mouthwashes. The third group (n = 11), the placebo group, received only a plain ointment (hydroxyethyl cellulose gel), and antifungal treatment as above. All the treatment regimens were carried out for 6 months; each patient was examined every 2 months and for a further 6 months of follow up after active treatment. All patients treated with clobetasol and 90 percent of the patients treated with fluocinonide witness some improvement, whereas in the placebo group only 20 percent of patients improved. However, when considering complete responses, only clobetasol gave significantly better results than placebo. Clobestasol resolved 75 percent of the lesions whereas fluocinonide was effective in 25 percent of cases and placebo in none. Similar results were obtained for symptoms. None of the treated patients contracted oropharyngeal candidiasis. After 6 months of follow up, 65 percent of the clobetasol treated group and 55 percent of the fluocinonide group were stable. Estimation of plasma cortisol levels showed no significant systemic adverse effects of clobetasol or fluocinonide. The authors conclude that a very potent topical corticosteroid such as clobetasol may control OLP in most cases, with no significant adrenal suppression or adverse effects. Moreover, a concomitant antifungal treatment with miconazole gel and chlorhexidine mouthwashes is a useful and safe prophylaxis agent against oropharyngeal candidiasis. 2 figures. 3 tables. 33 references.
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Review Article: Osteoporosis, Corticosteroids and Inflammatory Bowel Disease Source: Alimentary Pharmacology and Therapeutics. 9(3): 237-250. June 1995.
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Contact: Available from Mercury Airfreight International, Ltd. 2323 EF, Randolph Avenue, Avenel, NJ 07001. Summary: This review article summarizes current knowledge about the clinical and pathophysiological aspects of osteoporosis. The author reviews the prevalence, pathogenesis, and treatment of osteoporosis associated with inflammatory bowel disease (IBD). The pathogenesis of osteoporosis associated with IBD is theorized to be multifactorial, with corticosteroid therapy, calcium and vitamin D deficiency, hypogonadism, and malnutrition all potential contributory factors. The author stresses that bone density measurements to predict fracture risk and to define thresholds for prevention and treatment should be performed routinely in patients with inflammatory disease. Hormone replacement therapy is effective in prevention of bone loss in peri-and postmenopausal patients, but the treatment of younger women and men of all ages requires further study. 9 figures. 5 tables. 115 references. (AA-M).
Federally Funded Research on Corticosteroids The U.S. Government supports a variety of research studies relating to corticosteroids. 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 corticosteroids. 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 corticosteroids. The following is typical of the type of information found when searching the CRISP database for corticosteroids: •
Project Title: ACCELERATED PREVALENCE/FACTORS
ATHEROSCLEROSIS
IN
SLE--
Principal Investigator & Institution: Roman, Mary J.; Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Autopsy and observational data suggest that systemic lupus erythematosus (SLE) is associated with premature atherosclerosis and myocardial infarction; however, clinical studies have reported widely varying event rates, and the prevalence of underlying disease (atherosclerosis and myocardial disease) in SLE patient samples and its relation to that in a control population are unknown. The prevailing hypothesis has been that accelerated atherosclerosis is attributable to an increased frequency of conventional risk factors in SLE patients such as hypertension, hyperlipidemia and obesity, all of which may be provoked or potentiated by therapeutic use of corticosteroids. Alternatively, anti2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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phospholipid antibody (APLA), present in about 20% of the SLE patients, may result in vascular occlusions due to abnormal clotting rather than atherosclerosis; however, data are accumulating that suggest that the inflammatory process per se may be important in the initiation and progression of atherosclerosis. Pilot data for this study indicate that underlying non-invasively- detected atherosclerosis is several-fold more common in patients with SLE in comparison to matched control subjects. Furthermore, left ventricular mass, a marker for and mediator of enhanced cardiovascular morbidity and mortality, is strikingly higher in SLE patients, even after adjustment for differences in body size. Neither of these observations is explained by standard risk factors. Thus, the goals of this project are to: 1) establish the prevalence of atherosclerosis and myocardial disease in an unselected population of SLE patients; 2) compare findings to those in a control population; 3) determine whether the excess prevalence of pre-clinical cardiovascular disease is independent of known cardiovascular risk factors and is additionally related to markers of inflammation and immune system activation; and 4) determine whether atherosclerosis and LV hypertrophy progress more rapidly in SLE patients than in control subjects. Based on preliminary data, the investigators hypothesize that pre-clinical disease will be more common in SLE and will not be fully explained by conventional risk factors for atherosclerosis or thrombosis. They further hypothesize that basic aspects of the inflammatory process (to be partially investigated using soluble markers in the current project) are primarily responsible for non-valvular cardiovascular disease in SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACTIVATION OF ENOS BY STEROID HORMONES Principal Investigator & Institution: Liao, James K.; Associate Professor/Director; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 16-MAY-2002; Project End 31-MAR-2007 Summary: (Provided by applicant): Corticosteroids are potent anti-inflammatory agents, which are used in the treatment of asthma, hypersensitivity reactions, and autoimmune diseases. Corticosteroids inhibit the inflammatory response through binding to the glucocorticoid receptor (GR). The GR is a steroid hormone nuclear receptor which when bound to corticosteroids, modulates the expression of target genes by binding to DNA sequences containing glucocorticoid response element (GRE). Although most studies have focused on the GRE-mediated effects of corticosteroids, there is considerable controversy regarding the nuclear actions of OR, particularly in mediating some of the more rapid anti-inflammatory effects of corticosteroids. In cardiovascular disease, corticosteroids exert both beneficial and detrimental effects. Corticosteroids protect the myocardium from ischemic injury, presumably through an anti-inflammatory mechanism. However, corticosteroid therapy can also lead to cardiac rupture, which has precluded their use in acute myocardial infarction. This detrimental effect of corticosteroids has been attributed to its GRE-mediated inhibitory effects on wound healing and cardiac remodeling. Therefore, defining the potential role of nonnuclear OR in cardiovascular diseases could have important therapeutic implications; especially in the development of selective OR modulators which can distinguish between the nuclear and non-nuclear effects of OR. In our pilot studies, we have found that activation of endothelial nitric oxide synthase (eNOS) by corticosteroids is mediated via the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt pathway. Based upon these results, we propose to determine how GR activates P13K; whether GR interacts directly with P13K in a ligand-dependent manner; whether this occurs by nontranscriptional or non-GRE-mediated mechanism; and whether this interaction can be
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generalized to other members of the steroid hormone family of nuclear receptors. Once the interaction site(s) on OR is pinpointed, the physiological significance of this pathway will be tested in mutated OR "knock-in" mice. The significance of these proposed studies is that by linking the OR to P13K, a potential critical step in the non-nuclear action of corticosteroids is suggested and the role of OR is considerably broadened since PI3KIAkt and NO are known to mediate diverse cellular functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACTIVITY DEPENDENT PLASTICITY IN THE AGING BRAIN Principal Investigator & Institution: Cotman, Carl W.; Professor; Inst for Brain Aging/Dementia; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-MAR-2005 Summary: Adapted from applicant's abstract): Exercise has been associated with enhanced cognitive function as well as maintenance of cognitive health. The molecular mechanisms that may underlie this improved brain functioning, however, are only beginning to be identified. Brain-derived neurotrophic factor (BDNF) has been demonstrated to enhance the survival of cortical neurons, promote their recovery after damage, and participate in use-dependent plasticity mechanisms such as long-term potentiation and learning. Thus, BDNF regulation is critical to brain functions. We have demonstrated that exercise (voluntary running) can increase the expression of multiple BDNF transcript forms in rat brain. This effect is rapid (occurring within hours of exercise onset) and is sustained. This effect is regionally selective and is particularly prominent in the hippocampus, a brain region not normally associated with motor activity. A large literature suggests that such trophic factor responses are regulated by many other variables, including specific neurotransmitter and hormone interactions. Recently, a cAMP-response element (CRE) has been identified on the exon III BDNF promoter. The CRE is active in constructs, which suggests the hypothesis that CREbinding protein (CREB) and the regulation of CREB activity may serve as a convergence point for the regulation of induction of the exon Ill-containing BDNF transcript (exon IIIBDNF). Various neurotransmitters, activation of voltage sensitive calcium channels and the hormone estrogen may converge on the regulation of CREB activity and thereby on exon 111BDNF mRNA expression. Exon l-BDNF expression may be regulated by neurotransmitters, estrogen and corticosteroids. Specific studies will be directed toward exploring the role of the NMDA receptor, cholinergic and moluminergic "stems on BDNF expression, because initial evidence suggests that they can modulate BDNF -ion. F," cholinergic and monaminergic systems also appear to modulate cognitive function and behaviaral state. In addition to studies on mechanism, parallel studies will be conducted on the age-dependency, regional specificity, and means to enhance BDNF expression by combined behavioral and pharmacological interventions. Data from the proposed experiments will provide an initial characterization of how a simple, widely practiced activity-exercise-regulates expression of BDNF, a molecule increasingly recognized for its critical role in brain function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACUTE CORTICOSTERIOD ACTIONS IN THE HYPOTHALAMUS Principal Investigator & Institution: Tasker, Jeffrey G.; Professor; Cellular and Molecular Biology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007
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Summary: (provided by applicant): Stress is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis and increased levels of circulating adrenal corticosteroids. Glucocorticoids feed back onto the hypothalamus to inhibit not only corticotropin releasing hormone (CRH) secretion and HPA activation, but also many other hypothalamic neuroendocrine systems. The negative feedback regulation by glucocorticoids occurs in two stages: an acute inhibition of the release of CRH, and a slower down-regulation of CRH and vasopressin synthesis in neurons of the hypothalamic paraventricular nucleus (PVN). To date, it is not known where in the brain glucocorticoids exert their negative feedback regulation of hypothalamic neurosecretion, and what the cellular mechanisms of this feedback are. These questions have profound significance for the treatment of widespread affective disorders, including stress, depression, and eating disorders, that impact large numbers of people. The overall purpose of this proposal is to determine whether acute negative glucocorticoid regulation of PVN neuroendocrine systems occurs directly at the hormone-secreting neurons in the PVN, and to characterize the cellular mechanisms of this regulation. We have preliminary evidence for rapid inhibitory glucocorticoid effects in the PVN mediated by membrane receptor activation and the release of a retrograde endocannabinoid messenger that suppresses excitatory and facilitates inhibitory inputs to PVN neurons. Based on these findings, we propose to conduct whole-cell patchclamp recordings in acute rat hypothalamic slices to test the following specific hypotheses: 1. glucocorticoids inhibit PVN neurons directly by stimulating an endocannabinoid-mediated suppression of glutamate release and facilitation of GABA release; 2. glucocorticoids elicit retrograde endocannabinoid release from PVN neurons by activation of a postsynaptic G protein-coupled receptor and lipid messenger signaling cascade; 3. the endocannabinoid-mediated changes in glutamate and GABA release in the PVN are mediated by presynaptic, G protein- and protein kinasedependent signaling mechanisms. These studies will reveal for the first time the site and physiological mechanisms of fast glucocorticoid actions in the hypothalamus. Fast glucocorticoid feedback in the hypothalamus plays a critical role in the organism's holistic response to stress, and understanding the mechanisms of glucocorticoid actions in the hypothalamus will provide important cellular targets for the treatment of HPArelated pathologies. Furthermore, the glucocorticoid-endocannabinoid link opens interesting possibilities for interactions between hypothalamic function and the cannabinoids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERACTIONS
ADRENAL
REGENERATION--
IMMUNO-ENDOCRINE
Principal Investigator & Institution: Engeland, William C.; Professor; Surgery; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2004 Summary: The overall hypothesis is that adrenal regulation is dependent on a sequence of early cellular events that are characterized by phenotypic plasticity and mediated by interaction between local inflammatory and circulating endocrine factors. To test this hypothesis, three major questions will be addressed. First, what is the mechanism for ACTH-induced promotion of adrenal regeneration? Experiments will delineate the effect of ACTH suppression on phenotypic and proliferative changes in regenerating adrenals. Changes in expression of mRNA and protein for cytochrome P450 and aldosterone synthase, a P450 11beta-hydroxylase, will be used as phenotype markers of glomerulosa and fasiculata cells, respectively. Proliferation of specific cell phenotypes
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will be monitored using double-label immunohistochemistry that induces proliferation markers. Changes in adrenal melanocortin-2 receptor mRNA and protein will be examined using RNase protection and western analysis, respectively; immunohistochemistry will assess the cellular distribution of the receptor. Second, does the renin-angiotensin (AT) system act to suppress regeneration? Since AT upregulates adrenal P450 aldosterone synthase and promotes expansion of zona glomerulosa, studies will determine the role of specific AT receptor subtypes in regeneration using antagonists of the AT-1 and AT-2 receptors. Experiments will characterize the distribution and binding of AT-1 and AT-2 receptors in regenerating adrenals. Since AT has been implicated in models of fibrosis, studies will assess whether AT produces adrenal fibrosis. Third, what components of inflammatory responses affect adrenal regeneration? Since both adrenal and inflammatory cells can synthesize cytokines, the phenotype of cells expressing cytokine activity during regeneration will be delineated. Cytokines identified in regenerating adrenals including interleukin-1, interleukin-1 receptor antagonist, interleukin-18, macrophage migration inhibitory factory and transforming growth factor-beta will be examined in vitro. The effect of specific cytokines on adrenal cell differentiation and proliferation will be defined using shortterm cultures of adrenal capsules with adherent cortical cells; potential cytokine modulation of ACTH and AT receptors will be evaluated. It is proposed that corticosteroids affect macrophage secretory activity at the site of adrenal inflammation. Studies using cultured regenerating adrenals or co-cultures of macrophages and adrenal capsules will assess macrophage-adrenal interactions. Since ACTH and AT may affect regeneration indirectly by altering the local inflammatory response, experiments will assess adrenal cytokine mRNA expression after in vivo blockade of ACTH or AT receptors. The proposed experiments should delineate the interaction between local inflammatory and endocrine factors responsible for adrenal regeneration and offer new perspective on injury-induced processes that result in tissue regeneration or fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL AND STRESS: INTERACTIVE EFFECTS Principal Investigator & Institution: Weinberg, Joanne K.; Professor; University of British Columbia 2075 Wesbrook Pl Vancouver, Bc Timing: Fiscal Year 2003; Project Start 01-AUG-1988; Project End 31-MAY-2008 Summary: (provided by applicant): The ability to respond to stress is an important basic adaptive mechanism, and hypothalamic-pituitary-adrenal (HPA) activation is a central component of this response. In the short term, stress-induced increases in corticosteroids (CORT) enable the organism to respond to and cope with the stressor. However, prolonged HPA activation can result in adverse physiological and behavioral consequences that can compromise health and even survival. Therefore, early life events that result in greater reactivity to stress and a lifetime of increased levels of CORT can increase the vulnerability to illnesses later in life. Our data demonstrate that 1) prenatal ethanol (E) exposure reprograms the fetal HPA axis and the central components that regulate HPA activity such that HPA tone is increased throughout life; 2) the change in set point of HPA activity appears to be mediated by alterations at multiple levels of the axis and under both basal and stress conditions; 3) E males and females show different patterns of response to stressors, indicating a marked sexual dimorphism in fetal ethanol effects and a possible role for the gonadal steroids in mediating HPA hyperresponsiveness. It appears that the balance between HPA drive and feedback is differentially altered in E males and females. A change in the balance between drive and feedback impairs the ability to maintain homeostasis, and progressively creates a
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condition of disturbed neuroendocrine regulation and behavioral adaptation. In turn, these changes have implications for vulnerability to illnesses, as noted, and for the development of secondary disabilities such as mental health and behavior problems in children with FAS. The proposed research will continue our study of the mechanisms underlying HPA dysregulation in E animals, and will extend our focus to an examination of mechanisms underlying the sex differences observed. The Specific Aims are: 1) to investigate further the mechanisms underlying the increased HPA responsiveness and altered HPA regulation observed in E animals; and 2) to investigate the modulatory influences of the gonadal steroids in the differential HPA responsiveness of E males and females compared to their control counterparts. The data from these studies will significantly advance our understanding of the long term and far reaching consequences of prenatal ethanol exposure on health and well-being, and will have important implications for the development of interventions and treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALVEOLAR HOST DEFENSE TO PNEUMOCYTIS CARINII Principal Investigator & Institution: Martin, William J.; Dean; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by the applicant): Pneumocystis carinii is the prototypical opportunistic pathogen in the lung. P. carinii pneumonia only occurs with profound immunosuppression that is often characterized by functional or absolute deficiencies in T and B lymphocytes. Alveolar macrophages (AMs) are the resident immunoregulatory cells of the alveolar spaces and are responsible for clearance of P. carinii organisms from the lung. The same factors that induce immunosuppression such as infections (HIV) or drugs (cytotoxic therapy or corticosteroids) directly and indirectly impair AM function and their ability to clear opportunistic infection such as P. carinii. Important immunomodulators that activate AM function include cytokines e.g. interferon-gamma (IFN-g) or tumor necrosis actor-a (TNF-a) are often deficient during immunodeficiency. Multiple studies have demonstrated the importance of T and B lymphocytes in the host response to P. carinii, often by reconstituting these cells into immunodeficient animals and restoring host defense. The critical role of the AM in the response is often assumed or ignored. We have developed new experimental approaches to assess the critical role of the AMs in vivo in alveolar host defense. This proposal will test the following hypothesis: Host susceptibility to infections such as P. carinii is due in part to deficiencies in AM function and factors that regulate AM function; conversely, correction of these defects will restore normal alveolar host response and control infection. The Specific Aims will include: I.To demonstrate that reconstitution of normal or activated AMs will restore local alveolar host defense in recipient SCID or immunodeficient mice; 2. To determine if reconstituted AM significantly enhance attachment/phagocytosis/killing of P. carinii and control of alveolar infection/pneumonia; 3. To determine the role of proinflammatory cytokines on the ability of reconstituted AMs to attach/phagocytose/kill P. carinii and to control alveolar infection/pneumonia; 4. To determine if ex vivo gene therapy to AMs corrects immune deficiencies in alveolar host defense and controls P. carinii alveolar infection/pneumonia. If successful, these studies may suggest it is possible to restore local alveolar host defense in an immunodeficient host despite ongoing systemic immunosuppression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANDROGEN-INDEPENDENT PROSTATE CANCER: MECHANISMS & TREAT Principal Investigator & Institution: Feldman, David; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: This proposal will investigate mechanisms of progression from androgendependent to androgen-independent prostate cancer (AIPC). Our hypothesis is that one mechanism for AIPC development is mutations in the androgen receptor (AR) that widen its ligand binding specificity, and allow non-androgens to bind to and activate it, thus stimulating prostate cancer (PCa) growth. This sub-group of AIPC is therefore dependent on the AR and we refer to this pathway as the promiscuous AR. Examples include the ARs in LNCaP cells (mutation T877A), and MDA PCa cells (mutations T877A and L701H). Although often referred to as androgen-dependent, these cells have promiscuous ARs that are androgen-responsive but not dependent on androgens since flutamide and other steroids can stimulate their growth. The grant has 3 Specific Aims. Aim I will further evaluate MDA PCa 2a and 2b cells that we have recently described as a cause of AIPC due to a promiscuous AR that responds to corticosteroids (ARccr). We will further characterize the steroids that bind to ARccr and develop treatment strategies to block or suppress the ARccr. We will investigate the frequency of the L701H mutation and other AR mutations that cause the promiscuous AR phenotype in metastatic specimens. Finally, we will investigate the pattern of gene regulation by androgens and corticosteroids via the ARccr using cDNA microarray technology. In Specific Aim II we will study a novel treatment strategy for AR-dependent AIPC. We hypothesize that molecules that can selectively down-regulate AR (SARDs) will be therapeutically useful in treating AR-dependent AIPCs. We have identified a number of hormones and ligands with this activity. In Aim II we will further identify, characterize and elucidate the mechanism of action of SARDs as well as demonstrate their ability to diminish growth stimulation of AR- dependent AIPC cells. In Specific Aim III we will employ two in vivo models to investigate the treatment strategies developed in Aims I and II. Model 1 will employ classic xenografts in nude mice. Model 2 is a new approach using luciferasetransfected PCa cell xenografts that can be observed in live mice with a charge coupled device camera. The bioluminescent model will be a major improvement over current xenograft approaches providing repeatable, quantitative imaging of prostate cancer progression that can detect microscopic metastases. In conclusion, we propose in vitro and in vivo experiments to investigate the mechanism of transition of PCa from androgen-dependent to AIPC, focusing on mutations in the AR and treatment strategies to prevent the growth of AR-dependent PCa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTERIOR PHARMACOLOGY
OCULAR
SEGMENT
PHYSIOLOGY
AND
Principal Investigator & Institution: Kaufman, Paul L.; Professor of Ophthalmology and Visual Sc; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-1979; Project End 31-AUG-2006 Summary: (provided by applicant): This project will characterize: functional/structural responses of the monkey aqueous human formation/drainage apparatus to pharmacologic probes; pathophysiology of deviations from normal function/structure produced by long-term antiglaucoma drug treatment; the role of cholinergic/adrenergic
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innervation in normal function, structure, their responses to pharmacologic agents, and deviations from normal produced by long-term antiglaucoma drug treatment; cytoskeletal, cell junctional, and extracellular matrix interactions of human trabecular meshwork and ciliary muscle cells to pharmacologic and biologic probes; the effect on aqueous outflow of relevant proteins encoded by genes delivered to the anterior chamber. Aqueous formation and drainage will be determined by perfusion and fluorophotometry. Accommodation will be stimulated by cholinergic agonists or a midbrain electrode and determined by coincidence refractometry. The ciliary muscle will be disinserted to identify primary drug effects on the trabecular meshwork. Parasympathetic denervation will be induced by ciliary ganglionectomy or panretinal photocoagulation, sympathetic denervation by superior cervical ganglionectomy. The effects of cholinergics, adrenergics, cyclic nucleotides, G-protein activators, hormones, peptides, prostaglandins, cytoskeletal agents, calcium channel blockers, cannabinoids, ionophores, carbonic anhydrase inhibitors, corticosteroids, and other compounds will be assessed in previously untouched, autonomically denervated, ciliary muscle disinserted, and long-term antiglaucoma drug-treated eyes. Agonists, antagonists, mediators, metabolites, and protein and RNA synthesis inhibitors will be used, and interactions among drug classes sought. Aqueous formation and drainage will be evaluated after injection of vectors containing genes whose products may affect aqueous humor dynamics. In vitro responses of trabecular meshwork and ciliary muscle cells to pharmacologic and biologic probes will be studied using immunohistochemistry to examine cytoskeletal and cell junctional changes. Structural parameters in the meshwork and ciliary muscle/processes of intact eyes will be evaluated by light/electron microscopy, immunohistochemistry and quantitative morphometry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARTHRITIS AND OUTCOMES IN CHRONIC DISEASES Principal Investigator & Institution: Ward, Michael M.; Associate Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 08-APR-2002; Project End 31-DEC-2006 Summary: Rheumatoid arthritis (RA) and osteoarthritis (OA) and their treatments may affect patients' quality of life not only by their effects on the musculosketal system, but also by collateral effects on other organ systems. Morbidity and mortality from cardiovascular diseases may be increased by physical inactivity, systemic inflammation and possibly by treatment with corticosteroids, methotrexate, or non-steroidal antiinflammatory drugs (NSAIDs) selective of cyclooxygenase-2. Use of NSAIDs may decrease the risk of colorectal cancer, while use of immunosuppressive medications may increase the hematological malignancies. This project proposes a series of cohort studies based on longitudinal data on approximately 3500 patients with RA and 2500 patients with OA that will: 1) define the risks of morbidity and mortality from acute myocardial infarction and stroke among patients with RA and OA; 2) determine the relative contributions of systemic inflammation, musculoskeletal morbidity, and medications to the risk of myocardial infarction and stroke; 3) define the risks of morbidity and mortality from colorectal cancer among patients with RA and OA; 4) determine the contribution of NSAID use to the risk of colorectal cancer in these patients; 5) define the risks of morbidity and mortality form hematologic malignancies among patients with RA; and 6) determine the contribution of immunosuppressive medications and anticytokine drugs to the risk of hematologic malignancies. Knowledge of the reciprocal relationship between chronic arthritis and comorbid conditions will provide a more complete understanding of the health consequences of RA and OA, identify risk factors
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for comorbid conditions, suggest strategies for intervention, and more fully characterize the long-term consequences of treatment. Medication choices may therefore be made with more precise information. Many of the most important outcomes of arthritis and it treatments may come from their indirect effects on other chronic illnesses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASTHMA CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Leone, Frank T.; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-AUG-2004 Summary: This application proposes to continue the participation of investigators at Thomas Jefferson University in an interactive network of six centers (the Asthma Clinical Research Network or ACRN ) in conducting studies of novel therapeutic approaches to asthma and in disseminating findings to the practicing community. The need for such a network was suggested by epidemiological data showing increases in mortality, morbidity, prevalence, and costs of asthma, by clinical and basic research studies showing that asthma is linked to inflammation in the airways, and by the accelerating rate of development of potentially effective, but also potentially costly treatments for asthma. Defining the place of these therapies was seen as requiring collaborative, multi-center studies examining large numbers of subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an infrastructure to meet this need and has added another center at Harlem Hospital in New York, which serves a predominantly minority population. The ACRN has completed studies of the effects of regular beta-agonist use in mild asthma ( BAGS ) and of the efficacy of the anti-inflammatory agent, colchicine, as an alternative to an inhaled corticosteroid in moderate asthma. Now underway are two additional trials comparing the effects of a long-acting beta-agonist, an inhaled corticosteriod, and the combination of the two in altering clinical and physiologic outcomes, and airway inflammation in moderate or severe asthma. A fifth study, establishing doses of different inhaled corticosteroids with equivalent effects on cortisol secretion, is imminent. Completed trials as well as 10-12 ancillary studies designed to improve the performance of clinical research have been presented at meetings of the ATS, ACCP, and AAAAI. Three of these studies have thus far been published in peer- reviewed journals. The ACRN has also reported the results of a subgroup analysis of subjects in the BAGS study showing that subjects with different genotypes for the beta-adrenergic receptor are differently affected by regular use of albuterol. This application proposes continued participation of the Jefferson Center in the multicentered, collaborative trials of the ACRN. Proposed studies include a comparison of the efficacy of doses of different inhaled corticosteriods with equal systemic effects (as estimated from the study described above), a prospective study of the effects of regular use of an inhaled beta-agonist in subjects stratified by genotype for the beta-adrenergic receptor, and a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteriods in subjects with mild or moderate persistent asthma. Other planned studies are also briefly discussed, with the understanding that they could be modified or replaced in response to new information, new therapies, or changing clinical research priorities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASTHMA CLINICAL RESEARCH NETWORK (ACRN) Principal Investigator & Institution: Martin, Richard J.; Department of Medicine; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206
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Corticosteroids
Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-AUG-2004 Summary: This application proposes to continue the participation of investigators at National Jewish Medical and Research Center in an interactive network of six centers, the Asthma Clinical Research Network (ACRN) in conducting studies of novel therapies for asthma and in disseminating findings to the practicing community. The need for such a network was suggested by increases in the mortality, morbidity, prevalence, and costs of asthma, by research studies showing that asthma is linked to airway inflammation, and by the accelerating rate of development of potentially effective, but also potentially costly treatments. Defining the place of these new therapies was seen as requiring collaborative, multi-center studies examining subjects reflecting the diversity of the U.S. population. In its first 5 years, the ACRN established an interactive infrastructure and added a research site at Harlem Hospital, New York, which serves a predominantly minority population. The ACRN completed and published trials of the effects of regular use of a Beta- agonist in mild asthma ("BAGS") and of the efficacy of colchicine as an alternate to an inhaled corticosteroid (ICS) in moderate asthma. It is now conducting trials comparing a long-acting Beta-agonist, an ICS, and the combination of the two in moderate to severe asthma. We are about to start a 5th study to establish doses of different ICS with equivalent effects on cortisol secretion. These studies have been presented at meetings of the ATS, ACCP, and AAAAI, as have 10-12 ancillary studies analyzing the performance of clinical research. The ACRN has also reported its findings from subgroup analysis of the "BAGS" study: that subjects with different genotypes for the Beta-adrenergic receptor are differently affected by regular use of albuterol. This application proposes continued participation of the National Jewish Asthma Clinical Research group in the multicentered, collaborative trials of the ACRN. The studies proposed include a comparison of the clinical efficacy of doses of different inhaled corticosteroids with equal systemic effects, a prospective study of regular use of an inhaled Beta-agonist in subjects stratified by genotype for the Betaadrenergic receptor, a study of the efficacy of a leukotriene pathway antagonist in enabling reduction or elimination of inhaled corticosteroid therapy in subjects with mild or moderate persistent asthma, and other studies illustrated briefly in this application, but modified or replaced by the ACRN Steering Committee in response to new information or the release of new forms of therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASTHMA CLINICAL RESEARCH NETWORK-WASHINGTON UNIVERSITY Principal Investigator & Institution: Castro, Mario; Associate Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The overall goal of this application is to optimize asthma management for the majority of patients with asthma. Our application will utilize the strengths of the Asthma Clinical Research Network (ACRN) to address two common clinical issues: 1) What is the best method of asthma self-management when using an asthma action plan? And 2) What is the best treatment to prevent an asthma exacerbation during a respiratory tract infection? There is currently insufficient evidence to support the use of written asthma action plans that are peak flow- or symptom-based in improving health care utilization, symptoms or lung function. For that reason, our first proposed protocol, "Asthma Action Plans improve Asthma Control" (The AAPAC Trial), (Aim I) will investigate the effectiveness of symptom-based and peak flow-based written asthma action plans in improving asthma control in adults with persistent
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asthma. Furthermore, the AAPAC trial will address whether either asthma action plan is better than medical management alone. A second important clinical question addresses the treatment of asthma exacerbations due to the most common etiology - respiratory tract infections. The majority of respiratory tract infections which lead to exacerbations of asthma in adults and children are caused by viruses when sensitive detection methods are utilized. It is unclear what is the optimal therapy that health care providers should recommend to their patients to prevent an asthma exacerbation, when the patients start to experience upper respiratory tract infection symptoms. In that regard, our second proposed protocol for the ACRN, "Preventing Respiratory TrACT InfectioninduCed Asthma exacerbations protocol" (The PRACTICAL Trial), (Aim II) will investigate if prompt use of corticosteroids (either inhaled or oral) following the onset of respiratory tract infection symptoms will prevent or ameliorate an asthma exacerbation. We believe these protocols are ideal studies for the ACRN, as they evaluate treatment strategies for common and pertinent clinical issues, necessitate large numbers of comparable patients, and require standardized treatment protocols. Furthermore, by design, both of these trials can be completed in relatively short time frame (e.g. 12-18 months) and the information obtained can then be rapidly disseminated to health care professionals and the public. We propose that it is only through such a collaboration that important questions regarding current and novel therapies and management of asthma can be answered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANNABINOIDS ADRENAL AXIS
AND
THE
HYPOTHALAMIC-PITUITARY-
Principal Investigator & Institution: Murphy, Laura L.; Associate Professor; Physiology; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-MAY-2004 Summary: The long-term objectives of this proposal are to advance our knowledge of the physiological effects of marijuana abuse and to elucidate the neuroendocrine function of the endogenous cannabinoid system. This proposal will focus on the effects of cannabinoids on the hypothalamic-pituitary-adrenal (HPA) axis, a system which plays a critical role in coordinating the neuroendocrine response to stress. The specific aims of this proposal address the ability of cannabinoids to stimulate adrenocorticotropin hormone (ACTH) and corticosteroid release in the female and understanding the role of corticotropin-releasing hormone (CRH) in this response. Furthermore, the role of CRH in the ability of cannabinoids to decrease luteinizing hormone (LH) and induce catalepsy and alterations in feeding behavior will be investigated. Moreover, the site and mechanisms by which cannabinoids elicit their effects on CRH release and the modulation of the CNS responsiveness to cannabinoids by corticosteroids will be investigated. Initially, the role of cannabinoid receptors in the ability of marijuana to alter hormone secretion and feeding behavior will be determined by examining the effects of specific cannabinoid receptor agonists (levonantradol,methanandamide) and antagonists (SR141716A) on ACTH, corticosteroid and LH secretion and feeding behaviors in OVX rats. Secondly, the role of CRH in the ability of THC to alter hormone release, feeding behavior and catalepsy will be determined by measuring hypothalamic CRH gene expression following acute treatment with cannabinoid receptor agonists. The role of CRH as mediator of cannabinoid effects will also be determined utilizing a CRH receptor antagonist (DPheCRH12-41) and studying its ability to block cannabinoid action. Thirdly, the site and mechanism of cannabinoid action in the stimulation of the HPA axis will be determined
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by addressing the role of serotonin in the ability of cannabinoids to affect the HPA axis and by examining the hypothalamus, hippocampus, amygdala, raphe nuclei) as potential sites of cannabinoid action. Lastly, the ability of glucocorticoids to modulate cannabinoid actions on the HPA axis will be investigated. Our findings using female rats will not only address the potential neuroendocrine role of endogenous cannabinoids, but will provide new information on how cannabinoids modulate the HPA system; activation of which may have significant consequences on the endocrine, reproductive and immune systems of the human marijuana user. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHILDHOOD PHARMACOGENETICS
ASTHMA:
EARLY
PREVENTION
AND
Principal Investigator & Institution: Martinez, Fernando D.; Professor of Pediatrics; Pediatrics; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Our group has recently demonstrated that early onset asthma (before age 3) is associated with more severe symptoms and more significant deficits in lung function (not readily reversible with bronchodilators) at age 11 than late onset asthma. In Project 1 of this application to the Pediatric Asthma Clinical Research Network, the potential role of inhaled corticosteroids in modifying the natural history of early onset asthma will be assessed. Children at high risk for asthma aged 24-47 months will be treated with either inhaled corticosteroids or placebo for a period of 18 months. The main outcome variables will be assessed during a one year observation period off trial drug immediately following the treatment phase. Number of symptom-free and controllerfree days will be the main outcome variable. In addition, maximal flows obtained from partial expiratory flow volume loops and airway responses to cold dry air will also be compared in both treatment groups. These techniques have been successfully developed by our group for use in pre-school children. Genetic variants in the beta-adrenergic receptor gene have been described by Liggett et al, and we recently reported that one such polymorphism (glycine/arginine in residue 16) was strongly associated with response to albuterol in children. Project 2 will assess the influence of these genetic variants on response to standardized therapy among subjects with mild persistent and mild intermittent asthma. We expect to find that carriers of the Gly-16 variant of this gene will require more beta agonist and hence receive more control medication and require more inhaled corticosteroids than carriers of the Arg-16 variant. Our group is uniquely qualified to contribute to PACRN. We have a long experience in long-term clinical and epidemiological studies of childhood asthma, especially among infants and pre-schoolers. We have also established strong collaborative links with community health care providers especially those involved in the primary care of asthma among our Hispanic community in Tucson. Finally, we have a very active program in the genetics and pharmacogenetics of asthma that may prove very important for the long-term objectives of PACRN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHILDHOOD ASTHMA: INITIATION AND INTERVENTION Principal Investigator & Institution: Lemanske, Robert F.; Professor of Medicine and Pediatrics; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004
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Summary: Investigators that constitute a pediatric asthma clinical research network will have an extraordinary opportunity and responsibility to advance the field in the diagnosis, pathogenesis, and treatment of children and adolescents with asthma. This research team should have the courage and insight to be both innovative and aspiring in the development of protocols to address questions currently unanswered due to shortcomings in trial design in previously conducted studies. Clinical trials designed to evaluate a particular form of treatment for childhood asthma need first, to recognize the potential for the intervention to modulate either the initiation of the asthmatic phenotype or the induction of asthma exacerbations once the syndrome has become established; and second, to comprehensively evaluate the short- and long-term consequences of any treatment intervention. Ideally, appropriately designed protocols should provide insight into selecting the right child, to treat at the right time, and with the right medication. To address these needs, we propose two protocols that bookend the extremes of important questions in pediatric asthma in age groups (infancy and adolescence) in which asthma therapy has been incompletely examined. In the first protocol, we propose to evaluate the safety and efficacy of two types of long term controller therapies (an inhaled corticosteroid and a leukotriene receptor antagonist) in children divided into two separate phenotypic groups based on risk factors previously demonstrated to be associated with persistent (asthma) versus transient wheezing. In the second protocol, we propose to evaluate the effects of inhaled corticosteroids during a period of growth and development that many clinicians are concerned about (adolescence), but a time period that has never been critically examined. Although both protocols are challenging, we consider them to be potential examples of the types of comprehensive clinical investigations a pediatric oriented network should be capable of developing and conducting in a way that will provide clinically relevant and useful information, while at the same time establishing and maintaining acceptable standards of safety in these age groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL CENTER FOR BILIARY ATRESIA: ETIOPATHOGENESIS A* Principal Investigator & Institution: Bezerra, Jorge A.; Associate Professor of Pediatrics; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to develop a Biliary Atresia Clinical Center to perform translational research focused on diagnosis, pathogenesis, and novel therapeutic modalities for biliary atresia and neonatal hepatitis. These disorders are the main causes of neonatal cholestasis, with biliary atresia accounting for -50% of the indications for liver transplantation in children. The application is a logical extension of the long-standing mission of the applicant Center to provide exceptional care to any child with liver disease through comprehensive care and research. To pursue this mission, a clinical service focused exclusively on pediatric liver disease was created in 1985; since, then, we have served as a referral center for regional medical groups and institutions. We also performed clinical and patient-directed laboratory research to define specific causes of neonatal hepatitis and to explore novel therapeutic modalities for affected infants. Recently, we applied functional genomics to identify immunologic pathways that may regulate pathogenesis of biliary atresia. Despite these accomplishments, we recognize that further advances will depend directly on the access to a large patient population in a prospective manner for adequately powered studies. Therefore, we set two goals for the applicant Center: 1) to establish and maintain the
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infrastructure of a Clinical Center that will work in collaboration with other centers of the Biliary Atresia Clinical Research Consortium, and 2) to actively use the resources provided by the consortium to carry out studies on children with biliary atresia and neonatal hepatitis. To accomplish these goals, we propose an administrative structure jointly shared by medical and surgical faculty of the Center, a network of regional collaborators that will assure access to patients, and a database to gather clinical and laboratory information based on the natural history of biliary atresia. Using a model of translational research that is focused on the child with biliary atresia, we propose two studies to be carried with the approval by the Research Consortium. The first is a shortterm study applying basic science technology to further defines the pathogenesis of this disease. The second is a 3-year open-label randomized study to establish the efficacy of corticosteroids in improving biliary flow following surgical portoenterostomy in infants with biliary atresia. Execution of these studies and access to a critical amount of clinical information and serum/tissues will facilitate research and generate hypotheses on pathogenesis and optimal treatment for children with biliary atresia and neonatal hepatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL CENTER IN COPD Principal Investigator & Institution: Bailey, William C.; Professor and Director; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is a serious public health problem responsible for more than 500, 000 hospitalizations, 100,000 deaths, and $15 billion in direct costs of medical care in the United States each year. We propose to form a collaborative COPD CRN Clinical Center at the University of Alabama at Birmingham (UAB) and the Birmingham Veterans Affairs Medical Center (BVAMC). The UAB/BVAMC Clinical Center will be headed by, Drs. William C. Bailey and J. Allen D. Cooper. The proposed investigators and their research staff have extensive experience in recruitment and retention for clinical trials, as well as study design and implementation. The collaborative effort between UAB and the BVAMC will allow us to quickly and efficiently recruit large numbers of COPD patients for clinical research studies. In addition, the UAB/BVAMC COPD Clinical Center will have access to a large network of experts at the University of Alabama at Birmingham who can assist in the design and implementation of clinical trials. The UAB/BVAMC Clinical Center proposes two studies aimed at enhancing treatment for moderate-to severe COPD. The first study will examine measures of inflammation and responsiveness to bronchodilator challenge, responsiveness to systemic steroid treatment, and responsiveness to inhaled steroid treatment. This study may provide a new method for identifying subgroups of COPD patients who are most likely to respond to inhaled corticosteroids. The second project will examine the causes of poor responsiveness to the pneumococcal vaccine with the long term goal of using this information to reduce pneumococcal infections and related exacerbations in COPD patients. The UAB/BVAMC Clinical Center also proposes a Clinical Research Skills Training Core. Dr. J. Allen D. Cooper, the Director for fellowship training in Pulmonary and Critical Care Medicine at UAB, will head this core. Trainees will be funded for a total of two years and will be required to enroll in one of the UAB K30 Clinical Research Curriculum Development Award components (either the Clinical Research Training Program or the Master's of Science in Public Health in Clinical Research). Trainees will also receive funding for a pilot project, which will be developed and conducted under the
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supervision of the Training Core Investigators. These Investigators have expertise in COPD, Clinical Research and Study Design, Behavioral Science, Epidemiology, and Statistics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITION, STEROIDS AND IMAGING IN CUSHINGS DISEASE Principal Investigator & Institution: Starkman, Monica N.; Associate Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 27-SEP-1997; Project End 31-AUG-2004 Summary: (Adapted from applicant's abstract): Dysregulation of the hypothalamicpituitary-adrenal axis resulting in hypercortisolemia is present in a significant proportion of the aged and in neuropsychiatric conditions such as Alzheimer's Disease and Major Depressive Disorder. However, the relationship of this dysregulation to clinical symptoms is still insufficiently understood. Patients with CD exhibit hypercortisolemia and develop disturbances in mood, sleep, libido, and cognition. The investigator's hypothesis is that steroid elevations in these various conditions have important neuroactive effects. The investigator's objective is to examine the role of steroids in the pathophysiology of behavior by exploiting the fact that patients with CD are a unique model providing sustained exposure to high concentrations of endogenous steroids over a long-term period. The studies proposed focus on abnormalities in cognition. Studies in animals indicate that elevated corticosteroids result in toxicity to the hippocampus. This is one likely mechanism for the manner in which glucocorticoids elicit cognitive dysfunction. The investigator proposes to use MRI of the brain together with neuropsychologic (NP) testing to investigate such a mechanism in humans. Evidence is accumulating that other steroids such as androgens play key roles in modulating neuronal excitability. In many patients with CD, testosterone and dehydroepiandrosterone (DHEA) are also markedly elevated. The investigator's specific aims are to: 1) Study in fine detail cognitive dysfunction in patients with CD using sensitive, specific tests with graded levels of difficulty to probe for subtle as well as easily-elicited abnormalities. 2) Examine, prior to treatment, MRI-determined hippocampal formation (HF) volume in patients with CD, and compare to the volume of age, sex, and education-matched normal controls. The investigator will examine specificity for region by measuring and comparing the volumes of caudate head (CH), frontal lobe and anterior temporal lobe (ATL). 3) Examine associations between severity of hypercortisolemia, NP impairment and HF volume. The volumes of CH, frontal and ATL will be used as comparison regions. 4) Repeat NP testing and MRI one and two years following treatment of CD, in order to determine if changes in cognition and HF volume are reversible. Associations between changes in volume and cognitive test scores will be studied. 5) Examine the potential modulatory role of the androgens testosterone and DHEA, co-secreted with cortisol, on tests of attention, learning and memory. Hypercortisolemia occurs with aging and in several important neuropsychiatric diseases. The studies proposed will help advance knowledge about the role of the glucocorticoid cortisol in the mechanisms contributing to cognitive dysfunction in these conditions. The rationale for developing protective drugs such as site-specific glucocorticoid receptor antagonists or excitatory amino acid suppressors would be strengthened. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COOPERATVIE MULTI CENTER MATERNAL-FETAL UNITS NETWORK Principal Investigator & Institution: Ramin, Susan M.; Associate Professor with Tenure; Ob, Gyn and Reproductive Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: The Division of Maternal-Fetal Medicine at the University of Texas- Houston Medical School has a major commitment to evidence-based medicine and the performance of randomized clinical trials. Members of this division have experience in performing such trials in the areas of corticosteroids for fetal maturation, preterm premature rupture of the membranes, effects of anesthesia/analgesia in labor and method of delivery, and obstetrical infections. There is an established clinical research unit in place, including a research coordinator, data management systems, personnel, facilities and equipment. There is more than an adequate population base to perform randomized clinical trials and this obstetric population base is diverse in socioeconomic, racial and ethnic character. There is a very large obstetric network, which provides a large number of high-risk pregnancies to further support the performance of randomized clinical trials. The Division of Maternal-Fetal Medicine has both the capability and University support to provide protected research time, as well as the capability, desire and commitment to work with other centers in collaborative research regarding pregnancy outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COPD EXACERBATIONS: PHARMACOGENETIC APPROACHES TO THERA* Principal Investigator & Institution: Reilly, John J.; Clinical Director; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The proposal "COPD Exacerbations: Pharmacogenetic Approaches to Therapy" presents the commitment of an established group of clinical investigators at Harvard Medical School with a long-standing interest in COPD to participate as a Clinical Center in the proposed COPD Clinical Research Network and to work with other Clinical Centers to create and implement protocols directed at improving the care of patients with COPD. The applicants propose to recruit patients with COPD from patients admitted to hospitals for treatment of COPD, established pulmonary practices in major teaching hospitals, and an associated large health care provider network. Strategies for recruitment include the use of several large clinical databases that have identified patients with COPD. The scientific focus of the proposal is on the prevention and treatment of exacerbations. Exacerbations of COPD, defined as an increase in shortness of breath and an increase in the amount and/or purulence of sputum, are a major determinant of patient quality of life and account for substantial health care expenditures. The applicants propose 2 protocols for consideration by the network; one is directed at treatment of acute exacerbations with inhaled corticosteroids and the second at prevention of exacerbations by use of a leukotriene inhibitor. The first protocol offers the potential advantage of a therapy that has fewer complications than current standard therapy with oral or intravenous corticosteroids. Patients will be randomized to either inhaled or oral steroids for therapy of exacerbation. The primary outcome will be time to next exacerbation. The second examines the role of a class of medications, leukotriene inhibitors, that has been
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demonstrated to be beneficial in asthma but have not been systematically evaluated in patients with COPD. Patients will be randomized to receive zileuton or placebo for 12 months. Frequency of exacerbations will be the primary outcome. Both protocols have associated pharmacogenetic studies designed to identify subsets of patients likely to respond to the particular class of medications. These analyses are intended to provide a strategy for more specific targeting of therapy within the heterogeneous population of patients with COPD, estimated at approximately 18 million people in the U.S. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CLINICAL FACILITY Principal Investigator & Institution: Leopold, Donald A.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: Chronic rhinosinusitis is a major health problem that affects approximately 15% of the US population. It is the hypothesis of this Program Grant that chronic rhinosinusitis represents a disease of epithelial cell and mucosal dysfunction. Together the 3 Projects that comprise this program provide an integrated approach to evaluate if this epithelial dysfunction arises as a result of an inherent genetic defect(s), environmental influences, or a combination of the two. This CORES serves as an essential clinical resource and will provide support for each of the 3 projects by pursuing the following aims: We will recruit and characterize the chronic rhinosinusitis patients that are required by all of the Projects, as well as the healthy, normal subjects and patients with perennial allergic rhinitis that are required as control populations for the second and third projects. We will assist the second project in ensuring the aggressive follow up of subjects recruited to assess the role of viral infections in the induction and recurrence of chronic rhinosinusitis; and of corticosteroids in reducing disease recurrence after surgery. We will also provide the sinus mucosal biopsies required as part of this protocol. We will assist the first Project in surveying, by questionnaire, members of families that have inherited a mutation in the cystic fibrosis transmembrane regulator (CFTR), and will clinically characterize family members with a positive history to verify that they have chronic rhinosinusitis. Enrollment of these family members will also serve the needs of the third Project. We will clinically characterize obligate carriers of CFTR mutations (i.e. parents of cystic fibrosis patients), recruited by the first project who have a positive history by questionnaire to verify that they have chronic rhinosinusitis. We will continue to maintain, refine and update a relational database that is being used to record demographic and clinical information on patients with chronic rhinosinusitis who are recruited into our studies. The use of well characterized patients is critical to any attempt to examine the pathogenesis of chronic rhinosinusitis, or to test therapies that may improve the management of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPITHELIUM
CORTICOSTEROID
INDUCED
APOPTOSIS
IN
AIRWAY
Principal Investigator & Institution: White, Steven R.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The airway epithelium has a major role in maintaining airway homeostasis and may be damaged extensively in inflammatory diseases such as asthma. Environmental exposure to allergen may worsen asthma in part by causing epithelial
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cell shedding and cell death. Although denudation of bronchial epithelium is a cardinal feature of the pathology of asthma, the mechanisms underlying this phenomenon remain unknown. As part of their potent inflammatory effects in airways, corticosteroids induce apoptosis in migratory eosinophils and T-lymphocytes. New data from our laboratory suggest that corticosteroids can also induce apoptosis in airway epithelium, both in cultured cells and in animal models. As such, corticosteroids may possess a heretofore unrecognized adverse consequence: induction of epithelial cell apoptosis and prolongation of bronchial epithelial denudation. Continued epithelial damage may lead to the development of sub- epithelial fibrosis and chronic airway remodeling. The central hypothesis of our proposal is that corticosteroid treatment is deleterious to bronchial epithelial survival, even though it promotes resolution of airway inflammation. Our goal is to answer two specific hypotheses: 1) whether corticosteroids elicit epithelial cell apoptosis, and worsen epithelial cell apoptosis during allergen challenge; and 2) whether differentiation factors for epithelial cells counter corticosteroid-induced apoptosis. Specific assays to determine apoptosis both in culture and in airway and lung tissue sections will be used. Signaling mechanisms for initiation of apoptosis by corticosteroids will be examined by Western blot, fluorescent assays, and RT-PCR. The use of transfected human airway epithelial cells will determine whether differentiation factors, such as transforming growth factor-beta and cis-retinoic acid, attenuate apoptosis and speed repair. A mouse model will be used to demonstrate the effect of corticosteroid and differentiation factor treatment on epithelial cell apoptosis, repair and integrity in vivo. This model will help determine the interplay between airway inflammation and corticosteroid treatment on the genesis of epithelial damage. These experiments will demonstrate mechanisms by which epithelial cell apoptosis leads to impaired repair of the airway mucosa after injury. Demonstration that corticosteroids worsen epithelial cell apoptosis, shedding and death would suggest that at least one of the pathologic findings in chronic asthma may be a result of treatment for the disease. These data would help lead to new therapeutic ideas and modalities in the treatment of asthma to suppress inflammation while preventing mucosal damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING Principal Investigator & Institution: Lakoski, Joan M.; Professor; Pharmacology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JUL-2002 Summary: Depressive disorders are linked to impairments in the regulation of glucocorticoid and serotonin (5-HT) systems. Examination of depression in the elderly patient has revealed a role for the interaction of the adrenal hormone corticosterone and 5-HT receptors and may also underlie deficits in memory, learning and losses in ability to adapt to stress with aging. Our long term goal is to understand corticosterone and 5HT receptor interaction in the aging hippocampus and provide new clinical approaches for improving the treatment of depression and memory loss in geriatric patients. Using a corticosterone treatment paradigm, we will test the hypothesis that the cellular pharmacological characteristics of the 5-HT1A receptor subtype, as modulated by corticosteroids in the hippocampus, change with aging and loose responsiveness to this hormone, including losses in signal transduction. Electrophysiological, neurochemical and molecular biological approaches will be utilized in the female Fischer 344 rat (3, 12 and 18 mo) under several conditions of corticosterone hormone exposure
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(adrenalectomy plus low, moderate and high concentrations of hormone replacement) sham adrenalectomy or intact treatment. Aim 1 will utilize in vivo extracellular recording techniques in the chloral hydrate anesthetized rat chronically treated with corticosterone and evaluate neuronal responses to selective 5-HT1A receptor agonists with aging. Aim 2 will establish the effect of chronic corticosterone exposure on binding and gene expression characteristics of the 5-HT1A receptor in the aging hippocampus using radioligand binding, quantitative autoradiography and in situ hybridization techniques. Aim 3 will address signal transduction in the aging hippocampus mediating corticosterone and 5-HT receptor interactions. Chronic corticosterone administration effects on G protein levels will be examined by Western blot techniques and compared with assessment of age- associated declines in 5-HT1A receptor-mediated G proteincoupling. The results of these studies may lead to an indication that specific glucocorticoid antagonists may facilitate the onset of therapeutic efficacy for antidepressants in the elderly via actions at the serotonergic system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTICOSTEROIDS, STRESS AND LEYDIG CELL FUNCTION Principal Investigator & Institution: Hardy, Matthew P.; Senior Scientist; Population Council 1 Dag Hammarskjold Plaza New York, Ny 10017 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-DEC-2004 Summary: (Adapted from the applicant's abstract) Leydig cells contain glucocorticoid receptors and respond to glucocorticoid by decreasing their rate of testosterone production. Serum levels of glucocorticoid are increased during stress caused by a wide variety of conditions, including disease, exercise and psychosocial interaction. Based upon these facts, the applicant and other investigators hypothesize that declines in male reproductive function associated with stress are due in part to the direct inhibition of Leydig cells by glucocorticoid. Therefore, the applicant will test the hypothesis that rapid declines in testosterone occurring within two hours of acute stress are independent of luteinizing hormone and are directly mediated by glucocorticoid acting on Leydig cells. He will also investigate the physiological role of 11beta-hydroxysteroid dehydrogenase (11betaHSD) because this enzyme is abundantly expressed in Leydig cells and metabolizes glucocorticoid. Three Specific Aims are proposed. Aim (1) is to test for effects of glucocorticoid mediated by glucocorticoid receptors (GR) in Leydig cells, using both adrenalectomized rats and mice with a Leydig-cell-specific knockout of GR. Specific Aim (2) will define the consequences of stress for the Leydig cell. Aim (3) is intended to identify sustained effects of high glucocorticoid concentrations on Leydig cell steroidogenesis after exposure to stress in utero, perinatally or during adulthood. These studies would be the first to establish the extent of direct, GR-mediated glucocorticoid action on Leydig cells during stress. Other stress-induced factors such as nitric oxide and beta-endorphin will be monitored at the testis level because they may affect Leydig cell function independently and/or in addition to glucocorticoid. The hypothesis that 11betaHSD in Leydig cells is a key determinant of stress effects is supported by the fact that 11beta oxidation is the usual mode of 11betaHSD catalysis in Leydig cells from adults. The reverse is true of immature Leydig cells where the 11betareductase predominates. The balance of oxidative and reductive catalytic activity displayed by the type 1 isoform of the enzyme in Leydig cells may be adjustable by intracellular conditions, fine-tuning of glucocorticoid effects, affected by stress. Therefore, the applicant will also test for the existence of endogenous inhibitors in the testis that selectively modulate these opposing activities of 11betaHSD. Anticipated
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results would show that 11betaHSD is a critical intracellular regulator of testosterone production in Leydig cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTISOL AT MR MEDIATE FETAL PHYSIOLOGIC/GENOMIC EFFECTS Principal Investigator & Institution: Keller-Wood, Maureen E.; Professor and Chair; Pharmacodynamics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The overall goal of these studies is to test the hypothesis that for most of gestation, the concentrations of free cortisol in the fetus exert physiologic actions via the high affinity (corticosteroid type I) mineralocorticoid receptors (MR) rather than the lower affinity, but higher capacity, glucocorticoid receptors (GR). It is well established that the high levels of cortisol produced by the fetal adrenal at the time of delivery are important for normal organ maturation, and that these effects are mediated by GR. The presence of MR in fetal tissues as early as midgestation suggests that there may be effects of low concentrations of cortisol via MR, even before the time of fetal maturation. We will test whether cortisol action at MR receptors mediates effects on fetal volume through specific MR-target genes in the lung and/or kidney, and on hypothalamo pituitary-adrenal function via MR-target genes in the hippocampus. The relative activity of corticosteroids in the tissues will be related to plasma levels of corticosteroids, activity of 11beta-hydroxysteroid dehydrogenase and reductase activities (11betaHSD), levels of MR and GR in the tissue, and transactivation to alter gene expression. MR target genes, including the early response genes, Sgk and K-Ras, and more slowly induced genes for ENaC, Na/K ATPase and 5HT1A, MR and GR will be tested. To test this hypothesis, experiments were designed to: 1) Quantitate the protein, mRNA and relative occupancy by endogenous steroids of MR and GR, and activity of 11betaHSD in fetal tissues such as lung, kidney, heart, hippocampus, brainstem and pituitary in late gestation fetuses both before and after the time of fetal adrenal maturation (120-140d); 2) Test the effect of blockade of fetal MR receptors on physiologic actions known in the adult to be MR-mediated, renal function and ACTH secretion, and on a possible MR-mediated function in the fetus, lung liquid reabsorption; 3) Test for a relation between MR occupancy and these physiologic effects, and on the proposed target genes for MR action in hippocampus, kidney, and by analogy, fetal lung; 4) to compare the effect of combined MR and GR occupancy on these genes and physiologic actions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COX GENE REGULATION IN INTESTINAL MYOFIBROBLASTS Principal Investigator & Institution: Powell, Don W.; Professor of Medicine; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The general hypothesis of this grant proposal is that intestinal subepithelial myofibroblasts (ISEMF) are the source of soluble factors that modulate epithelial growth, differentiation, and repair and play a pivotal role in mucosal immunophysiology and cancer. Located at the interface between the epithelium and lamina propria, ISEMF modulate information transfer between these tissue compartments. Through elaboration of basement membrane components,
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prostaglandins (PGs). and growth factors, ISEMF modulate processes of epithelial cell growth, differentiation, and wound repair. One major pathway by which ISEMF influence epithelial and lamina propria cells is through the production of PGs by cyclooxygenase-2 (COX-2). Data indicate that the bulk of mucosal PG synthesis occurs in the lamina propria, possibly in ISEMF. Because COX-2 regulation appears to be different in the various cell types thus far studied, this proposed research will test the hypothesis that ISEMF are major sites of COX-2 expression and that pro- and antiinflammatory agents act in part by inducing or inhibiting COX-2 expression in ISEMF. Specific Aims: 1. Determine the mechanisms by which proinflammatory cytokines (IFN-gamma, TNFalpha, IL-1) and eicosanoids (arachidonic acid, various HETEs) induce COX-2 gene expression in ISEMF, 2. Analyze the mechanisms responsible for inhibition of COX-2 gene expression in ISEMF by antiinflammatory cytokines (IL-4, IL-13) and therapeutic corticosteroids, and 3. Characterize COX-2 expression in human ISEMF in situ and in primary ISEMF cultures from normal small intestine and colon and from various inflammatory diseases such as ulcerative colitis, Crohn's disease, and collagenous colitis and various neoplastic states such as adenomatous and hamartomatous polyps and both sporadic and familial adenomatous polyposis colon cancers. We will use an ISEMF cell line (18Co) isolated from human colon, reporter gene constructs containing full length and mutant COX-2 regulatory elements, gel shift assays, in vitro and in vivo promoter footprinting to determine the role of NF-kappaB/cRel, cEBP/NF-IL6, CREB/ATF, and other transcription factors in the induction and inhibition of COX-2 expression in ISEMF. Key findings from studies with 18Co will be confirmed in primary cultures of ISEMF from normal and various disease states. Using immunohistocytochemistry and in situ hybridization techniques we will identify the cellular sites of COX-2 gene expression in normal and diseased tissue and thus shed light on the role of ISEMF in gastrointestinal disease. These studies should define the processes which mediate signalling between intestinal subepithelial myofibroblasts and other immune and nonimmune cells, and how these processes are disrupted in pathological states such as IBD, fibrotic disorders, and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CUEING PATIENT-CLINICAN COLLABORATION TO IMPROVE ASTHMA Principal Investigator & Institution: Janson, Susan L.; Community Health Systems; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2004; Project Start 09-DEC-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Asthma is a chronic, potentially life-threatening disease that affects 17 million people in the United States. Millions of lost work days from productive activity and thousands of hospitalizations annually are caused by asthma. Despite the high prevalence, asthma is a chronic disease that can be controlled. Corticosteroids are the most effective agents for the long-term treatment of persistent asthma, and administration by inhalation minimizes the potential for systemic side effects. Despite convincing evidence of the benefits of inhaled corticosteroids (ICS), both patients and clinicians seem reluctant to use them regularly. Many patients who are prescribed ICS either never take them, or take them less frequently (e.g., once rather than twice daily), less regularly (e.g., "as needed" rather than daily), or at lower doses than prescribed. Investigators and reviewers agree that at least 50% of persons for whom medications are prescribed fail to benefit fully because of poor adherence. The reasons for nonadherence are multifaceted and not fully understood. The relationship between clinician and patient, an area where potential impact can be made, is believed
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to be the strongest predictor of medication adherence. Providing pertinent objective information about asthma related lung function should prompt therapeutic communication between the patient and clinician to improve adherence to ICS. The overall purpose of this project is to improve anti-inflammatory medication adherence and asthma outcomes by cueing therapeutic interaction between patients and their clinicians. The specific aims are to 1) improve adherence to ICS medication by cueing patient-clinician communication with feedback of objective information about airflow obstruction to reinforce medication-taking behavior; and 2) to document the impact of this cueing intervention on health care outcomes (health care utilization, pulmonary function, need for rescue courses of oral steroids, and functional impact. We hypothesize that cueing patients and their primary care clinicians about the degree of airflow obstruction will prompt interaction between them resulting in greater adherence to ICS medication over one year than will occur in a control group of similar patients who do not receive feed-back. A prospective randomized clinical trial (N=150 subjects) is proposed to test the effectiveness of this intervention. Promoting communication between adults with asthma and their clinicians in a primary care clinical setting has not yet been demonstrated. All clinicians within three general medicine practices and their individual panels of adult patients with moderate to severe asthma will be enrolled and randomized together to either the intervention or usual care. Feedback of interpreted peak flow graphs in relation to current therapy will prompt therapeutic communication. The intent is to cue and support the therapeutic relationship between clinician and patient rather than to directly intervene. The power of cueing communication lies in the ensuing therapeutic dialogue. Improvement of adherence to ICS among people with moderate or severe asthma has been shown to decrease morbidity of asthma and improve health outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEHYDROEPIANDROSTERONE THERAPY IN ACUTE ASTHMA Principal Investigator & Institution: Mcfadden, Edward R.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This project is directed toward testing the hypothesis that Dehydroepiandrosterone Sulfate (DHEAS, PB005) administered as a sterile, nonpyrogenic, lyophilized, single-dose intravenous infusion in a dose escalation fashion is safe and efficacious as an adjunct treatment to the standard therapy regimen of patients presenting to an Emergency Room with acute exacerbations of asthma. The specific aim is to determine the benefits of adding PB005 to the standard therapy regimen. This study will be conducted in a dose-escalation fashion, with the primary purpose of establishing the safety of administering PB005 versus placebo in this patient population. Patients presenting to an Emergency Room with an acute exacerbation of asthma (>6hrs) will be eligible for screening for this study. Patients consenting to participate will receive a single 30-minute intravenous infusion of Test Drug that will be initiated between the second and third doses of beta2-agonist therapy. The Test Drug will be administered via an intravenous infusion using standard sterile technique over a period of at least 30 minutes. Standard beta2-agonist therapy will be administered to all study patients with the first three doses given at 20-minute intervals, followed by hourly doses for four hours. Intravenous corticosteroids will be administered to all study patients, prior to the start of the Test Drug infusion. In addition, patients will be prescribed a 5-day course of oral steroids (20 mg, twice a day) when they are released from the hospital following the 24-hour safety assessment. Safety assessments will be
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performed during the Screening evaluation (12 hour period), continuing through the 24hour period after initiation of the Test Drug infusion, and at the Day 7 follow-up visit. Scheduled assessments will consist of medical history, asthma symptom evaluation, physical exams, cardiac monitoring (ECGs and Holter Monitoring), measurement of vital signs, spirometry, pulse oximetry, laboratory evaluations, and adverse experience reports. Asthma symptoms (dyspnea and wheezing) scores will be solicited from the patient at prescribed intervals. Patients will also be instructed to record asthma symptoms on a patient diary twice daily (a.m. and p.m.) during the one-week follow-up period, and will be asked to score symptoms during the Day 7 follow-up visit. Blood pressure, pulse, and respiratory rate will be recorded. Patients will be fitted with a Holter monitor from prior to initiation of the Test drug infusion through the 24 hour safety assessment. A baseline 12-lead ECG will be performed prior to the start of the Test Drug infusion at 30-45 minutes after completion of the Test Drug infusion, and at the 12-hour evaluation, just prior to patients release from the hospital. Serial spirometry will performed to assess study eligibility, safety, and drug efficacy. Oxygen saturation (O2 sat.) levels will be continuously monitored via pulse oximetry from the initial presentation to the Emergency Room until 12 hours after initiation of the Test Drug infusion. Bloom samples (15mL) for hematology and chemistry, and urine samples for urinalysis will be obtained upon presentation to the Emergency Room, at the 12-hour safety assessment, and during the Day 7 follow-up safety assessment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOSE OF INHALED CORTICOSTEROIDS W/ EQUISYSTEMIC EFFECTS (DICE) Principal Investigator & Institution: Boushey, Homer A.; Professor of Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DRUG THERAPY FOR PREVENTING COPD EXACERBATIONS Principal Investigator & Institution: Niewoehner, Dennis E.; Minnesota Veterans Reserach Inst 1 Veterans Dr Minneapolis, Mn 55417 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a rapidly growing global health problem and in the United States is now the fourth commonest cause of death. Symptomatic treatment for this disease is only modestly effective. Oxygen for hypoxemic patients and cigarette smoking cessation are the only known interventions that alter the natural history of the disease. Patients with established COPD frequently develop exacerbations, clinical episodes that are characterized by cough, sputum, and worsening dypsnea and caused mostly by infections. Exacerbations are very morbid and extraordinarily costly events that also accelerate deterioration in lung function. Hospitalization for COPD accounts for about two thirds of all health care expenditures for this disease. Antibiotics and systemic corticoteroids, common treatments for severe COPD exacerbations, are only marginally effective and their widespread use may be harmful to the patient and to society at large. Reducing the frequency of severe COPD exacerbations is very important, because even small reductions would confer large human and economic benefits. Described in this application is a proposal for two separate randomized clinical trials to determine
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whether low-dose theophylline or inhaled corticosteroids will reduce the frequency of severe COPD exacerbations. Once widely prescribed, theophylline has fallen into disfavor as a COPD treatment, partly due to safety issues. However, recent studies indicate that theophylline may prevent severe COPD exacerbations and that antiinflammatory activity is retained at lower and safer doses. Recent trials suggest that inhaled corticosteroids may also prevent severe COPD exacerbations, but these findings have yet to be fully confirmed. Each of the two proposed trials will randomize about 700 patients with moderate-to-severe COPD (FEV1 < 60% predicted) in equal numbers to active drug (low-dose theophylline or inhaled corticosteroids) or placebo for a one-year period. The primary outcome variable is the first occurrence of a severe COPD exacerbation (defined as an unscheduled clinic or urgent care visit requiring systemic corticosteroid therapy or hospitalization) or death from any cause. Secondary outcomes include spirometry, several measures of health care utilization, respiratory medication use, and safety. Both trials are designed with 80% power to show a 30% reduction in severe exacerbations at a significance level of 0.05. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF CHINESE HERBAL MEDICINES ON ALLERGIC ASTHMA Principal Investigator & Institution: Li, Xiu-Min; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 30-NOV-2003 Summary: (provided by applicant): Allergic asthma is a major public health problem, and the morbidity and motility of asthma have increased in the last two decades, particularly in children. The need for safe and effective asthma treatment is greater than ever. Although millions of asthma patients in the US are currently using "herbal therapies," there is little information regarding the efficacy, safety or mechanism[s] of action of herbal anti-asthma formulas. It has been shown that allergic asthma is associated with elevation of serum IgE, airway inflammation and airway hyperresponsiveness (AHR) in both asthmatic patients and animal models. Th 2-type cytokines such as IL-4, IL-5 and IL-13 play a central role in the pathogenesis of allergic asthma. To investigate the effect of herbal interventions for asthma therapy, we evaluated effects of a Chinese herbal formula, MSSM-002, on allergic airway responses using a well-characterized murine model of asthma. MSSM-002, developed in our laboratory, is based on Ja Wai San Zi Tang, used in the China-Japan Friendship Hospital in Beijing, to treat asthma and bronchitis in children. We found that MSSM-002 treatment reduced late-phase AHR, eosinophilic inflammation, mucus production, and IgE and Th2 cytokine production. Suppression of late-phase AHR by MSSM-002 was comparable to that of the potent corticosteroid, dexamethasone, and significantly greater than three commercially available Ma-Huang-containing herbal products. These preliminary results suggest that MSSM-002 has potential as an effective and safe treatment for human asthma. The objective of this project is to further investigate the therapeutic and immunoregulatory mechanisms underlying these effects. We will evaluate whether MSSM-002 can reverse maximally severe AHR, and exert a long-term as well as an acute effect on AHR. We will rigorously control the quality of herbs and consistency of the herbal formula using reproducible analytic methods such as HPLC and TLC, and further assess any possible toxicity utilizing histological and biochemical analyses. Based on our preliminary results, we hypothesize that, in contrast to the generalized immunosuppression produced by corticosteroids, MSSM-002 has specific immunomodulatory effects down-regulating the Th2 response and/or up-regulating the
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Thl response, which may underlie the observed reduction of AHR and inflammation by MSSM-002. We will further investigate the effects of MSSM-002 on in vivo and in vitro T cell cytokine production. We further hypothesize that MSSM-002 may exert beneficial regulatory effect on co-stimulatory molecules such as B7-1/B7-2 by antigen-presenting cells, which may be the upstream mechanisms of MSSM-002 regulating T cell responses. To move our study one step closer to human studies, we also plan to test the in vitro effects of MSSM-002 on human T cell responses. Accomplishing these goals should provide an experimental basis for applying Chinese herbal medicines to the treatment of allergic asthma, and for understanding immunoregulatory mechanisms underlying their effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFICACY OF LIPOSOMAL BUDESONIDE IN EXPERIMENTAL ASTHMA Principal Investigator & Institution: Konduri, Kameswari S.; Vgsk, Llc 12605 W North Ave, Pmb 299 Brookfield, Wi 53005 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 30-SEP-2004 Summary: (provided by applicant): Asthma is the most common chronic illness in childhood and affects 5 to 10% of the population. The disease is characterized by acute bronchoconstriction, chronic inflammation, and airway remodeling which may lead to progressive, irreversible lung damage. Current asthma therapy is directed at reducing the lung inflammation with the use of anti-inflammatory drugs, such as inhaled corticosteroids. If administered early in the course of the disease, they may prevent progression of the disease. However, current treatment regimens are limited by toxicity and non-compliance by the patients. Compliance is critical in interrupting the chronic inflammation and subsequent progression of asthma. Problems with compliance lead to increased hospitalizations and risk of sudden death. We propose to investigate the hypothesis that when budesonide, a frequently prescribed inhaled steroid, is encapsulated into sterically-stabilized "stealth" liposomes, it prevents inflammation of asthma in lower doses given at less frequent intervals compared to conventional daily steroid therapy. The hypothesis will be tested in a mouse model of asthma. Initial studies will define the optimal doses and frequency of dosing intervals to decrease lung inflammation, airway responsiveness to methacholine challenge, as well as toxicity of frequent dosing of the drug-liposome complex. Studies will also be performed to evaluate the stability of the drug-liposome complex. Liposomes, which are lipid bi-layer vesicles will be sterically stabilized with polyethylene glycol to encapsulate the steroid. Then the drug-encapsulated liposome will be tested in the asthma model. Asthma model will be produced in C57BI/6 mice using ovalbumin (OVA) sensitization. Experiments will be conducted on day 25, after sensitization is completed (baseline). The sensitized animals will receive aerosolized: 1) budesonide encapsulated in stealth liposomes weekly; 2) budesonide (without liposomes) either daily or weekly; 3) empty stealth liposomes (without drug) weekly. All treatment groups will be compared to 1) untreated sensitized 2) unsensitized normal mice. Histopathological examination of the lung tissues and serial measurements of eosinophil-peroxidase activity, peripheral blood eosinophil counts, and total serum IgE levels will be obtained weekly. Airway responsiveness to methacholine challenge on spontaneously breathing, intubated conscious mice will be obtained every two weeks, for sixteen weeks. Levels of budesonide will also be evaluated in bronchioalveolar lavage fluid, blood, and urine from treated animals using high performance liquid chromatography. This will be the
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first study, aimed at developing a slow release drug delivery system for inhaled steroids using stealth liposomes, with a potential to reduce toxicity and improve compliance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EISOSANOID IMBALANCE IN FIBROTIC LUNG DISEASE Principal Investigator & Institution: Peters-Golden, Marc L.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 26-DEC-2001; Project End 30-NOV-2006 Summary: (Applicant's Abstract) A growing body of evidence indicates that elcosanoid metabolites of arachidonic acid modulate the inflammatory, immune, and mesenchymal components contributing to pulmonary fibrosis. However, leukotrienes (LTs) promote all of these processes while prostaglandin E-, (PGE2) generally suppresses them. Of note, our laboratory has identified two separate abnormalities in eicosanoid synthesis in the lungs of patients with the fibrotic disease, idiopathic pulmonary fibrosis: namely, overproduction of LTs and underproduction of PGE2- Moreover, additional recent studies indicate that a similar eicosanoid imbalance characterizes animal models of pulmonary fibrosis, and that modulation of this imbalance by genetic or pharmacologic means attenuates fibrogenesis. The hypothesis of this proposal is that this pro-fibrotic imbalance of eicosanoid generation is centrally important in the pathogenesis and prognosis of pulmonary fibrosis. Furthermore, we hypothesize that this eicosanoid imbalance is exacerbated by treatment with corticosteroids, contributing to the disappointing clinical response of fibrotic lung diseases to these agents. The aims of the current proposal are to extend our understanding of the cellular and enzymatic mechanisms underlying this imbalance, its amenability to pharmacologic and/or genetic modulation, and the cytokines and (growth factors regulated by eicosanoids which influence the evolution of fibrotic lung disease. This will be accomplished by studying lung tissue and cells (macrophages and fibroblasts) from mice with bleomycin induced pulmonary fibrosis and from patients with pulmonary fibrosis. In the clinical studies proposed, eicosanoid abnormalities will be correlated with clinical severity, histologic classification, and course of disease. In addition, we will determine the effects of three treatment regimens for pulmonary fibrosis (prednisone, azathioprine plus prednisone, or the LT synthesis inhibitor zileuton) on eicosanoid synthesis, pathobiological mechanisms, and clinical outcomes. The proposed studies will critically evaluate a new pathophysiologic paradigm with important implications for therapy of this devastating group of fibrotic lung diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENDOTOXIN AND BRONCHIAL INFLAMMATION IN ASTHMA Principal Investigator & Institution: Peden, David B.; Professor of Pediatrics and Center Direc; Pediatrics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2005 Summary: (provided by applicant): In earlier studies, we have observed that allergen inflammation, induced either by allergen challenge or by natural exposure to aeroallergens during pollination seasons, enhances neutrophil influx to airway mucosal tissues following endotoxin challenge. We have also found that pre-challenge expression of CD14 on airway macrophages correlates strongly with neutrophil influx following endotoxin challenge and with baseline levels of eosinophils in the airway, and the treatment with inhaled corticosteroids decreases baseline eosinophil and macrophage
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CD14 expression and blunts response to endotoxin. We have also observed that repeated challenge with endotoxin induces tolerance to endotoxin, a phenomenon that, in animals, is reversed by GM-CSF, a product of TH2 inflammation. These findings support the hypothesis that allergic inflammation enhances response to endotoxin. Our proposal to continue these studies focuses on in vivo studies in human volunteers to examine the effect of allergen-induced inflammation on airway macrophage expression of molecules important in mediating endotoxin responsiveness and the effect of allergen challenge on bronchial response to inhaled endotoxin. We will also focus on development of tolerance to endotoxin in the bronchial airway, and assessment of CD14, TLR4, IL-1 receptor associated kinase, I?B and other mediators or modulators of endotoxin signal transduction in airway macrophages from persons undergoing a tolerance-inducing endotoxin challenge. We will also employ nasal challenge and in vitro studies of monocytic cells to examine the effect of GM-CSF and other candidate cytokines produced by IgE-mediated inflammation on in vivo and in vitro response to LPS Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCING PEDIATRIC ASTHMA MANAGEMENT Principal Investigator & Institution: Cabana, Michael D.; Assistant Professor of Pediatrics; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by the applicant): The National Heart, Lung, and Blood Institute (NHLBI) Guidelines for the Diagnosis and Management of Asthma recommend that practitioners prescribe daily anti-inflammatory medications for children with persistent asthma. The guidelines specifically describe corticosteroids as "the most potent and consistently effective long-term control medication for asthma". However, despite the publication of the NHLBI guidelines, there has been limited effect on physician prescription of daily-inhaled corticosteroids (DCS) for these patients. There are limited studies evaluating methods to improve physician adherence to the NHLBI asthma guidelines. Using a randomized controlled trial design, we will evaluate the effects of barrier assessment and a multi-faceted intervention to improve pediatrician prescription of DCS to children with persistent asthma. We have developed a theoretical framework that describes barriers that physicians must overcome before adhering to a guideline. In the first phase of the proposed project, at 22 primary care pediatric practices, using this framework, we will systematically assess barriers prescribing DCS to children with persistent asthma. In the second phase of the project, we will evaluate if a multi-faceted intervention featuring interactive physician seminars, based on the barrier assessment in the first phase can promote physician prescription of DCS to pediatric patients with persistent asthma. Over a three-year period, we will measure changes in pediatrician knowledge, attitudes and practice of DCS prescription using chart audits, parent telephone survey, and physician survey. It is expected that when compared to pediatricians in the control group, pediatricians who participate in the barrier assessment and multi-faceted educational seminars will have improved knowledge and attitudes towards the use of DCS, as well as increased prescription of DCS for their patients with persistent asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENERAL CLINICAL RESEARCH CENTER Principal Investigator & Institution: Roth, Paul B.; Clinical Research Center; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-MAY-1976; Project End 30-NOV-2002 Summary: This is the 21st year of the continuation grant of the General Clinical Research Center at the University of New Mexico School of Medicine with its unique multi-ethnic patient population. Major areas of investigation are: Neuroendocrinology/Psychiatry: Examination of the hypophyseal/pituitary/adrenal axis in neuropsychiatric and metabolically altered states, depression, and post traumatic stress. Endocrinology: Molecular biology of aldose-reductase modulation of the polyol pathway in patients with diabetic complications, including status of oxidative stress on the development of diabetic complications. Metabolism: Determination of brain glucose utilization during normal and hypoglycemic states and its relationship to energy expenditure in man. Ketone kinetic investigation in diabetes in relation to insulin regulation and counterregulatory hormone exposure. Investigation of glucose regulation in the elderly. Bioengineering: Development and evaluation of algorithms for the non- invasive infrared glucose sensor. Development and evaluation of the fetal monitor by infra-red technology for pH, p02, and pC02. Nutrition: Longitudinal studies of the nutritional status of healthy elderly persons, studies of their intake, absorption. Neonatology: Role of Human Epidermal Growth Factor on pulmonary maturation in the perinatal period and regulation by corticosteroids; investigations of red blood cell and leukocyte kinetics and molecular regulation in the neonate during expansion with growth factors. Neurology: Role of matrix metalloproteinases in maintenance of the blood- brain barrier in injury, stroke and multiple sclerosis. Infectious Disease: Investigation of emerging pathogens, molecular biology of Hantavirus, Herpes Simplex Virus, and Human Papillomavirus. Pulmonary: Pathophysiology of functional pulmonary immunity in the human being. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENOME SEQUENCING OF ASPERGILLUS FUMIGATUS Principal Investigator & Institution: Denning, David W.; Victoria University of Manchester Oxford Rd Manchester, Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Aspergillus fumigatus is the most common cause of life-threatening mold infection (aspergillosis). Its spores are found in the air everywhere and are therefore unavoidable. It particularly affects those with damaged immune systems, especially transplant recipients, those on corticosteroids and leukemia patients. Autopsy studies have shown a prevalence of invasive aspergillosis of 4% in University hospitals, a 1400% increase on one decade earlier. This application is for the US contribution to the genome sequencing of A. fumigatus through an international initiative led by the applicant. The international contributors are the US (Manchester/TIGR), the UK (Sanger), France (Genoscope), Spain and Japan. The genome is estimated to be 30Mb in size containing about 8000 genes. This proposal is to sequence and annotate 12Mb, about 40% of the genome. The project has been initiated at the Sanger with the construction and characterization of a 100Kb BAC library. This library will serve as the resource for the assignment of genomic regions to sequencing centres. Data release will be at least monthly. The seguencing and initial annotation will be completed within 3 years. The sequencing and informatics technology to be developed with this project at TIGR will extend whole genome sequencing by reducing costs and improving quality for small
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eucaryotic genomes. Additionally this project will serve as a model of international collaboration for medium-sized genomes. Progress of the project and sequence data will be brought together on the Aspergillus Website (www.aspergillus.man.ac.uk). The key benefit from this project will be a genetic resource, available for all time, to understand Aspergillus, including basic biological systems, virulence characteristics, key antigens for allergenicity and immune protection, mechanisms of drug resistance, new antifungal drug targets and secondary metabolite production. This unique resource will bring in the larger Aspergillus research community to translate much of what is known of other Aspergillus species (nidulans, flavus/parasiticus, niger) to develop tools for managing human disease and to develop a functional understanding of the entire physiology and metabolism of the organism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCAGON AND HEPATIC GENE EXPRESSION IN SURGICAL SEPSIS Principal Investigator & Institution: Harbrecht, Brian G.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 30-NOV-2005 Summary: (Verbatim from the applicant's abstract) The body's response to injury and surgical stress involves the coordinated elaboration of a number of pro-inflammatory and anti-inflammatory mediators which function to prevent the spread of invading organisms, minimize tissue injury, repair damaged tissues, and restore homeostasis and vital organ function. Among the earliest mediators produced in response to injury and infection are catecholamines, corticosteroids, and glucagon. The mechanisms by which glucagon regulates glucose homeostasis have been well characterized, while the ability of glucagon to alter other metabolic pathways has not been extensively studied. The expression of nitric oxide synthase in hepatocytes is important in the response of the liver to infection because NO from the inducible nitric oxide synthase (iNOS) contributes to sepsis-induced hepatic injury and hepatic dysfunction. Our preliminary data demonstrate that glucagon inhibits hepatocyte nitric oxide (NO) synthesis by inhibiting the expression of iNOS in response to pro-inflammatory stimuli in both in vitro and in vivo models of sepsis. The reduction in iNOS expression with glucagon is associated with decreased LPS-mediated hepatic injury and decreased LPS-mediated hepatic dysfunction. In this proposal, we will identify the mechanisms responsible for the regulation of this critical hepatocyte pathway by glucagon. We will identify the mechanisms involved in the transcriptional regulation of iNOS by glucagon (AIM D, the regulation by glucagon of post-transcriptional effects on iNOS expression (AIM II), and the second messenger signal transduction systems responsible for these events (AIM III). By defining the mechanisms involved in the regulation of iNOS expression by glucagon, we will enhance our understanding of the cellular events that constitute the body's response to injury, stress, and infection. These insights will contribute to uncovering the basic cellular mechanisms involved in multiple organ dysfunction and may lead to potential therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GOBLET CELL DYSFUNCTION IN ASTHMA Principal Investigator & Institution: Fahy, John V.; Associate Professor of Medicine; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747
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Timing: Fiscal Year 2002; Project Start 07-DEC-1998; Project End 30-NOV-2003 Summary: The mechanisms of mucus hypersecretion in asthma are poorly understood, even though sputum production is a prominent symptom of asthma exacerbations, and mucus plugging of the airways is prominent in the airways of patients who die from acute severe asthma. Although goblet cell hyperplasia is a pathologic feature of animal models of asthma, and allergen-induced goblet cell degranulation causes airway obstruction in sensitized animals, the role of the goblet cell in the pathogenesis of mucus hypersecretion and airway obstruction in human asthma is not clear. We hypothesize that the phenotype of the airway epithelium in mild and moderate asthma is characterized by goblet cell hypertrophy and hyperplasia, placing these patients at risk for acute episodes of airway obstruction secondary to an exaggerated goblet cell degranulation response to stimuli such as allergen and viruses. We further hypothesize that overexpression of mucin genes in airway goblet cells is one mechanism for goblet cell hypertrophy and hyperplasia. We propose to test our hypotheses using rigorous methods of quantitative morphometry, in situ hybridization, and RT-PCR to quantify goblet cell size, goblet cell degranulation, and goblet cell expression of mucin genes in endobronchial biopsies obtained during bronchoscopy from healthy and asthmatic subjects. In addition, because the effects of current asthma treatments on goblet cells are unknown, and because there is a need for studies of specific treatments of goblet cell hyperplasia, we propose to begin to explore the treatment of goblet cell abnormalities in human asthma by examining the effects of inhaled corticosteroids on goblet cell hypersecretion, goblet cell mucin secretion, and goblet cell mucin gene expression. Aim 1 will determine if mRNA levels for MUC-2 and MUC-5AC are higher than normal in goblet cells in the airway epithelium of asthmatic subjects. Aim 2 will determine if goblet cell degranulation occurs in asthmatic subjects following allergen challenge. Aim 3 will determine if treatment with an inhaled corticosteroid decreases mucin stores in goblet cells, mucin secreted on the airway epithelial surface, and mucin mRNA levels in endobronchial biopsies. The proposed studies address an unmet need, because few studies have been published focusing on goblet cells in human asthma. The application of the methods described here provide the opportunity to begin to understand the relationship between goblet cell hypersecretion and airway obstruction in human asthma, and may suggest strategies for improving treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HAIR FOLLICLE BULGE CELLS IN TUMORIGENESIS AND ALOPECIA Principal Investigator & Institution: Cotsarelis, George; Assistant Professor; Dermatology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Verbatim) The long-term goals of this project are to better understand epithelial stem cell biology. Epithelial stem cells are responsible for the continual regeneration and homeostasis of all self-renewing tissues such as the epidermis, hair follicle, and corneal epithelium. We originally identified epithelial stem cells in the limbal epithelium of the cornea, and in the bulge region of the outer root sheath of the hair follicle. Recently, we demonstrated that cytokeratin 15 (K15) is selectively expressed by bulge cells, and our preliminary results show that K15 is also expressed in the limbal epithelium of the cornea. Now, we have isolated the K15 promoter, and we plan to use this as a tool to study the hypothesis that bulge cells play a major role in hair follicle cycling, alopecia, wound healing, and carcinogenesis. Specifically, we plan to: 1. characterize K15 promoter activity during development, throughout the hair follicle
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cycle and in response to hyperproliferative stimuli. We will test the hypothesis that K15 is preferentially expressed in other sites enriched in epithelial stem cells by examining its expression in corneal epithelium as well. Our primary goal is to develop a transgenic system that can be modulated by exogenous agents (e.g., retinoids, phorbol esters, corticosteroids) so that we can study tissue compartments rich in epithelial stem cells. 2. determine whether sonic hedgehog (shh) and activated beta-catenin, known to cause basal cell carcinomas and hair follicle tumors, respectively, when expressed throughout the epidermal basal layer, cause similar or distinct tumors when targeted to the bulge cells by the K15 promoter in a transgenic system. 3. assess the role of the bulge cells in hair follicle cycling by analyzing the hair cycle in transgenic mice that over-express shh and activated beta-catenin. 4. ablate hair follicle bulge cells in adult transgenic mice carrying a K15 promoter/thymidine kinase suicide gene. This addresses the hypothesis that the bulge contains stem cells responsible for hair follicle cycling, epidermal renewal and sebaceous gland regeneration. We also plan to use this system as a model for studying scarring alopecias. Patients with disorders such as alopecia, basal cell carcinoma, hair follicle tumors, or chronic wounds may ultimately benefit from this research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEAT SHOCK AND STEROID RECEPTOR SIGNALING Principal Investigator & Institution: Sanchez, Edwin R.; Professor; Pharmacology and Therapeutics; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2002; Project Start 01-JAN-1992; Project End 31-MAR-2006 Summary: (provided by applicant) The glucocorticoid receptor (GR) and heat shock factor 1 (HSF1) are transcription factors that control the response of cells to corticosteroids and cell stress, respectively. Because the inactive forms of GR and HSF1 are maintained by similar, if not identical, Hsp90-based protein-folding complexes, our laboratory has investigated the nature of cross-talk between these otherwise independent signal pathways. We have documented a dramatic and non-reciprocal regulation between GR and HSF1 in cells exposed to glucocorticoid hormone and stress. Using cells stably- transfected with GR- and HSF1 -responsive promoters, we find that heat shock and other forms of stress greatly enhance hormone-induced GR-mediated gene expression, while glucocorticoid hormones suppress the activity of HSF-1. We now have evidence that stress potentiation of GR requires intrinsic HSF1 activity, and that glucocorticoid hormone inhibition of HSF1 requires genomic action on the part of GR. Most intriguing is our latest finding that a protein-protein interaction between GR and HSF1 can occur in cells exposed to hormone and stress. As this interaction appears to occur in the nuclear compartment when the activated forms of GR and HSF1 are present, we now propose a model for mutual regulation in which a direct (or indirect) binding of GR and HSF1 at their respective promoters can cause either the heat shock potentiation of GR, or the GR repression of HSF1, or both. In Specific Aim 1 of this proposal, we will test this model in a variety of ways, most notably, through use of the chromatin immunoprecipitation assay - an assay used to detect proteins and protein complexes localized to promoters in vivo. In Specific Aim 2, we will explore additional mechanisms to explain stress potentiation of GR transactivity, including stress-induced alterations to the GR heterocomplex and to co-regulator recruitment at a GR-regulated promoter. In addition, we will further characterize the role of HSF1 activity in stress potentiation of the receptor through use of constitutively-active and dominant-negative forms of HSF1. In Specific Aim 3, we investigate GR repression of HSF1 through use of
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GR mutants expressing variable transactivation and transrepression properties, by mapping the presence of putative GR-binding sites on an HSF1-responsive promoter, and by assessing alterations to various properties of HSF1 activity at its promoter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HGF IN LIVER DEVELOPMENT,REGENERATION AND NEOPLASIA Principal Investigator & Institution: Michalopoulos, George K.; Professor and Chairman; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 15-JUL-1983; Project End 31-DEC-2007 Summary: (provided by applicant) The main goal of the proposal is to understand the role of Hepatocyte Growth Factor (HGF), its receptor (cMet) and the hepatic biomatrix as determinants of hepatic growth, regeneration, tissue differentiation and neoplasia. Converging studies from our lab and others have identified HGF and matrix as key parameters in all these processes. Based on previous work, we have identified different roles and sources for HGF for the first 3 hours after partial hepatectomy (PHx), primarily from pre-existing matrix stores, and following 3 hours after PHx, primarily from newly synthesized HGF. Animal (rat and mouse) models, including conditional homozygous deletion of hepatic HGF gene, are to be employed to study the functions of HGF in liver regeneration. The same models will also be employed to understand the role of hepatic HGF during development of hepatic neoplasia. New HGF at 3 hours post PHx is synthesized not only in liver but also in remote sites. Since we found that norepinephrine stimulates synthesis of new HGF and also rises in the plasma after PHx, will pursue studies to explore the role of norepinephrine as the messenger for HGF synthesis throughout the body after PHx. In studies from the previous period we found that beta-catenin is subjected to tyrosine phosphorylation by cMet. We also now have evidence that beta-catenin is a key regulator of the early stages after PHx and it is subjected to tyrosine phosphorylation by cMet. Studies are proposed to understand the interaction between cMet and beta-catenin, including transgenic mice in which betacatenin is expressed under the albumin promoter. Since beta-catenin mutations are important in liver cancer in humans, the proposed studies will provide information on the function of beta-catenin and its interaction with cMet as regulators of hepatic neoplasia. We have designed organoid cultures in which HGF, EGF and corticosteroids interact in a complex medium (HGM) to allow growth of hepatocytes and nonparenchymal cells, so that they form reproducible and recognizable structures of hepatic histology in a completely defined environment. We have found that corticosteroids and HGF are essential for hepatocyte maturation. HGF and EGF are essential for formation of the complex connective tissue and the fully mature biliary epithelium seen in these cultures. This system allows development biology studies impossible in mouse genetic systems. Proposed studies aim to use this "in vitro embryology" system and provide answers on the role of HGF and matrix in hepatic tissue development and differentiation. Finally, we have succeeded in isolating relatively pure material on a key transcription factor (HNFx, for the purposes of the grant) that appears to regulate matrix- and HGF-induced hepatocyte differentiation in culture. Preliminary studies suggest that HNFx is related or identical to Ear2 transcription factor. Studies are described to determine the nature of HNFx and its regulation by growth factors and matrix during hepatocyte differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THERAPY
HIPPOCAMPAL
FUNCTION
DURING
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Principal Investigator & Institution: Brown, E Sherwood.; Assistant Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract) This Mentored Clinical Scientist Development Award (MCSDA) application defines a training program to facilitate the development of the Pl as an independent researcher in the area of mood disorders. The educational activities outlined will enable the Pl to explore the biological basis of corticosteroid effects on brain function. During the course of this award, Dr. A. John Rush will serve as the PI's mentor. Additional experts providing instruction and training include: Drs. Frederick Petty (clinical trials), Bruce S. McEwen (glucocorticoids and the hippocampus), and Alan Frol and C. Munro Cullum (cognitive neuroscience). Measurement of hippocampal volumes from MRI scans will be performed by Dr. John Csernansky's group at Washington University. The training entails increasing the PI's knowledge of neuropsychological testing and clinical research methodology. The Pl plans to use cognitive testing to develop a paradigm in humans for exploring pharmacologic interventions which may prevent or reverse hippocampal changes associated with corticosteroids. In order to achieve the stated training goals, the Pl has developed a program that includes didactic courses, tutorials, and a research project. The proposed project will afford a hands-on experience, reinforcing the information and techniques learned through mentoring and classroom environments. The Pl will first examine memory, mood, and hippocampal volume in asthma and rheumatoid arthritis patients receiving chronic oral prescription corticosteroid therapy, a population the Pl has actively researched for over three years. In animals, agents which inhibit the release of glutamate appear to prevent and reverse hippocampal damage secondary to corticosteroids. Thus, the first experiment in the training plan will be followed by a clinical trial of the glutamate release inhibitor, lamotrigine, to determine if neurocognitive changes associated with corticosteroids can be reversed in humans. Through this award, the Pl will extend his previous research experience by adding new skills and knowledge which will be used for investigations at the interface of neuroscience and clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNDROME
IMMUNOTHERAPY
OF
LOW
RISK
MYELODYSPLASTIC
Principal Investigator & Institution: Molldrem, Jeffrey J.; Chief, Section of Transplant Immunology; Blood & Marrow Transplantation; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Provided by applicant): Myelodysplastic syndrome (MDS) is a heterogeneous group of progressive, irreversible, hematopoietic stem cell disorders characterized by progressive cytopenia and for which there are no effective therapies. Experimental and clinical evidence indicates that lymphocytes from patients with MDS exert an inhibitory effect on autologous hematopoietic colony growth, and that this contributes to cytopenia. Immunosuppressive treatments that decrease the number of lymphocytes or suppress their function such as corticosteroids, cyclosporine, and antithymocyte globulin (ATG) have been shown to reverse that cytopenia, and in some cases to reduce the number of blasts in the marrow. How these lymphocytes recognize
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their target antigens and inhibit hematopoietic precursors is unknown. Identification of relevant hematopoietic target antigens, however, might lead to useful therapies for MDS, and would provide insight into other bone marrow failure states such as aplastic anemia where T lymphocytes are also thought to play a key role in the development of pancytopenia. As a strategy to search for those target antigens, we hypothesize that in myelodysplastic syndrome, lymphocyte inhibition of hematopoietic progenitors is mediated by clonal or oligoclonal activated T lymphocytes through MHC-restricted antigen recognition. The long-term goal of this project is to investigate whether clonal T cells associated with inhibition of marrow progenitors can be isolated from MDS patients and then used to further identify relevant target antigens. These clonal T cells could then be more specifically targeted in the treatment of MDS patients and identification of T cell target cells/antigens could help determine the proportional contribution of lymphocytes to the development of cytopenia in MDS. We have shown that patients with MDS who respond to ATG treatment have activated CD8+ lymphocytes that inhibit colony forming unit-granulocyte macrophage (CFU-GM) in a MHC class I-restricted manner. Dominant clonal and oligoclonal lymphocyte populations that are present in peripheral blood and bone marrow in some MDS patients are later replaced by a normal polyclonal distribution, which coincides with reestablishment of effective hematopoiesis after ATG treatment. The proposed studies will isolate and characterize clonal T cells from MDS patients, determine how these T cell clones suppress hematopoiesis, whether T cell-mediated inhibition of hematopoiesis is directed against dysplastic or normal progenitors, and whether additional T-celldirected immunosuppressive agents added to ATG treatment can enhance recovery from cytopenia in a randomized clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO IMAGING OF LEUKOCYTE-ENDOTHELIAL DYNAMICS Principal Investigator & Institution: Mathers, William D.; Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The process of leukocyte migration across the vascular endothelial barrier is fundamental to the process of inflammation and the response to infection. We will quantitate the effect of various medications such as topical corticosteroids, oral nonsteroidal anti-inflammatory drugs, and mast cell stabilizers in several of these processes. We have applied intravital microscopy in animal systems to visualize, quantitate and analyze this process. Recent advances in confocal microscopy have allowed a European group to quantitate leukocyte endothelial rolling and sticking in the microvasculature of the human eye. Combining our clinical expertise in confocal microscopy and our experience analyzing leukocyte vascular interactions, we propose to utilize in vivo confocal technology to quantitate leukocyte rolling and arrest in 4 different human vascular beds: the limbus, conjuctiva, episclera, and sclera. With these three specific aims: Aim one, we propose to image rolling and sticking of leukocytes in four different normal ocular vascular beds: the conjunctiva, limbus, episclera, and sclera. Aim two, we will compare leukocyte-endothelial dynamics in specific vascular beds in seven disease states: a) allergic seasonal conjunctivitis, b) Sjogren's syndrome and dry eye, c) blepharitis, d) graft versus host disease (GVHD), e) episcleritis, f) scleritis, and g) anterior uveitis. Aim three, we will determine the effect of medications including topical prednisolone acetate, a mast cell stabilizer (optipranolol), or an oral nonsteroidal antiinflammatory drug (indomethacin) on endothelial-leukocyte dynamics in diseases for which each is frequently prescribed. Our studies will directly clarify the pathogenesis of
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several troublesome and rarely studied ocular disease processes. These studies will elucidate the mechanism by which medications alter these processes. Most importantly these studies will quantitate a fundamental human biological process in microvascular beds that have not previously been imaged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INCREASING ADHERENCE IN INNER-CITY ADULTS WITH ASTHMA Principal Investigator & Institution: Krishnan, Jerry A.; Instructor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Asthma is common chronic disease characterized by episodic respiratory symptoms. While there are effective therapies, inadequate symptom control remains an important problem, particularly for low-income adults living in the inner-city. As in other chronic diseases, adequate self-management skills are necessary to reduce the burden from asthma. However, non-adherence to effective therapy has been repeatedly identified in patients with inadequate symptom control. Strategies focused on improving knowledge alone have not had consistent clinical benefits in patients with asthma, strongly suggesting that education alone does not modify patients? patterns of care. Patients? attitudes and beliefs about asthma and asthma care can also affect behavior. In particular, patients? self-efficacy and attitudes/beliefs regarding their ability to effectively deal with asthma symptoms may be critical for appropriate levels of adherence to effective therapy. However, recent evidence suggests that asthma self-efficacy and attitudes/beliefs about asthma control may be inadequate in high-risk inner-city adults. Objective adherence monitoring and patient feedback can identify specific adherence difficulties and reinforce effective patterns of medication use, and may thus improve self-efficacy and attitudes/beliefs about asthma control. Based on this construct, we hypothesize that objective medication monitoring with patient feedback will improve adherence to inhaled corticosteroids (ICS), the most widely used mediation for asthma control. The primary objective of this proposal is to combined asthma education with objective adherence monitoring and patient feedback as a novel integrated approach to improve adherence to ICS in innercity adults with poor asthma control. To this end, we propose two related studies in this population: a) a prospective cohort study to objectively describe baseline patterns of adherence to ICS (Specific Aim 1), and b) a randomized intervention trial to assess the effectiveness of this novel integrated approach to improve adherence to ICS (Specific Aim 2). This body of mentored patient-oriented research will provide Dr. Krishnan new knowledge, skills, and collaborative relationships necessary to successfully apply for funding as an independent investigator during the fourth year of this award. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INFORMATIVE CLINICAL STUDIES IN ASTHMA Principal Investigator & Institution: Israel, Elliot; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Despite significant advances in the treatment of asthma, optimal clinical therapy for patients with this increasingly common and potentially debilitating disease is still in flux. The first trial we propose for the Asthma Clinical Research Network (ACRN) emerges from expert-based guidelines
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recommending that individuals with mild-moderate persistent asthma symptoms, who comprise about 50% of patients requiring chronic asthma therapy, should be treated with controller agents such as inhaled corticosteroids (ICS). However, this may lead to over-treatment of many individuals who do not require such therapy. Data from a completed ACRN trial suggest that more than 60% of patients whose symptoms were controlled with continuous ICS did not experience exacerbations when discontinuing this medication. Our retrospective analysis of this trial suggests that changes in sputum eosinophils may identify 80% of the patients who can successfully discontinue inhaled corticosteroids. If confirmed, such a tool could prevent unnecessary treatment for a large cohort of asthmatics and result in an estimated $2 billion of savings per year. It could also identify patients requiring further therapy. We propose a double blind, placebo-controlled study to test this hypothesis. Our second trial focuses on patients with more severe disease, who account for a disproportionate amount of asthma-related morbidity. For patients whose symptoms persist in spite of treatment with ICS and a long-acting -agonist, alternatives are needed to the current recommendation of treatment with higher doses of ICS. Newer agents, such as leukotriene modifiers, may be beneficial for such patients. We will examine the effect of adding a leukotriene modifier to ICS and a long-acting -agonist vs. increasing the dosage of ICS with continuation of a long-acting -agonist among patients with moderate to severe asthma. Both trials will use asthma deteriorations as the primary outcome. In the second trial, we will also examine if the response to ICS therapy is associated with haplotypic variations in the gene coding for the glucocorticoid receptor and if the response to leukotriene modifiers is associated with polymorphisms of the LTC4 synthase promoter. This latter analysis may permit us to individualize therapy and therefore maximize benefit, decrease toxicity, and decrease cost. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHALED CORTICOSTEROIDS /ADRENAL FUNCTION IN COPD PATIENTS Principal Investigator & Institution: Wise, Robert A.; Professor of Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LACTOFERRIN IN PRIMATE AND MOUSE MODELS OF ASTHMA Principal Investigator & Institution: Varadhachary, Atul Dr.; Agennix, Inc. 8 Greenway Plz, Ste 910 Houston, Tx 770460892 Timing: Fiscal Year 2004; Project Start 15-MAY-2004; Project End 31-OCT-2004 Summary: (provided by applicant): The purpose of this research is to extend work to determine the efficacy of orally administered recombinant human lactoferrin (rhLF) in an established primate model of asthma. Asthma is one of the most prevalent chronic inflammatory diseases in the United States affecting -15% of the population. Despite intensive research on asthma over the past decade the prevalence, morbidity and mortality rates continue to increase in the U.S. and the developed world. Over 1% of total healthcare costs in the U.S. are directed towards the therapy and treatment of this disease. In spite of research efforts, few new drugs have been approved for the treatment of asthma. Corticosteroids and Beta-adrenergic Agonists remain the predominant therapies but unfortunately are not effective in all patients. In addition,
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corticosteroids are associated with a number of potential adverse side effects including growth retardation in children, osteoporosis, glaucoma and cataracts. There remains, therefore a large unmet medical need for new drugs that can more effectively and safely treat this disease. During a previous study in a sheep model of asthma, inhaled lactoferrin, a naturally occurring immuno-stimulatory protein, was shown to inhibit the inflammation which characterizes asthma. New research by Agennix indicates that orally administered lactoferrin is also effective in treating asthma through a novel mechanism involving the stimulation of IL-18. I1_-18 is a potent cytokine that may serve to shift the TH2 immune response responsible for the inflammation associated with asthma. Given the robust safety profile of orally administered lactoferrin there exists a possibility that lactoferrin may represent an exciting, safe and novel new therapy for asthma. This research will seek to a.) Confirm earlier results in sheep and definitively test the efficacy of orally administered lactoferrin in a non-human primate model, b.) Determine in primates the optimal dose and regimen for using lactoferrin as a treatment for allergen-induced asthma symptoms, co) Further elucidate the potential mechanisms of action of rhLF in asthma, d.) Provide evidence supporting future clinical trials in this indication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LONGITUDINAL OPTIC NEURITIS STUDY Principal Investigator & Institution: Moke, Pamela S.; Jaeb Center for Health Research, Inc. Suite 350 Tampa, Fl 33647 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-MAR-2007 Summary: This proposal is to continue a long-term follow-up study of the cohort of patients who were entered into the Optic Neuritis Treatment Trial (ONTT) between 1988 and 1991 and have been followed as part of the Longitudinal Optic Neuritis Study (LONS) since 1992. The ONTT's primary objective was to assess the efficacy of corticosteroids in the treatment of acute optic neuritis. The LONS' primary objectives are (1) the evaluation of the long-term course of visual function after optic neuritis and (2) investigation of the relationship between optic neuritis and multiple sclerosis (MS). This application is for a continuation of the LONS to acquire additional valuable longterm follow-up information about both the visual course and the neurologic course in this unique patient cohort. The LONS provides a unique opportunity to study a cohort of well- characterized patients with optic neuritis. No other study has ever assembled and evaluated so extensively with standardized methodology such a large number of patients with optic neuritis. The importance of the treatment trial in providing a cohort of patients which could be followed longitudinally to answer many key visual and neurologic questions concerning optic neuritis was recognized from the onset of development of the ONTT protocol. This cohort of patients was assembled through considerable effort and cost. The costs involved in the current proposed five-year extension are small compared to the overall study costs. The information emanating from this study will have both therapeutic and quality of life relevance for patients with optic neuritis. For the first four years of the proposal, patient contact will be maintained through phone calls and mailings from the Data Coordinating Center. In the fifth year, the 14 LONS clinics will be recertified and each patient will be seen for an ocular examination, visual function testing, and neurologic examination by protocols currently utilized in the LONS. This visit will coincide with 15-17 years of follow up for each patient. Major manuscripts are planned for both the ophthalmic and neurologic results. More than 80% of the original cohort remains in follow up and mechanisms are in place
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to assure that this high rate will continue so as to provide valid results for the long-term study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LYSOSOMAL PHOSPHOLIPASE A2 IN LUNG DPPC METABOLISM Principal Investigator & Institution: Fisher, Aron B.; Professor and Director; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 10-DEC-2001; Project End 30-NOV-2006 Summary: This project will evaluate the properties and physiological role of a novel phospholipase A2 (aiPLA2) that was identified during the preceding period of grant support. We have isolated the protein from rat and bovine lungs, have identified full length cDNA clones for the human, rat, mouse, and bovine enzyme, and have generated a panel of antibodies. This unique PLA2 is Ca++-independent and shows maximal activity at pH4 and thus internalized alveolar DPPC and also provides substrate for the reacylation pathway of DPPC synthesis. This study will utilize native and recombinant aiPLA2 mutant aiPLA2 proteins, isolated alveolar type II cells, several cell lines, isolated rat and mouse lungs, and intact animals, to study activity and regulation of aiPLA2 and its physiological role in lung surfactant metabolism. Specific Aim 1 will investigate the regulation of aiPLA2 activity. We will utilize co-immunoprecipitation and surface plasmon resonance techniques to evaluate interactions between aiPLA2 and SP-A, which we propose is a physiological regulatory of enzyme activity. We will evaluate possible glutathiolation and phosphorylation as additional regulatory mechanisms. Specific Aim 2 will evaluate structure-function relationships for aiPLA2 activity utilizing site directed mutagenesis and fluorescence resonance energy transfer measurements to determine binding of substrate to protein and to determine the amino acid residues required for activity. Specific Aim 3 will investigate the regulation of aiPLA2 expression with emphasis on developmental expression using the timed pregnant rat and human lung samples. We will also evaluate a role for corticosteroids, cAMP, and KGF in regulation of aiPLA2 expression. Specific Aim 4 will evaluate subcellular localization of the enzyme utilizing fluorescence and electron microscopy, subcellular fractionation techniques, and analysis of subcellular targeting signals. We postulate that the protein is targeted to the lysosomal compartment for PLA2 activity. Specific Aim 5 will develop several models of under-and over-expression of aiPLA2 and evaluate the resultant effects of DPPC degradation and synthesis using isolated cells, the isolated perfused lung model, and in vivo studies. These studies will provide important insights into a novel enzyme of major importance to lung surfactant metabolism and will provide the basis for further in depth characterization of lysosomal PLA2 activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MATRIX METALLOPROTEINASES AND THE BLOOD-BRAIN BARRIER Principal Investigator & Institution: Rosenberg, Gary; Chairman & Professor; Neurology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Matrix metalloproteinases (MMPs) disrupt the blood-brain barrier (BBB) in many neuroinflammatory diseases. They are secreted as latent enzymes, which are activated by proteases and free radicals and inhibited by tissue inhibitors of metalloproteinases (TIMPs). Gelatinase A (MMP-2) and B (MMP-9)
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attack extracellular matrix around blood vessels. Cell cultures of astrocytes produce latent MMP-9 when stimulated by lipopolysaccharide (LPS), and microglia form active MMP-9. Microglia secrete stromelysin- 1 (MMP-3), which may be the activator of MMP9. Intracerebral injection of LPS induces cytokines, free radicals, and proteases that simulate the neuroinflammatory response by producing active forms of the MMPs and opening the BBB. We hypothesize that the balance between the MMPs and the TIMPs controls the permeability of the BBB, and that MMP-3 contributes to the BBB damage by activation of proMMP-9, while TIMP-3 protects the BBB by inhibiting the MMPs. To test the hypothesis, we propose to use mice lacking the MMP-3 or TIMP-3 genes. Specific Aim 1: To determine the relationship of the expression of the cytokines, MMPs, and TIMPs to the BBB damage after an intracerebral injection of LPS in mice. 3H-sucrose (m.w. 342) and 14C-dextran (m.w. 50-90 kDa) will be used for BBB permeability measurements. Expression of mRNA for TNF-alpha, IL-1beta, MMP-2, -3, and -9, and TIMP-1 and -3 will be measured by realtime rtPCR. Zymography and immunohistochemistry of the MMPs and TIMPs will be used to determine proteins and cellular localization. Specific Aims 2 and 3: To study the role of MMP-3 (aim 2) and TIMP-3 (aim 3) in BBB proteolysis by the use of MMP-3 and TIMP-3 null mice. BBB permeability will be measured with radiolabeled tracers, and the effect of gene knock out on the production and activation of the MMPs will be measured by zymography and rt-PCR. Specific Aim 4: To identify the molecular mechanisms involved in the protection of the BBB by corticosteroids, tetracycline derivatives, and synthetic MMP inhibitors. BBB disruption is a major factor in multiple sclerosis, Guillain-Barre Syndrome, meningitis, and cerebral bleeding after thrombolysis. Understanding the molecular events in the BBB disruption by MMPs will provide a rational basis for drug design, and will lead to novel treatments in many important neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MATURATION OF K TRANSPORT IN THE DISTAL NEPHRON Principal Investigator & Institution: Satlin, Lisa M.; Professor; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-JUL-2006 Summary: (provided by applicant): The magnitude of K+ secretion in the cortical collecting duct (CCD) is determined by its electrochemical gradient and the permeability of the apical membrane to K+. Two apical K+-selective channels have been identified by patch clamp analysis of the fully differentiated CCD. Whereas the secretory K+ (SK) channel, encoded by ROMK, is considered to mediate baseline K+ secretion, the role of the stretch-/Ca2+-activated maxi-K channel, closed at the resting membrane potential, remains uncertain. Two observations suggest that channels other than ROMK contribute to urinary K+ secretion. First, patients with Bartter's syndrome due to loss-of-function mutations in ROMK have modest hypokalemia and not hyperkalemia, as might be expected in the absence of functional SK channels. Second, the developmental appearance of baseline net K+ secretion in the rabbit CCD precedes that of flowstimulated K+ secretion. In fact, recent data from our lab suggests that flow-dependent K+ secretion is mediated by the maxi-K channel. We hypothesize that the differential expression of alternative spliced transcripts of the maxi-K channel, encoded by slo, that vary in Ca2+ and voltage sensitivity, or in coassembly with regulatory beta subunits, provides a mechanism for modulating flow-dependent K+ secretion in the CCD during normal renal development and the adaptation to disease. To test this, we propose to: (1) define the molecular identity of the renal maxi-K channel subunit isoforms, their functional characteristics, distribution and abundance in the maturing mammalian
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kidney, and (2) explore the mechanisms by which epigenetic factors, including dietary K+ intake and plasma K+ levels, circulating levels of adrenal corticosteroids and vasopressin regulate maxi-K channel expression and activity. A complementary approach of molecular and functional (in vitro microperfusion and patch clamp analysis) studies is planned. The results of this investigation have broad implications not only in terms of our understanding of the pathophysiology of disease (Bartter's), but also the ontogeny of renal tubular function. Additionally, this study sets the stage for future exploration of the role of biomechanical forces (e.g. flow), via activation of appropriate signal transduction cascades (e.g., Ca2+-associated), in regulation of gene expression as is necessary for normal tubular differentiation and adaptation to disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ETHANOL INDUCED IMPAIRMENTS IN IMMUNITY Principal Investigator & Institution: Jerrells, Thomas R.; Professor; Pediatrics; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 01-SEP-1988; Project End 31-MAY-2004 Summary: (Adapted from the Investigator's Abstract) Study results from my laboratory and reported by other researchers have shown that ethanol (ETOH) consumption by experimental animals and human beings is associated with an increased susceptibility to infectious diseases. Overall, this is associated mostly with defects in the generation of cell-mediated immune responses and the effector functions of lymphoid cells, including T and natural killer cells as well as macrophages. We and others have shown that ETOH consumption is also associated with activation of the hypothalamic-pituitary- adrenal (HPA) axis and that many of the changes in lymphoid cell numbers and function can be attributed to the resulting corticosteroids produced as a result of this activation. The general hypothesis to be tested in the studies proposed in this application is that the corticosteroids produced by ETOH-fed animals suppress innate and acquired immune responses that are necessary for host defenses against infectious microorganisms. This hypothesis and other more specific hypotheses resulting from the general hypothesis will be tested by using a murine model of ETOH consumption in a liquid diet with a pair-feeding paradigm. With the use of adrenalectomized mice we will determine whether immune responses to model T-cell-dependent antigens such as phosphocholine conjugated to key hole limpet hemocyananin or infectious microorganisms, including Listeria monocytogenes, Salmonella typhimurium, Nippostrongylus brasiliensis, and murine cytomegalovirus, are decreased by corticosteroids produced as a result of ETOH consumption. With this approach the role of ETOH-associated corticosteroid production on the cellular effectors of immunity, including natural killer cells, CD4+ and CD8+T cells, and macrophages will be tested. By using the various infectious model systems in place in this laboratory the ETOH-mediated effects on the subsets of helper T cells (TH-1 and TH-2) will also be defined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF INDUCTION OF FIBROBLAST APOPTOSIS BY ANTICD44 ANTIBODY Principal Investigator & Institution: Henke, Craig A.; Associate Professor of Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002
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Summary: Intraalveolar fibrosis is a stereotypical reaction to lung injury. However, in many patients this reparative process is ineffective due to failure to adequately eliminate airspace fibrotic tissue or due to progressive fibrosis. Progressive alveolar fibrosis is directly and indirectly one of the leading causes of death in patients with ARDS. Therefore, therapeutic strategies designed to promote regression or elimination of airspace fibrotic tissue as a novel approach for the treatment of patients with ARDS may be effective. Pilot studies suggest that timely intervention with corticosteroids during the repair phase of ARDS may hasten resolution of airspace fibrosis and improve patient survival. Unfortunately, corticosteroid use in this patient population is potentially hazardous due to the increased risk of life-threatening infection. Nevertheless, these studies lend credence to strategies designed to promote regression of airspace fibrosis as a novel therapeutic approach for the treatment of patients with late ARDS. We have discovered that the cell surface matrix receptor, CD44, mediates lung myofibroblast invasion into fibrin matices. Immunohistochemical studies of lung tissue from patients who died with alveolar fibrosis show CD44 expressing mesenchymal cells in newly formed fibrotic tissue linking CD44 with the fibrotic response and implicating CD44 with anti-CD44 antibody triggers lung myofibroblast apoptosis. This suggests that the ligation state of CD44 may play a role in the regulation of fibroblast viability. We have shown that fibroblast apoptosis results in part, but not solely from detachment indicating that anti-CD44 antibody triggers an additional pro- apoptotic signal. Studies have linked apoptosis due to disruption of adhesion with increases in the elevation of cyclin A and activation of cyclin A dependent kinases. Work within our laboratory indicates that ligation of CD44 with antibody is associated with increases in both cyclin A and p21. Preliminary studies indicate that experimental down-regulation of cyclin A and p21 markedly attenuates anti-CD44 antibody induced apoptosis identifying an important functional role for these proteins. In our competing renewal, we plan to examine the molecular basis by which anti-CD44 antibody induces fibroblast apoptosis. Discovery of how ligation of CD44 engages the fibroblast apoptotic pathway may provide insight into the development of therapeutic agents which promote regression of airspace fibrosis in patients failing to recover from ARDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORED DEVELOPMENT AWARD
PATIENT-ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Zeidler, Michelle R.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Asthma is an enormous medical and economic burden worldwide and affects over 14 million Americans. Despite treatment with inhaled corticosteroid therapy, many asthmatic patients exhibit persistent symptoms of asthma, as well as accelerated decline in lung function. While asthma has classically been described as a disease of the proximal airways, physiologic, histologic, and immunologic data indicate that the distal lung is significantly involved in asthma and may be a cause of uncontrolled disease. Understanding the role of the distal lung in asthma has been hampered by difficulties in studying and treating this area. Chlorofluorcarbon (CFC) inhaled corticosteroids (ICS), the mainstay of asthma treatment, cannot effectively reach the distal lung due to their relatively large particle size. The recent transition to non-CFC inhalers has created a new class of extra-fine ICS aerosols which, theoretically, have a sufficiently small particle size to reach this region. To date, the effect of extra-fine ICS on distal lung inflammation remains unknown. The
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proposed study will evaluate the change in distal lung inflammation in mild to moderate steroid naive asthmatics at baseline and after treatment with a conventional ICS which mainly targets the proximal lung versus an extra-fine ICS which targets both the proximal and distal lung. The study will be conducted using a double-blinded, randomized crossover trial design. Before and after treatment, distal lung inflammation will be evaluated using: 1) messenger ribonucleic acid (mRNA) measures of inducible nitric oxide synthase, eotaxin, rantes, and interleukin-4 (IL-4) receptor alpha in distal airways obtained via distal lung brushings; and 2) lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor (TNF)-alpha and MIP-1 alpha by alveolar macrophage obtained from distal bronchoalveolar lavage (BAL) aliquots. Non-invasive measures of small airways disease will also be obtained before and after treatment and correlated with the molecular and cellular markers of distal lung inflammation in an attempt to identify a valid non-invasive marker of small airways inflammation. Noninvasive markers of distal disease include: 1) quantitative analysis of thoracic computed tomography at residual volume (RV) before and after methacholine challenge; 2) physiologic measures of small airways disease including RV, FRC, isovolume FEF 25-75, and closing volume; and 3) the alveolar portion of exhaled nitric oxide (NO). This study will determine the potential to modify distal airways inflammation which may ultimately improve asthma control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODIFICATION OF ALLERGIC IMMUNOLOGIC RESPONSE BY LEUKOT Principal Investigator & Institution: Finn, Patricia W.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's Abstract)Asthma is a chronic inflammatory disease. T lymphocytes are essential for initiating and maintaining the asthmatic inflammatory immune response. Corticosteroid treatment targets several inflammatory responses, including T lymphocytemediated responses. In addition, leukotriene receptor antagonists (LTRA) may influence T cell activation. To investigate the effects of these two controller agents in the treatment of asthma on airway function is the goal of the IMPACT clinical trial mild chronic adult asthmatics. In this proposal we will examine the cellular and molecular mechanisms of corticosteroid and an LT-RA, focusing on their effects on T lymphocytes during both chronic (18 months) and acute therapy. Complete T cell activation during allergen exposure requires antigen signals mediated by the T cell receptor plus costimulatory signals. The best- characterized costimulatory pathway involves the receptors CD28, CTLA4 and ICOS expressed on T lymphocytes and the ligands CD80, CD86 and B7-h expressed primarily on antigen presenting cells. While CD28 is expressed constitutively on most T lymphocytes, CTLA4, ICOS, CD80, CD86 and B7-h are upregulated during an immune response and are the focus of this proposal. We have previously demonstrated that pulmonary inflammation and airway hyperresponsiveness is dependent upon T cell costimulation in a model of allergic asthma. We postulate that the T lymphocyte costimulatory pathway is a critical target for effective asthma therapy. Specifically, our hypothesis proposes that the function of the costimulatory receptors CTLA4 and ICOS and their ligands CD80, CD86 and B7h, will be downregulated after treatment with corticosteroids and/or a leukotriene receptor antagonist (LT-RA) in mild persistent asthmatics. Analyzing samples before and after asthma therapy, Aim 1 will determine the mechanisms by which the costimulatory receptors, CTLA4 and ICOS, are regulated. Aim 2 will investigate changes
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in the immunoregulation of costimulatory ligands, CD80, CD86 and B7-h. Aim 3 will identify differentially expressed T lymphocyte genes using expression array analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR AND CELLULAR ANALYSIS OF AQUAPORIN 1 IN LUNG Principal Investigator & Institution: King, Landon S.; Assistant Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from applicants' abstract) Regulated movement of water in the lung is essential for normal lung function. After years of characterizing lung water dynamics on a gross scale, recent exploration of cellular and subcellular factors contributing to water transport has yielded additional insight into this process. This proposal is an extension of the applicants interest in basic lung biology, specifically, mechanisms of lung water homeostasis. This interest began with studies of acute lung injury and pulmonary hemodynamics in medical school, continued through clinical training in internal medicine, and most recently is being pursued through the study of aquaporin (AQP) water channel proteins. Aquaporins are water specific transmembrane channels, originally identified in red blood cells and renal proximal tubule, but recently shown to have complex ontogeny and distribution in the lung. Distinct nonoverlapping expression of different homologs throughout the respiratory tract suggests a number of potential functions, but also predicts complex regulation. In particular, preliminary studies demonstrate that Aqp1, abundantly expressed in visceral pleura, bronchial circulation, and nasopharyngeal vessels of the rat, can be induced in vitro and in vivo by a variety of physiologically relevant agents. This proposal builds on previous observations made by the applicant, focusing on the molecular and cellular regulation of Aqp1 in models relevant to lung physiology. Three principal lines of inquiry are to be undertaken: I) molecular genetic analysis of the Aqp1 promoter in mouse; II) in vitro characterization of molecular mechanisms regulating aqp1 expression in response to corticosteroids, hypoxia, and hyperosmalarity; and III) generation of Aqp1 null transgenic mice for subsequent characterization of the phenotype. The proposed studies are to be carried out at Johns Hopkins under the mentorship of Dr. Peter Agre, who discovered water channel proteins and continues to lead the field in their investigation. The environment at Johns Hopkins greatly facilitates this type of investigation, as both support and stimulation are abundantly present. The candidate has recently worked in Dr. Agre's laboratory but now wishes to undertake a distinctly different line of investigation, a molecular genetic approach to regulation of Aqp1 expression. These studies should enhance the understanding of the molecular mechanisms regulating lung water homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR REGULATION OF ILEAL/RENAL BILE ACID TRANSPORT Principal Investigator & Institution: Shneider, Benjamin L.; Associate Professor of Pediatrics; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 30-SEP-1997; Project End 31-MAR-2007 Summary: (provided by applicant): The apical sodium-dependent bile acid transporter (ASBT) is the major carrier protein involved in intestinal reclamation of bile salts.
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Complete genetic disruption of its activity leads to pathologic bile acid induced diarrhea in humans, while partial inhibition can be used to treat hypercholesterolemia and cholestasis. ASBT is expressed on the apical surface of ileal enterocytes, renal tubules, and cholangiocytes. In the rat ileum, ASBT undergoes a biphasic pattern of developmental expression. Bile acid responsiveness of ASBT is species specific. ASBT is down regulated in the ileitis and up regulated by corticosteroids. Adaptation by ASBT after intestinal resection is dependent upon the length of residual ileum. These changes in ASBT expression are controlled at the level of transcription and mRNA stability. The rat, mouse, and human ASBT promoters have been cloned in my laboratory. HNF1alpha, AP-1 and LRH-1 are critical elements in the transcriptional regulation of ASBT. This proposal will define the molecular mechanisms involved in the regulation of the ASBT gene. Transcriptional regulation will be studied with chimeric luciferase promoter reporter constructs, DNA:protein gel shift analysis, and transgenic mice. Molecular mechanisms of transcriptional modulation of ASBT gene expression will be analyzed in normal physiology and pathologic states (altered bile acid homeostasis, ileal inflammation and intestinal resection). The role of mRNA stability will be assessed by identification of mRNA destabilizing elements in the ASBT transcript and by characterization of RNA:protein interactions. Cell-free systems and/or transgenic animals will be utilized to assess the role of these elements in developmental-stage and organ specific expression. The results of these studies will be highly significant in light of the crucial role that ASBT plays in human health and disease. The ASBT gene also represents a valuable model of important and poorly defined biological processes in the intestine, such as transcriptional regulation of ontogeny and tissue specificity and the role of mRNA stability in intestinal gene regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTICENTER TRIAL OF FOCAL GLOMERULOSCLEROSIS Principal Investigator & Institution: Gipson, Debbie S.; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Idiopathic focal segmental glomerulosclerosis (FSGS) is a progressive scarring disorder that causes proteinuria and kidney failure in the majority of affected individuals. There is considerable controversy regarding the best therapeutic intervention and the definition of pathological variants of FSGS that may impact therapeutic response rates. This proposal focuses on the design and conduct of a collaborative multicenter trial that will evaluate response rates of children and young adults with the nephrotic syndrome due to FSGS treated with cyclosporin A as compared to corticosteroids plus angiotensin receptor blocker therapy. It will utilize a newly determined FSGS classification scheme as defined by the NY Pathology Consensus Group that includes one of our collaborators. In addition, since incidence of idiopathic FSGS has been increasing over the past 2 decades, a case-control study that will evaluate risk factors for FSGS is proposed to run concurrently with the trial. Our proposed southeastern clinical coordinating center will provide strength to the planned nation-wide trial through our large patient population with FSGS, the strength of the UNC nephropathology service, and the investigators' long track record of clinical trial and epidemiologic research in glomerular diseases through the UNC-Chapel Hill based Glomerular Disease Collaborative Network. In conjunction with committed collaborating sites, our group has over 400 FSGS patients who would be eligible for the proposed trial, as well as established mechanisms for including prospectively identified patients. The proposed case-control study will evaluate risk factors for the development
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of FSGS such as body mass, birth weight, viral illnesses and smoking in all patients screened for entry into the trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPEPTIDE Y FOR CANCER-ASSOCIATED ANOREXIA Principal Investigator & Institution: Jatoi, Aminah; Assistant Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Over 60% of patients with advanced cancer suffer from anorexia, or loss of appetite. Cancer patients describe it as their 3rd most noxious symptom, outranked only by pain and fatigue. Yet palliative options are limited. The two most commonly prescribed orexigens are progestational agents and corticosteroids. Independent of a placebo effect, however, only 20% of cancer patients describe appetite improvement with their use. Neuropeptide y (NPY) offers a novel approach. Two pieces of evidence justify further study of this naturally occurring hormone in this setting. First, our group found that advanced cancer patients with severe anorexia (defined as < 50% of their premorbid intake, as measured by a validated questionnaire) manifest lower circulating concentrations of NPY compared to historical controls, a finding which raises the possibility that hormonal repletion may improve appetite. Second, even in non-tumor-bearing animals, NPY is "the most potent feeding stimulus known." Both direct NPY-receptor interactions within the brain's feeding centers and alterations in the body's hormonal milieu may account for these orexigenic effects. We propose 2 pilot studies to allow us to begin testing NPY for cancer-associated anorexia. First, we will test the hypothesis that a biologically active, relatively non-toxic dose of NPY can be administered. We propose a phase I trial with an estimated maximum of 36 advanced cancer patients to evaluate changes in cortisol, adrenocorticotropic hormone (ACTH), and leptin as well as toxicity and systemic exposure of intranasal NPY. Second, because NPY's orexigenic effect may be receptor-mediated, we will test the hypothesis that NPY Y1 and Y5 receptor polymorphisms are associated with anorexia in cancer patients independent of serum NPY. We propose a case control study (75 patients/group) to explore associations between these polymorphisms and anorexia and will incorporate these polymorphisms as stratification/adjustment factors in larger, future NPY trials should such associations be found. These two pilot studies will allow us to lay the groundwork for such larger trials. Our ultimate goal is to help cancer patients who suffer from anorexia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL CRF ANTAGONISTS FOR INFLAMMATION AND PAIN Principal Investigator & Institution: Lindner, Mark D.; Neurocrine Biosciences, Inc. 10555 Science Center Dr San Diego, Ca 921211100 Timing: Fiscal Year 2002; Project Start 20-JUN-2002; Project End 31-MAY-2003 Summary: (provided by the applicant): Inflammation and pain affect large and everincreasing patient populations. Narcotics, corticosteroids, and NSAIDs are effective, but they are associated with tremendous adverse effects which now account for thousands of deaths each year. The long-term objective of this proposal is to develop a CRF receptor antagonist as an analgesic andanti-inflammatory agent with a novel mechanism of action, with equivalent anti-inflammatory and analgesic effects and an improved side-effect profile compared to currently available treatments. In preliminary experiments we have shown that tissue-resident mast cells in inflamed tissues have CRF
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Corticosteroids
receptors, and that CRF antagonists attenuate activation of these mast cells and produce robust analgesic effects. In Phase I, using rodent models of acute and chronic inflammation, we propose to determine if the analgesic effects of CRF antagonists can be attributed entirely to peripheral CRF-R1 receptors, if the analgesic and antiinflammatory effects of CRF antagonists are detectable in chronic as well as acute inflammation, and if CRF antagonists are effective and have a low side-effect profile even after chronic administration. Phase II will focus on the medicinal chemistry, in vitro and in vivo biology needed to produce a small molecule CRF antagonist with optimal characteristics for the treatment of inflammatory disorders. PROPOSED COMMERCIAL APPLICATION: This research, if successful, will result in small molecule antagonists of the corticotropin releasing factor receptor with maximum potency for anti-inflammatory and analgesic effects. Orally active forms of a small molecule CRF receptor would provide a novel therapeutic strategy for indications of acute and chronic inflammation and inflamatory pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL CORTICOSTEROIDS
VEHICLE
FOR
TOPICAL
DELIVERY
OF
Principal Investigator & Institution: Rawls, H. Ralph.; Professor and Head; Biomedical Development Corporation 500 Sandau, Ste 200 San Antonio, Tx 78216 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Topical corticosteroids are useful treatment modalities for numerous dermatologic conditions. Most topical corticosteroids are applied in a cream or ointment vehicle, which require multiple applications, are subject to inadvertent removal, and can be cosmetically unacceptable. While efficacy has been shown to be increased with the use of hydrocolloid occlusive dressings, these dressings are often associated with local side effects and inherent cosmetic deficiencies. The goal of this project is to demonstrate the feasibility of using a novel coating technology as a topical delivery vehicle for corticosteroids that simultaneously serve as a semi-occlusive dressing. Coatings impregnated with corticosteroid will be formulated and tested to demonstrate efficacy in the vasoconstrictor assay in humans. PROPOSED COMMERCIAL APPLICATION: Topical corticosteroids are the most widely used preparations in dermatology. A novel vehicle that could improve efficacy and reduce treatments while being cost-effective would have significant commercial potential. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPTIMIZING REFRACTORINESS
TREATMENT
FOR
TTP
AND
PLATELET
Principal Investigator & Institution: Mc Farland, Janice G.; Vice President, Medical Affairs; Blood Center of Southeastern Wisconsin Milwaukee, Wi 532012178 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Study I: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of uncertain etiology that causes multi-organ dysfunction due to occlusion of small blood vessels by microthrombi. Over the past three decades plasma therapy has reduced the mortality rate from nearly 100% to about 20%. Although most patients recover from the initial episode, the relapse rate is high, and TTP remains a disease with substantial morbidity and mortality. Recent discovery of an association between decreased yon Willebrand factorcleaving protease (vWCP) levels and disease activity together with the demonstration of an autoantibody directed at this protein in
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some patients, raise the possibility that additional immunomodulatory therapy may be of benefit. We propose a randomized study comparing plasma exchange to plasma exchange plus corticosteroids to test the hypothesis that corticosteroids will increase the rate of durable complete responses. We also propose to determine if splenectomy will decrease the subsequent relapse rate in patients who have experienced a relapse of TTP. Studies correlating vWCP levels to disease activity and additional laboratory studies characterizing other possible disease correlates are planned. Study II: Prevention strategies for platelet alloimmunization and accompanying platelet transfusion refractoriness are not completely effective, particularly in individuals previously exposed to HLA and platelet antigens through transfusion of non-leukocyte reduced blood products or pregnancy. Selecting platelet products to avoid a refractory patient's alloantibody response is a mainstay of transfusion support for these patients but there is no consensus on which selection strategy is most effective for this clinical problem. We propose to compare the effectiveness of platelet crossmatching with HLA matching in providing platelet transfusion support to patients who are refractory to random donor platelet transfusions. In this context we will also determine the extent to which factors unrelated to HLA or platelet-specific alloimmunization (non-immune factors, ABO incompatibility) influence platelet transfusion responses. This information will be extremely useful in designing effective and cost-efficient platelet transfusion protocols for refractory patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS OF HERPETIC KERATITIS Principal Investigator & Institution: O'brien, William J.; Ophthalmology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (from abstract). Corneal infections with herpes simplex virus (HSV) are estimated to affect 400,000 individuals in the U.S. and over 20,000 new cases present annually. This application focuses on the mechanism(s) by which HSV infections induce corneal edema, the most common complication of herpetic keratitis. We propose that HSV-induced edema results from inhibition of corneal endothelial cell Na+K+ATPase by products of an inducible nitric oxide synthase (NOS). NOS2 is induced and regulated by cytokines produced during HSV infections and products of this enzyme, nitric oxide (NO) and its metabolites, can alter the function of proteins including Na+K+ATPase. Aim 1 is to measure corneal endothelial cell Na+K+ATPase during development and recovery from HSV-induced edema in a rabbit model. Pump function will be measured by rubidium uptake and enzyme activity by phosphate release from ATP. ATPase subunit mRNA will be quantitated by RT-PCR using mimics and standard curve methodology. Western blots of endothelial cell extracts from edematous corneas will be used to detect nitrotyrosine residues in the ATPase, definitive evidence of the action of NOS2 products. Aim 2 will determine which cell types in the anterior segment express NOS2 during disease. NOS2 assays will measure the Ca+-independent conversion of Langinine to L-citrulline. RT-PCR will be used to estimate changes in steady state NOS messages from all three NOS isoforms. In situ hybridization will be used to locate and tentatively identify cells expressing NOS2. Aim 3 is to assess the effects of NO production on endothelial cell function. The effects of exogenously generated NO upon endothelial cell function in vivo will be evaluated by measuring corneal thickness, endothelial cell number, ouabain binding, and barrier function. NO generators and inducers of NOS2 will be used to determine the effects of NO on Na+K+ATPase activity in cultured cells. The nitration of proteins in corneal cells will be examined using
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Corticosteroids
immunochemical methods and electron spin resonance. Aim 4 will determine the effects of regulators on Na+K+ATPase and NOS2 activity in corneal cells in vivo and in vitro. The results of these studies will determine whether NO generated by NOS2 is responsible for HSV-induced corneal edema and whether NOS isoforms or NOregulated functions contribute to the pathogenesis of this disease. The long-term goal is to understand the pathogenesis of edema in order to develop effective and specific alternatives to corticosteroids for the therapy of HSV-induced edema and stromal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEDIATRIC ASTHMA CLINICAL RESEARCH NETWORK-CLINICAL CTR Principal Investigator & Institution: Strunk, Robert C.; Professor of Pediatrics; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Research in the pathophysiology and epidemiology of asthma has guided development of treatments that are effective in management of symptoms and improving pulmonary function in children. However, there are many significant questions that remain to be addressed about asthma management. This proposal will address two of these important issues. In the first propose a 3-year randomized, doubleblind trial comparing the effects of four treatments on chronic airway obstruction in children with asthma 5-15 years of age: 1) high dose inhaled steroid (IS) + leukotriene receptor antagonist (LA), 2) high dose IS alone, 3) low dose IS + LA, and 4) low dose IS alone. Chronic airway obstruction is defined as an abnormal FEV1/FVC after maximal bronchodilation on 2 occasions separated by 6-8 weeks. Primary hypothesis: Compared to low dose IS alone, high dose IS + LA will improve post bronchodilator FEV1 and FEV1/FVC over three years of study, taking into consideration age, gender, race, duration of asthma on entry into the trial, initial FEV1, and initial FEV1/FVC. Effects of high dose IS alone and low dose IS + LA will be intermediate. In the second, we propose a nine month randomized, double-blind, placebo-controlled prospective trial comparing three therapeutic approaches to young children (1-3 years of age) with mild intermittent asthma and recurrent viral respiratory infection-induced wheezing episodes: 1) inhaled bronchodilators at inception of a URI syndrome, 2) inhaled bronchodilators and high dose nebulized inhaled steroid (IS) at inception of a URI syndrome, and 3) ongoing low dose IS with inhaled bronchodilators and high dose nebulized IS at inception of a URI syndrome. For each of the groups, if symptoms progress, as defined by development of wheezing and/or cough unresponsive to inhaled bronchodilators, oral systemic steroids will be added. Primary hypothesis: Compared with the conventional therapy consisting of the sequential addition of systemic corticosteroids to inhaled bronchodilators (Group 1), early intervention with IS at the onset of symptoms suggestive of a URI will decrease the total number of days with wheezing over a 7 month period. The administration of high dose IS at the onset of URI symptoms (Group 2) will be at least as efficacious as the administration of low dose IS as maintenance therapy with high dose IS added at first sign of URI symptoms (Group 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHARMACOGENETICS OF ASTHMA MONOTHERAPY Principal Investigator & Institution: Lima, John J.; Professor; Nemours Children's Clinic 807 Children's Way Jacksonville, Fl 322078482
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Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Asthma is a chronic inflammatory disease of the airways that is caused by a complex interaction between genetic and environmental factors. In the US, more than 11 million individuals reported having at least one attack of asthma in 2002, and the number of people with asthma is expected rise to 29 million by 2020. Given the significant mortality, morbidity and economic impact of asthma, it is important to improve treatment of the disease and to develop new strategies and drugs for intervention. Most of the drugs used to control asthma symptoms fall into 3 pharmacological classes: inhaled corticosteroids (ICS), leukotriene receptor antagonists (LTRA) and long-acting beta adrenergic receptor agonists (LABA). Clinical trials have established the efficacy and safety of these drugs alone or in combination to treat asthma. However, marked inter-patient variability in response to each of the drugs limit their safety, efficacy and cost-effectiveness. Recent studies suggest that up to 80% of the inter-patient variability in response to asthma drugs is due to genetic variation. The American Lung Association Asthma Clinical Research Centers are performing a clinical trial entitled: LeukotrieneModifier or Corticosteroids (LOCS) trial. Patients 6 years or older with asthma who are stable on inhaled fluticasone (FP) monotherapy for 4 to 6 weeks, will be randomly assigned to continue taking inhaled FP, 100 ug twice a day, OR montelukast, 10 mg at bedtime, OR inhaled salmeterol, 50 ug twice a day, for 16 weeks. 165 patients will participate in each treatment arm (495 total). The LOCS trial was designed to determine if montelukast monotherapy and salmeterol monotherapy can be substituted for inhaled FP without loss of asthma control. The primary outcome is asthma control as determined by the rate of treatment failures with montelukast monotherapy and salmeterol monotherapy compared to inhaled FP. Secondary outcomes include pulmonary function, asthma symptoms including medication use, patient related measures, markers of inflammation and in 200 patients, airway responsiveness to methacholine. The goals of the present ancillary pharmacogenetic study are to identify SNPs in one or multiple genes that predict which patients can be treated with either montelukast or salmeterol monotherapy without loss of control conferred by inhaled FP. The results of this pharmacogenetic study may facilitate the optimal selection of monotherapy in asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PODOCYTES & STRESS RESPONSE IN NEPHROTIC SYNDROME Principal Investigator & Institution: Smoyer, William E.; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: Nephrotic syndrome is one of the most common forms of kidney disease in children. It is characterized by massive leakage of protein across the kidney's filtration barrier and dramatic structural changes in podocytes, which in part comprise the barrier. These changes include retraction (effacement) of the actin-rich podocyte foot processes with disruption of their actin filaments, and can be attenuated by treatment with reactive oxygen molecule scavengers, suggesting a link between NS and oxidant injury to podocytes. We recently detected a reported regulator of actin polymerization, heat shock protein 27 (hsp27), in normal podocytes, and reported induction of hsp27 in glomeruli during NS. We hypothesize that hsp27 has an important role in mediating the podocyte structural changes which occur in NS, via regulation of actin filament dynamics. We also hypothesize that hsp27 has an important role in the podocyte response to oxidant stress, and that the therapies commonly used to treat NS act by
56
Corticosteroids
protecting podocytes from oxidant-induced injury via alterations in hsp27 expression and/or phosphorylation. To test these hypotheses we will: 1) Determine if induced changes in podocyte hsp27 expression and/or phosphorylation protect against NS, 2) Identify glomerular hsp27-binding proteins and measure changes in the interaction between hsp27 and the identified proteins during NS, and 3) Measure the protective effects of induced alterations in podocyte hsp27 on the podocyte stress response, and compare these effects to those resulting from podocyte treatment with corticosteroids, cyclosporine A, and cyclophosphamid (common treatments for NS). We will use both in vivo (PAN nephrosis in rats) and in vitro (PAN and protamine treatment of cultured "differentiated" podocytes) models of NS to determine if induction of hsp27 in vivo (whole animal hyperthermia, hsp27 transgenic animals) or in vitro (hsp27 sense/antisense/phosphorylation mutant stable transfections) protects podocytes against foot process effacement and NS. A yeast two hybrid library from rat kidney glomeruli will be used to identify, and define hsp27-binding proteins, and alterations in their interactions with hsp27 during NS will be determined by biochemical analyses. Cultured "differentiated" podocytes transfected with hsp27 sense/antisense/phosphorylation mutants will be treated with stressors with specific biological relevance to NS (oxidant stress, actin filament disruption, heat shock) and the cellular stress response (survival, actin filament structure, induction of hsps and antioxidants) compared to that after treatment with drugs used for NS. Identification of a biologically important role for hsp27 in regulating podocyte structure in NS would permit the development of more highly targeted and less toxic therapies for this very common form of kidney disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRENATAL CORTICOSTEROID IMPACT ON HIPPOCAMPUS Principal Investigator & Institution: Velisek, Libor; Associate Professor; Neurology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Corticosteroid therapy is widely used during the third trimester of pregnancy to prevent respiratory distress syndrome in prematurely born neonates. A single course of this therapy has no long-term harmful effects. However, multiple courses of corticosteroid therapy with long-lasting elevations of corticosteroids are frequently used. Animal data indicate that long-term prenatal corticosteroid increases during the last third of pregnancy may adversely affect brain development, especially hippocampus-associated functions such as learning and memory. The purpose of this proposal is to establish a rat model of prenatal or early postnatal multiple-course corticosteroid administration to determine the effects of repeated corticosteroid therapy on hippocampal function (tested postnatally in hippocampal- related seizure susceptibility, behavioral and learning tests in vivo) and morphology (assessed using neuronal proliferation, stereological neuronal counts, and rate of neuronal death). The proposal will further investigate the possibility that there may be a synergy between the effects of such doses of corticosteroids that do not produce harmful effects and the effects of another subthreshold postnatal impact (a febrile seizure). The synergy of these two factors will then result in adverse effects on hippocampal function and structure ("two-hit" hypothesis). Finally, the experiments will determine whether the harmful effects of repeated corticosteroid treatment may be ameliorated by the exposure of the affected offspring to an enriched environment. Methods include prenatal administration of corticosteroids, kainic acid-induced seizures, hippocampal kindling, open field, horizontal bar and elevated plus maze tests,
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labeling of newly born neurons with BrdU, fluorescent staining for apoptotic/necrotic neurons, stereological neuronal counts in the hippocampus using light and confocal microscopy, and the exposure of the rats to an enriched environment. The data of this proposal will be critical for determining long-term adverse effects of multiple course prenatal corticosteroid therapy and for the ameliorating these effects in the offspring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRIMATE ENDOCRINE REGULATION IN THE PERINATAL PERIOD Principal Investigator & Institution: Jaffe, Robert B.; Professor and Director, Center; Obstetrics, Gynecology & Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUN-1978; Project End 30-NOV-2003 Summary: The goal of these studies is to elucidate the developmental biology of the human fetal adrenal gland. Our underlying hypothesis is that the unique structure, rate of growth and steroidogenic function of the human fetal adrenal is the net effect of ACTH secreted from the fetal pituitary and a cohort of growth factors expressed by the fetal adrenal of which insulin-like growth factor-II (IGF-II) is a major component. Based upon our preliminary findings and those of others, our specific aims are to determine: the mechanisms by which the fetal adrenals grows; the functions of the various cortical zones; the mechanism by which ACTH regulates growth and function; and the role of IGF-II in fetal growth and function. Understanding the growth and differentiation of the fetal adrenal gland is to cardinal importance because of 1) the pivotal role adrenal corticosteroids play in early enzyme induction, the coordinate development of independent organ systems necessary or intrauterine homeostasis and extrauterine survival (e.g. feta lung maturation, deposition of glycogen in the fetal liver, and induction of enzymes in the fetal brain, thyroid, gastrointestinal tract and retina), the response to intrauterine and perinatal stress; 2) the pathologic alteration of growth that occurs in congenital adrenal hyperplasia, which we hypothesize is the result of the overexpresion of locally produced growth factors stimulated by excess ACTH; 3) the atavistic reversion to a fetal mode of function in adult adrenal neoplasms; and 4) the insights into more general aspects of human organ growth that this understanding will provide. We will utilize cell culture and molecular biological techniques, as well as two newly develop;ed in vivo models (fetal adrenal tissue grafted under the kidney capsule of the athymic mouse and endogenous stimulation of the hypothalamic-pituitaryadrenal axis of the fetal rhesus monkey) to address our specific aims concerning the developmental biology of the human fetal adrenal gland. The proposed studies are to investigate specific aspects of growth and differentiation in the human fetal adrenal with the aim of determining the mechanism by which these processes are regulated. Ultimately, these adrenal with the aim of determining the mechanisms by which these process are regulated. Ultimately, these studies should contribute to knowledge of the role of the fetal adrenal in intrauterine development and homeostasis, the regulation of normal and altered human pregnancy, as well as greater understanding of the mechanisms of trophic hormone action on target tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROSTANOIDS AND THEIR RECEPTORS IN ASTHMA Principal Investigator & Institution: Koller, Beverly H.; Associate Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003
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Corticosteroids
Summary: (Applicant's Abstract) Eicosanoids, products of arachidonic acid (AA) metabolism, are potent modulators of the inflammatory response. A significant role for these lipid mediators in the pathogenesis of asthma has been demonstrated, and drugs targeting one branch of this pathway, the leukotriene pathway, have recently been developed and added to our therapeutic armamentarium against asthma. A number of studies have suggested that prostanoids, cyclooxygenase (COX) metabolites of AA, have a significant impact on inflammation in asthmatic patients. The most extensively studied of these is PGE2. A number of lines of evidence suggests that PGE2 plays a significant anti-inflammatory role in asthma, and might produce many of the same beneficial effects observed on treatment with corticosteroids. Moreover, PGE2 has been shown to have not only immunomodulatory actions, but bronchodilatory effects as well. While all other prostanoids are thought to act through a single cell surface receptor specific for that prostanoid, four receptors for PGE2 have been identified and cloned, and have been termed EP1-EP4. Each receptor subtype binds PGE2 with equal affinity, but these receptors can trigger unique signal tranduction pathways, which in turn can evoke opposing physiologic actions. Most cells express a unique combination of EP receptor subtypes, and the physiologic response of that cell to PGE2 is determined by the subset of receptors expressed. The therapeutic potential of PGE2 has not yet been exploited in part due to this complex physiology. The overall aim of this proposal is to evaluate the contribution of PGE2, through each of these the receptors, to the pathogenesis of allergic airway disease and to determine the potential of both PGE2 and the four EP receptors as therapeutic targets for the treatment of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RANDOMIZED TRIAL OF ROSIGLITAZONE FOR ULCERATIVE COLITIS Principal Investigator & Institution: Lewis, James D.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Ulcerative colitis (UC) is a chronic inflammatory disease involving all or a portion of the colon. Currently, there are few effective medical therapies for UC. Furthermore, because of the potential toxicity of the currently available agents, there is a great need for alternative therapies to treat patients with UC refractory to therapy with 5-ASA agents. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of transcription factors whose activities are regulated by high affinity binding of small lipophilic ligands such as steroid hormones. A new class of diabetic drugs, the thiazolidinediones, has been developed to bind to the gamma (g) subtype of the PPARs. Colonic epithelial cells express high levels of PPARg protein and have the ability to produce inflammatory cytokines that may contribute to the inflammatory process in UC. We have previously demonstrated that PPARg ligands significantly attenuate cytokine gene expression related to the inflammatory cascade in colon cancer cell lines. Furthermore, we and others have demonstrated that thiazolidinedione ligands for PPARg markedly reduce colonic inflammation in murine models of ulcerative colitis. In addition, we have shown in a pilot study that more than 50% of patients with mild to moderately active UC despite therapy with 5-ASA agents (and corticosteroids or imunomodulator medications for most patients) experienced improved symptoms within 12 weeks of therapy with rosiglitazone 4 mg twice daily. As such, we believe that PPARg may represent a novel target for modulating colonic inflammation in UC. The proposed study is a multi-center, double-blind, randomized controlled trial of rosiglitazone versus
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placebo for mild to moderately active ulcerative colitis refractory to standard therapy with oral 5-ASA agents. 176 subjects will be randomized to rosiglitazone 4mg bid or placebo for 12 weeks of therapy. The primary outcome will be improvement in disease activity as measured by the Disease Activity Index first described by Sutherland. Secondary outcomes will include clinical remission and quality of life. We will use the techniques of immunohistochemistry to detect expression of PPARg receptors in human colon tissue. We will also use the technique of immunohistochemistry to examine the change in NF-KB activation prior to and following therapy with either placebo or rosiglitazone. Specifically, we will compare expression of p65 and phosphorylated IKBalpha, in colonic tissue prior to and following exposure to rosiglitazone and placebo. If our hypothesis is correct, this study will serve to establish that ligands for PPARg possess biological activity necessary to modulate the inflammatory response in the intact human colon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF BRAIN NEUROPEPTIDE / RECEPTOR SYSTEMS Principal Investigator & Institution: Dorsa, Daniel; Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-DEC-1983; Project End 31-JUL-2004 Summary: Neuroendocrine neuropeptides such as vasopressin, oxytocin, and neurotensin serve as neurohormones, and neurotransmitters in the mammalian brain. The expression of the genes which encode these peptides, and their receptors, in brain neurons is regulated by steroid hormones such as estrogen, corticosteroids, and testosterone. This laboratory has for several years attempted to understand the importance of this hormonal modulation in the function of these neuropeptide systems, has used them to understand the cellular and molecular events which mediate the effects of steroids on neurotransmitter gene transcription in brain neurons. Data gathered in neuroblastoma cells, in primary neuronal cultures, and in the rat and mouse brain in vivo suggests that estrogen acts not only through the "classical" mechanism of action involving nuclear hormone receptor dimerization and binding to consensus hormone response elements, but also via "cross-talk" with other protein kinasedependent signal transduction pathways such as protein kinase A, and the mitogen activated protein kinases. The studies proposed in this renewal application will test the hypothesis that estrogenic regulation of neuropeptide gene expression in vitro and in vivo. They will also investigate the relative roles of estrogen receptor-subtypes (ERalpha and the newly identified ERbeta) in these responses involves a mix of "classical" and protein kinase-dependent transcriptional actions. It is, thus, the combination of these effects which confer the dramatic effects of hormones such as estrogen on the brain involved in neuroendocrine regulation, reproductive behavior, as well as neurotropic effects in the developing and aging. The approach will involve identification of signal transduction cascades which respond to estrogen, determination of their ability to enhance transcription of neuropeptide/receptor promoter-reporter gene constructs in vitro, and profiling their sensitivity to estrogen receptor agonists and antagonists. Local implantation of ER agonists and antagonists, and pharmacologic agents which activate or inhibit the relevant signal transduction pathways will be used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PICROLIV IN ANGIOGENESIS AND WOULD HEALING Principal Investigator & Institution: Maheshwari, Radha K.; Professor of Pathology; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852
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Timing: Fiscal Year 2002; Project Start 10-SEP-2001; Project End 31-MAR-2005 Summary: (APPLICANT'S ABSTRACT): Tissue repair and wound healing are complex processes involving clotting, fibrin-fibronectin deposition, inflammation, reepithelialization, neovascularization, fibroplasia, and wound contraction. Interactions of different cell types, extracellular matrix proteins and their receptors are involved in these biological significant processes, which are mediated by cytokines and growth factors. In the normal host, wound healing is usually uncomplicated and proceeds at a rapid rate. In contrast, most healing failures are associated with some form of host impairment, including diabetes, infection, immunosuppression, obesity, or malnutrition. Wound healing studies that focus on models of impaired healing, therefore, have greater clinical relevance. Diabetes probably represents the prototype of impaired healing models since multiple factors contribute towards the impairment, including peripheral vascular disease, sensory and autonomic neuropathy, and lowered immunity against infections. Recently, we have shown that treatment with a novel pharmacological agent picroliv, resulted in enhanced proliferation and migration of endothelial cells in an ex-vivo model of angiogenesis. Picroliv treatment also increased expression of growth factors that regulate the angiogenic process. The objective of this proposal is to understand effectiveness and underlying mechanism of angiogenic agent picroliv for the better management of chronic and diabetic wounds. To accomplish this objective, we plan to study the effect of picroliv on the growth of human vein endothelial cells. Cell viability and cytotoxicity studies will include cell morphology and lactate dehydrogenase (LDH) activity. We will examine whether picroliv enhances angiogenesis in an in-vitro and in vivo model of angiogenesis. We will use genetically diabetic mice models of impaired healing for our study. Additionally, it is well known that the anti-inflammatory and immunosuppressive activities of corticosteroids suppress healing. We will therefore use animal models wherein healing has been impaired by treatment with steroids. Several wound healing parameters such as wound width and gap, vessel formation, collagenization, apoptosis will be studied in tissues obtained from these models. The regulation of growth factors viz. TGFb-1, bFGF, PDGF, IGF-1 and adhesion molecules will be examined in the wound tissue by immunohistochemistry, RT-PCR as well as by in situ hybridization. Further, to understand the molecular mechanism of action of picroliv, we will examine the profile of metalloprotienases such as MMPl, MMP9, MMP2, and their tissue inhibitors (TIMPs) in the wound tissue by gelatinography and PCR. We believe that these studies will provide information regarding the mechanism(s) underlying the angiogenic effects of picroliv in better management of chronic wounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOXICITY
STEROID
AS
CYTOPROTECTANTS
AGAINST
OXIDATIVE
Principal Investigator & Institution: Chen, Qin M.; Associate Professor; Pharmacology and Toxicology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Stress is known to cause an increase in the synthesis of corticosteroids by the adrenal glands. Although corticosteroids have been shown to contribute to the pathophysiology of suppressed Immune response and a number of psychiatric disorders, the effect of CT on the heart remains unclear. Doxorubicin (Dox) is an anti-neoplastic drug that can produce chronic cardiac toxicity which is manifested as dilated cardiomyopathy. An important feature of this form of cardiomyopathy is the apoptosis of cardiomyocytes. Our preliminary studies found that corticosterone (CT)
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pretreatment prevented Dox from inducing apoptosis of cardiomyocytes. The glucocorticoid receptor antagonist mifepristone prevented CT from inducing a cell survival response. Several forms of g!ucocorticoids, aldosterone, progesterone and retinoic acid but not estrogen, testosterone or L-thyroxin can inhibit apoptosis of cardiomyocytes. Analyses of ERK, Akt and SGK-1 activities or bcl-2 expression indicated that CT neither activated the known survival kinases nor elevated the expression of the anti-apoptotic gene bcl- 2. The conditioned medium of CT-treated cardiomyocytes shows partially cytoprotective effective. The TranSignal array approach found that CT treatment could potentially activate 21 transcription factors. We hypothesize that activation of the glucocorticoid receptor initiates transcriptional activation of survival genes in cardiomyocytes in vitro and in vivo. Specific aims of this grant include: 1) To test if CT binding causes its receptor to interact with and to activate multiple transcription factors in cardiomyocytes; 2) To test that the activation of cell survival genes contributes to CT-induced cytoprotection; and 3) To demonstrate that CT protects the heart from cardiomyopathy induced by Dox in vivo via inducing the transcription of cell survival genes. This project will combine our expertise in genomics, transcriptomics and proteomics to systematically study the linkage between the glucocorticoid receptor and cell survival mechanisms. Given the fact that stress is unavoidable in our daily life, this project will provide novel information to advance our understanding in the biological effect of corticosteroids on the heart. More importantly, since apoptosis has been shown to contribute to heart failure induced by the chemotherapy agent Dox as well as by many forms of cardiovascular disease, our finding and proposed mechanistic study will provide a hope for novel therapy against heart failure in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROIDS AND PATHOGENESIS IN ARDS Principal Investigator & Institution: Goodman, Richard B.; Associate Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant): The acute respiratory distress syndrome (ARDS) is a devastating process of rapidly progressive and severe respiratory failure. One of the major challenges in ARDS research is understanding why the intense underlying inflammatory and fibroproliferative processes resolve rapidly in the lungs of some patients, yet continue for prolonged periods in patients with persistent ARDS. The ARDSNet consortium of clinical investigators have enrolled over 100 patients with persistent ARDS in a randomized, double-blind, placebo- controlled trial examining the effects of corticosteroids on clinical outcomes. Bronchoalveolar lavage fluid (BALF) and plasma are collected at entry and again after 7 days of treatment with corticosteroid or placebo. The GOALS of this proposal are to measure the concentrations of selected cytokines and certain biological activities in BALF and plasma samples, selected for their relevance to three distinct pathological processes of persistent ARDS: 1) persistent acute inflammation, 2) fibroproliferation, and 3) capillary proliferation (angiogenesis), and to relate these processes to clinical and biochemical measures of lung function and outcome. We propose a hypothesis- driven approach to the analysis of these data that will relate each of these cytokines to specific end-points predicted by their known biological activities in-vitro. Results from this work will provide important new information on predictors of steroid responsiveness, and the molecular mechanisms and pathogenesis of persistent inflammation, fibroproliferation and angiogenesis in persistent ARDS.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRESS REGULATION OF 5HT RECEPTORS AND THE HPA AXIS Principal Investigator & Institution: Lopez, Juan F.; Associate Professor; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant) The goal of this proposal is to study the regulation and interaction of specific molecules of the Serotonrn (5HT) system and the LimbicHypothalamic-Pituitary-Adrenal (LHPA) axis in key regions of the rat brain (hippocampus, hypothalamus, and prefrontal cortex); using biochemical and neuroanatomical tools. Dysfunction of the 5HT system and overactivity of the LHPA axis are two of the most replicated biological fmdings in depression. Our overall hypothesis is that the alterations in these two systems are closely linked. Specifically, based on our previous animal and human postmortem studies, we propose the following hypotheses: 1) that glucocorticoids play a central role in the 5HT and corticosteroid receptor dysregulation found in depression and in chronic stress; 2) that failure of an antidepressant to prevent the LHPA overactivity is associated with a failure to reverse these receptor changes; 3) that blocking the effect of glucocorticoids in brain will prevent the receptor abnormalities; and 4) that environmental factors early in life can contribute to LHPA 'dysfunction' and 5HT receptor abnormalities. To answer these hypotheses, on Aims 1 and 2 we will use rats to investigate whether chronic stress causes concomitant changes in brain 5HT, corticosteroid, and CRH receptors. We will also investigate whether antidepressants prevent these changes, and whether circulating corticosteroids have a central role on these stress-induced receptor 'abnormalities'. Aim 3 will investigate whether administration of DHEA, an androgen with antiglucocorticoid properties, or administration of a CR11 receptor antagonist, will reverse and/or prevent these receptor changes. Aim 4 will investigate whether maternal deprivation in rats makes the brain more vulnerable to these receptor changes in adulthood.We will use in situ hybridization, radioimmunocytochemistry, and receptor autoradiography to quantify: 5HT1a and 5HT2a receptors, 5HT transporter, Glucocorticoid and Mineralocorticoid receptors, Corticotropin releasing hormone (CRH), CRH receptors, and CRH binding protein. This proposal brings together molecular/neuroanatomical tools, to increase our knowledge of the link between stress and depression. It is hoped that these series of 'preclinical' animal studies will help increase our understanding of the pathophysiological consequences of chronic stress, will help clarify the role of elevated corticosteroids in depression, and will give us someclues about how to treat, or prevent, the cumulative effect of hypercortisolemia in brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUDDEN HEARING LOSS MULTICENTER TREATMENT TRIAL Principal Investigator & Institution: Rauch, Steven D.; Associate Massachusetts Eye and Ear Infirmary 243 Charles St Boston, Ma 02114
Professor;
Timing: Fiscal Year 2004; Project Start 17-JUN-2004; Project End 31-MAY-2009 Summary: (provided by applicant): The overall objective of this project is to compare the efficacy of two different treatments for idiopathic sudden sensorineural hearing loss (SSNHL). SSNHL is an otologic emergency causing unilateral deafness of variable severity. If treated promptly with a short course of oral corticosteroids, approximately
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60% of patients regain some hearing. However, in patients with severe-to-profound SSNHL it is rare to fully recover hearing. Increasing duration of oral steroid therapy beyond three to four weeks has never been shown to improve hearing outcome, and the risk of steroid side effects rises with greater duration of treatment. Recent animal studies of corticosteroid penetrance into the inner ear and reports of treatment outcome in several small uncontrolled series of SSNHL patients suggest that local administration of corticosteroids by intratympanic (IT) injection may achieve equivalent or better hearing recovery while lowering the potential risk of systemic side effects. In this project we propose a multicenter prospective randomized clinical trial to compare the efficacy of oral prednisone vs. IT methylprednisolone for primary treatment of SSNHL. All qualified subjects will be randomized to receive either two weeks or oral prednisone or two weeks of IT methylprednisolone injections. The two Specific Aims of the study are to: (1) test the primary hypothesis that IT corticosteroids are as effective as oral prednisone for primary SSNHL treatment; and (2) compare the side-effects and adverse events in subjects treated with oral or IT steroids. The project is designed as an equivalency study. If the primary hypothesis of equivalency is supported, results of the second Specific Aim, comparison of side-effects, will guide clinical practice. If the two treatments are not equivalent, the study design enables us to detect which is better and by how much. Thus the results of this study will have significant impact on evidencebased clinical practice guidelines for management of SSNHL. This application is for the collaborating Clinical Coordinating Center (CCC). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE PHARMACOGENETICS OF ASTHMA TREATMENT Principal Investigator & Institution: Weiss, Scott T.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from investigator's abstract): Asthma is a chronic inflammatory syndrome of the airways which afflicts over 12 million people in the USA. It is characterized physiologically by recurrent airway obstruction which resolves spontaneously or as a result of treatment, Its etiology remains unknown. Despite the lack of understanding of is etiology, there are effective treatment for asthma. There are three main classes of asthma treatment in use today, inhaled B-agonists, inhaled corticosteroids and leukotriene modifiers; a given patient may use one, two or all of these types of treatments. The treatments are not uniformly effective; they vary in their efficacy amongst individuals and there are compelling preliminary data (outlined herein) suggesting that at least half of the variance in the treatment response may be genetic in origin; our proposal is structured to identify the genes responsible for this variable response. Our proposed approach is straightforward. For each of the three major asthma treatment pathways, we will: 1)Define a panel of target genes which are likely to modify the function of the pathway; 2) Scan these targets for DNA sequence variants; 3) As variants are identified they will ascertain which, if any, alter either the level of expression of function of their encoded proteins; 4) Genotype, at loci associated with functional implications in vitro, will be ascertained in asthma patients, who have been (existing patient resources) or will be (to be acquired patient resources) phenotyped with respect to the response to treatment with the class of asthma medication of interest;5) The investigators will use a case -control association approach to define specific genotypes associated with either a salutary treatment response or lack thereof. (In newly acquired populations they will use transmission disequilibrium testing); 6) Once genotypes associated with potential pharmacogentic predictive value
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are defined they will collaborate with the NIH sponsored Asthma Clinical Research Network to study patients with specific genotypes to determine if they provide predictive information about treatment responses; 7) Our approach will allow us to ascertain the pharmacogenetic basis for the observed variability in asthma treatment responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THYMOSIN BETA 4 AND AUTOIMMUNE OCULAR SURFACE DISEASE Principal Investigator & Institution: Sosne, Gabriel; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Keratoconjunctitivitis sicca (KCS), or dry eye disease, is one of the most common conditions seen by ophthalmologists and affects 15% of those from 65-84 years of age, or 4.3 million Americans. The pathophysiology of dry eye includes immune-mediated inflammation involving both the ocular surface and the lacrimal gland. While knowledge of the pathology of dry eye disease has improved significantly during recent years, the mainstay of treatment, ocular lubrication, provides only palliative relief at best to patients with severe dry eye disease. Therefore, attention has turned to immunomodulation as a therapeutic approach for I severe dry eye disease, especially for that seen in autoimmune diseases like Sjogren's syndrome, I rheumatoid arthritis, and systemic lupus erythematosus (SLE). Available agents such as corticosteroids have I considerable side effects that render them therapeutically impotent in a number of patients. Recently, the FDA approved Cyclosporine A (CSA), 0.5% (Restasis) for the treatment of moderate to severe dry eye. However, 85% of CSAtreated patients did not experience a significant increase in tear production. Therefore, a therapeutic agent that could reliably decrease immune-mediated ocular surface damage without significant adverse effects in a large proportion of affected patients would constitute a major therapeutic advance, particularly for dry eye disease. Thymosin beta 4 (Tb4) promotes corneal wound healing and reduces inflammation in mice after chemical injury to the eye. Since Tb4 has both anti-inflammatory and wound healing properties, it is an ideal candidate for evaluation in an autoimmune model of dry eye. Two specific aims are proposed to test the overall hypothesis of this application that Tb4 modulates lacrimal gland, corneal and conjunctival inflammation in an animal model of autoimmune dry eye disease. 1) To test the hypothesis that Tb4 alters production of cytokines, chemokines and specific matrix metalloproteinases (MMPs) in a murine model of Sjogren's syndrome; 2) To test the hypothesis that Tb4 alters autoimmune ocular surface damage in the MRL/Ipr mouse by decreasing lacrimal gland inflammation and conjunctival squamous metaplasia. By identifying Tb4 as a novel wound healing and anti-inflammatory agent to protect the ocular surface from inflammatory and immune tissue injury, it is aimed to substantiate the potential clinical usage of Tb4 for the majority of patients who are not relieved by currently available therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: URINE SURVEILLANCE
MRNA
PROFILING
FOR
RENAL
ALLOGRAFT
Principal Investigator & Institution: Suthanthiran, Manikkam; Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021
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Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: The overall objective of this project is to develop a noninvasive diagnostic test that is predictive, diagnostic and prognostic of human renal allograft rejection. In an exploratory study, we found that the levels of expression of mRNA encoding cytotoxic proteins perforin and granzyme B in urinary cells of renal allograft recipients are diagnostic of acute rejection of human renal allografts. We now propose to further develop and refine the noninvasive diagnosis of acute rejection. The specific aims of this investigation are: Specific aim 1. To test the hypothesis that mRNA profiling of urinary cells is diagnostic of subclinical rejection. We will measure mRNA for perforin, granzyme B, fas ligand, CD3 epsilon chain (CD3), interferon gamma (IFN-gamma), and interleukin-15 (IL-15) in urine specimens obtained at the time of protocol biopsies and determine the sensitivity and specificity of mRNA levels in diagnosing subclinical rejection. Specific aim 2. To test the hypotheses that: a) alterations in mRNA levels in sequential urine specimens predict the development of acute rejection, and b) mRNA profiles predict renal allograft function. We will determine whether acute rejection episodes can be predicted by alterations in mRNA levels measured in sequential urine specimens. In addition to mRNAs listed under Specific Aim 1, we will measure level of expression of mRNA for Bcl-2, A20, hemeoxygenase-1 (HO1), Bax, and transforming growth factor-beta1 (TGF-beta1) in urinary cells and test the hypothesis that the mRNA levels predict renal allograft function. Specific aim 3. To investigate whether mRNA profiles of urinary cells are diagnostic of clinical acute rejection and to determine whether mRNA profiles are prognostic with respect to responsiveness to antirejection therapy with corticosteroids, and in identifying allografts at risk for progressive decline in renal function. We will determine whether the level of expression of mRNA for granzyme B, perforin, and CD3, IFN-gamma and IL-15 are diagnostic of clinical acute rejection and are higher in those with corticosteroid resistant acute rejections compared to corticosteroid sensitive acute rejections. We will also determine whether hyperexpression of mRNA for cytotoxic proteins and for Bax and TGF-beta1 is associated with graft functional decline whereas lack of hyperexpression of mRNA for cytotoxic proteins, Bax and TGF-beta1 and hyperexpression of mRNA for Bcl-2, A20 and HO1 is associated with stable renal function. 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 “corticosteroids” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for corticosteroids in the PubMed Central database:
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Alpha-Aminoisobutyric Acid Transport in Human Leukemic Lymphocytes: In Vitro Characteristics and Inhibition by Cortisol and Cycloheximide. by Baran DT, Lichtman MA, Peck WA.; 1972 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292375
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Cell contacts are required for induction by cortisol of glutamine synthetase gene transcription in the retina. by Vardimon L, Fox LL, Degenstein L, Moscona AA.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281889
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Circadian secretion of cortisol in bipolar disorder. by Cervantes P, Gelber S, Kin F, Nair VN, Schwartz G.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=167199
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Comparison of Corticosteroids for Treatment of Respiratory Syncytial Virus Bronchiolitis and Pneumonia in Cotton Rats. by Ottolini MG, Curtis SJ, Porter DD, Mathews A, Richardson JY, Hemming VG, Prince GA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127305
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Differential and Integral Corticosteroid Feedback Effects on ACTH Secretion in Hypoadrenocorticism. by Fehm HL, Voigt KH, Kummer G, Lang R, Pfeiffer EF.; 1979 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371946
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Effect of cortisol on the growth of Chlamydia trachomatis in McCoy cells. by Bushell AC, Hobson D.; 1978 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=422088
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Effects of ciprofloxacin on testosterone and cortisol concentrations in healthy males. by Waite NM, Edwards DJ, Arnott WS, Warbasse LH.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172780
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Effects of cloned interferon alpha 2 in normal volunteers: febrile reactions and changes in circulating corticosteroids and trace metals. by Scott GM, Ward RJ, Wright DJ, Robinson JA, Onwubalili JK, Gauci CL.; 1983 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184706
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Effects of corticosteroids and cyclophosphamide on a mouse model of Chlamydia trachomatis pneumonitis. by Stephens RS, Chen WJ, Kuo CC.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351095
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Effects of Corticosteroids and Splenectomy on the Immune Clearance and Destruction of Erythrocytes. by Atkinson JP, Schreiber AD, Frank MM.; 1973 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302416
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Effects of Corticosteroids on Eosinophil Chemotaxis and Adherence. by Altman LC, Hill JS, Hairfield WM, Mullarkey MF.; 1981 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371568
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Effects of Corticosteroids on Human Monocyte Function. by Rinehart JJ, Balcerzak SP, Sagone AL, LoBuglio AF.; 1974 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301688
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Evidence for Different Gestation-Dependent Effects of Cortisol on Cultured Fetal Lung Cells. by Smith BT, Torday JS, Giroud CJ.; 1974 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302647
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Evidence for Induction by Cortisol In Vitro of a Protein Inhibitor of Transport and Phosphorylation Processes in Rat Thymocytes. by Makman MH, Dvorkin B, White A.; 1971 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=389169
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Expression of biologically active human corticosteroid binding globulin by insect cells: acquisition of function requires glycosylation and transport. by Ghose-Dastidar J, Ross JB, Green R.; 1991 Aug 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52094
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Formation of covalent adducts between cortisol and 16 alpha-hydroxyestrone and protein: possible role in the pathogenesis of cortisol toxicity and systemic lupus erythematosus. by Bucala R, Fishman J, Cerami A.; 1982 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346407
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Income-based drug benefit policy: impact on receipt of inhaled corticosteroid prescriptions by Manitoba children with asthma. by Kozyrskyj AL, Mustard CA, Cheang MS, Simons FE.; 2001 Oct 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81497
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Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. by Weiner JM, Abramson MJ, Puy RM.; 1998 Dec 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28740
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Parotid Fluid Cortisol and Cortisone. by Katz FH, Shannon IL.; 1969 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322292
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Perception of bronchial obstruction in asthmatic patients. Relationship with bronchial eosinophilic inflammation and epithelial damage and effect of corticosteroid treatment. by Roisman GL, Peiffer C, Lacronique JG, Le Cae A, Dusser DJ.; 1995 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185167
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Positive Rate-Sensitive Corticosteroid Feedback Mechanism of ACTH Secretion in Cushing's Disease. by Fehm HL, Voigt KH, Kummer G, Pfeiffer EF.; 1979 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372095
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Primary cortisol resistance in man. A glucocorticoid receptor-mediated disease. by Chrousos GP, Vingerhoeds A, Brandon D, Eil C, Pugeat M, DeVroede M, Loriaux DL, Lipsett MB.; 1982 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370198
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Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema. by Thomas KS, Armstrong S, Avery A, Po AL, O'Neill C, Young S, Williams HC.; 2002 Mar 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100318
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Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration. by Libby P, Maroko PR, Bloor CM, Sobel BE, Braunwald E.; 1973 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302298
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Synergistic Interactions of Physiologic Increments of Glucagon, Epinephrine, and Cortisol in the Dog A MODEL FOR STRESS-INDUCED HYPERGLYCEMIA. by Eigler N, Sacca L, Sherwin RS.; 1979 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=371925
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Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma. by Brocklebank D, Wright J, Cates C.; 2001 Oct 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58536
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The Effects of Estradiol and Estriol on Plasma Levels of Cortisol and Thyroid Hormone-Binding Globulins and on Aldosterone and Cortisol Secretion Rates in Man. by Katz FH, Kappas A.; 1967 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=292927
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Treatment of shoulder complaints in general practice: long term results of a randomised, single blind study comparing physiotherapy, manipulation, and corticosteroid injection. by Winters JC, Jorritsma W, Groenier KH, Sobel JS, Jong BM, Arendzen HJ.; 1999 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27885
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Tsp509I polymorphism in exon 2 of the glucocorticoid receptor gene in relation to obesity and cortisol secretion: cohort study. by Rosmond R, Bouchard C, Bjorntorp P.; 2001 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26546
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 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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The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with corticosteroids, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “corticosteroids” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for corticosteroids (hyperlinks lead to article summaries): •
A population based case-control study of cataract and inhaled corticosteroids. Author(s): Smeeth L, Boulis M, Hubbard R, Fletcher AE. Source: The British Journal of Ophthalmology. 2003 October; 87(10): 1247-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507760
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A randomized comparative study of short term response to blind injection versus sonographic-guided injection of local corticosteroids in patients with painful shoulder. Author(s): Naredo E, Cabero F, Beneyto P, Cruz A, Mondejar B, Uson J, Palop MJ, Crespo M. Source: The Journal of Rheumatology. 2004 February; 31(2): 308-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760802
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A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy. Author(s): Yost NP, McIntire DD, Wians FH Jr, Ramin SM, Balko JA, Leveno KJ. Source: Obstetrics and Gynecology. 2003 December; 102(6): 1250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662211
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Acute neutrophilic meningitis treated successfully with corticosteroids. Author(s): Alexopoulou A, Deutsch M, Dourakis SP. Source: Southern Medical Journal. 2003 September; 96(9): 912-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513990
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Add-on effects of suplatast tosilate in bronchial asthma patients treated with inhaled corticosteroids. Author(s): Sano T, Nakamura Y, Yanagawa H, Bando H, Nii A, Yoshida S, Sone S; Higashishikoku Asthma Research Group. Source: Lung. 2003; 181(4): 227-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692563
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Adherence to montelukast versus inhaled corticosteroids in children with asthma. Author(s): Carter ER, Ananthakrishnan M. Source: Pediatric Pulmonology. 2003 October; 36(4): 301-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12950042
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Administration of corticosteroids for acute spinal cord injury: the current practice of trauma medical directors and emergency medical system physician advisors. Author(s): Peter Vellman W, Hawkes AP, Lammertse DP. Source: Spine. 2003 May 1; 28(9): 941-7; Discussion 947. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942012
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Adrenal insufficiency and diabetes mellitus secondary to the use of topical corticosteroids for cosmetic purpose. Author(s): Sobngwi E, Lubin V, Ury P, Timsit FJ, Gautier JF, Vexiau P. Source: Annales D'endocrinologie. 2003 June; 64(3): 202-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12910062
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Adrenal insufficiency from inhaled corticosteroids. Author(s): White A, Woodmansee DP. Source: Annals of Internal Medicine. 2004 March 16; 140(6): W27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023738
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Adverse events of standardized regimens of corticosteroids for prophylaxis and treatment of nerve function impairment in leprosy: results from the 'TRIPOD' trials. Author(s): Richardus JH, Withington SG, Anderson AM, Croft RP, Nicholls PG, Van Brakel WH, Smith WC. Source: Lepr Rev. 2003 December; 74(4): 319-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750577
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Airway responsiveness to adenosine 5'-monophosphate and exhaled nitric oxide measurements: predictive value as markers for reducing the dose of inhaled corticosteroids in asthmatic subjects. Author(s): Prieto L, Bruno L, Gutierrez V, Uixera S, Perez-Frances C, Lanuza A, Ferrer A. Source: Chest. 2003 October; 124(4): 1325-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555562
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Allergy to corticosteroids: update and review of epidemiology, clinical characteristics, and structural cross-reactivity. Author(s): Scheuer E, Warshaw E. Source: American Journal of Contact Dermatitis : Official Journal of the American Contact Dermatitis Society. 2003 December; 14(4): 179-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738718
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Antenatal corticosteroids for fetal maturation in women at risk for preterm delivery. Author(s): Vidaeff AC, Doyle NM, Gilstrap LC 3rd. Source: Clin Perinatol. 2003 December; 30(4): 825-40, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714924
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Antenatal corticosteroids: we continue to learn. Author(s): Wapner R. Source: American Journal of Obstetrics and Gynecology. 2004 April; 190(4): 875. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118604
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Anticonvulsant hypersensitivity syndrome: treatment with corticosteroids and intravenous immunoglobulin. Author(s): Mostella J, Pieroni R, Jones R, Finch CK. Source: Southern Medical Journal. 2004 March; 97(3): 319-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043348
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Assessment of information and education about topical corticosteroids in dermatology outpatient departments: experience from Turkey. Author(s): Basak PY, Ozturk M, Baysal V. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 November; 17(6): 652-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14761131
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Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study. Author(s): Selroos O, Lofroos AB, Pietinalho A, Riska H. Source: Respiratory Medicine. 2004 March; 98(3): 254-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15002762
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Asthma exacerbations and inhaled corticosteroids. Author(s): Masoli M, Beasley R. Source: Lancet. 2004 April 10; 363(9416): 1236. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081663
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Asthma exacerbations and inhaled corticosteroids. Author(s): Fardon T, Gray R, Lipworth B. Source: Lancet. 2004 April 10; 363(9416): 1235; Author Reply 1235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081662
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Asthma exacerbations and inhaled corticosteroids. Author(s): Lee DK. Source: Lancet. 2004 April 10; 363(9416): 1235; Author Reply 1235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081661
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Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia. Author(s): Bosanquet AG, Sturm I, Wieder T, Essmann F, Bosanquet MI, Head DJ, Dorken B, Daniel PT. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 June; 16(6): 1035-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12040435
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Behavioral effects of corticosteroids in steroid-sensitive nephrotic syndrome. Author(s): Soliday E, Grey S, Lande MB. Source: Pediatrics. 1999 October; 104(4): E51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10506276
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Benefits and risks of inhaled corticosteroids in chronic obstructive pulmonary disease. Author(s): Bonay M, Bancal C, Crestani B. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(1): 57-71. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11820912
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Benefits of low-dose corticosteroids in rheumatoid arthritis. Author(s): Cohen MD, Conn DL. Source: Bulletin on the Rheumatic Diseases. 1997 June; 46(4): 4-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9188203
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Bilateral femoral avascular necrosis in a man with psoriasis: responsibility of topical corticosteroids and role of cyclosporine. Author(s): Reichert-Penetrat S, Trechot P, Barbaud A, Gillet P, Schmutz JL. Source: Dermatology (Basel, Switzerland). 2001; 203(4): 356-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11752834
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Bilateral percutaneous balloon angioplasty of the axillary arteries in a patient with giant cell arteritis and upper extremity ischemic symptoms not responsive to corticosteroids. Author(s): Dellaripa PF, Eisenhauer AC. Source: The Journal of Rheumatology. 1998 July; 25(7): 1429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676780
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Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Author(s): Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D, Diav-Citrin O, Chitayat D, Nulman I, Einarson TR, Koren G. Source: Teratology. 2000 December; 62(6): 385-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11091360
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Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids. Author(s): Taieb J, Mathurin P, Elbim C, Cluzel P, Arce-Vicioso M, Bernard B, Opolon P, Gougerot-Pocidalo MA, Poynard T, Chollet-Martin S. Source: Journal of Hepatology. 2000 April; 32(4): 579-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10782906
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Bone density in asthmatic children treated with inhaled corticosteroids. Author(s): Reilly SM, Hambleton G, Adams JE, Mughal MZ. Source: Archives of Disease in Childhood. 2001 February; 84(2): 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11159303
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Bone mineral density and body composition and influencing factors in children with rheumatic diseases treated with corticosteroids. Author(s): Mul D, van Suijlekom-Smit LW, ten Cate R, Bekkering WP, de Muinck Keizer-Schrama SM. Source: J Pediatr Endocrinol Metab. 2002 February; 15(2): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11878272
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Bone mineral density and bone metabolism of prepubertal children with asthma after long-term treatment with inhaled corticosteroids. Author(s): Boot AM, de Jongste JC, Verberne AA, Pols HA, de Muinck Keizer-Schrama SM. Source: Pediatric Pulmonology. 1997 December; 24(6): 379-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9448228
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Bone mineral density in asthmatic patients treated with inhaled corticosteroids: a case-control study. Author(s): Luengo M, del Rio L, Pons F, Picado C. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1997 September; 10(9): 2110-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9311512
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Bone mineral density in subjects with mild asthma randomised to treatment with inhaled corticosteroids or non-corticosteroid treatment for two years. Author(s): Tattersfield AE, Town GI, Johnell O, Picado C, Aubier M, Braillon P, Karlstrom R. Source: Thorax. 2001 April; 56(4): 272-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11254817
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Bone status in multiple sclerosis: beyond corticosteroids. Author(s): Tuzun S, Altintas A, Karacan I, Tangurek S, Saip S, Siva A. Source: Multiple Sclerosis (Houndmills, Basingstoke, England). 2003 December; 9(6): 600-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14664473
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Bronchoalveolar lavage cellular profiles in lung transplantation: the effect of inhaled corticosteroids. Author(s): Whitford H, Orsida B, Kotsimbos T, Pais M, Ward C, Zheng L, Williams T, Walters EH, Snell G. Source: Ann Transplant. 2000; 5(3): 31-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11147027
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Budesonide/formoterol in a single inhaler versus inhaled corticosteroids alone in the treatment of asthma. Author(s): Tal A, Simon G, Vermeulen JH, Petru V, Cobos N, Everard ML, de Boeck K. Source: Pediatric Pulmonology. 2002 November; 34(5): 342-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357478
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Bullous pemphigoid in an HB virus carrier: interaction between corticosteroids and HB virus. Author(s): Inadomi T, Saito T, Kaneko M, Hashimoto T, Suzuki H. Source: The Journal of Dermatology. 1997 March; 24(3): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9114616
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Burden of corticosteroids in children with asthma in primary care: retrospective observational study. Author(s): Ekins-Daukes S, Simpson CR, Helms PJ, Taylor MW, McLay JS. Source: Bmj (Clinical Research Ed.). 2002 June 8; 324(7350): 1374. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052808
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Cardiac consequences of the systemic lupus erythematosus therapy with corticosteroids morphological study. Author(s): Arsenescu C, Butcovan D, Rotar M, Georgescu GI. Source: Rev Med Chir Soc Med Nat Iasi. 2002 October-December; 106(4): 812-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14974235
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Chronic eosinophilic pneumonia: treatment with inhaled corticosteroids. Author(s): Minakuchi M, Niimi A, Matsumoto H, Amitani R, Mishima M. Source: Respiration; International Review of Thoracic Diseases. 2003 July-August; 70(4): 362-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512670
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Circadian and ultradian (12 h) variations of skin blood flow and barrier function in non-irritated and irritated skin-effect of topical corticosteroids. Author(s): Yosipovitch G, Sackett-Lundeen L, Goon A, Yiong Huak C, Leok Goh C, Haus E. Source: The Journal of Investigative Dermatology. 2004 March; 122(3): 824-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086571
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Clinical characteristics of 195 Japanese sarcoidosis patients treated with oral corticosteroids. Author(s): Sugisaki K, Yamaguchi T, Nagai S, Ohmiti M, Takenaka S, Morimoto S, Ishihara M, Tachibana T, Tsuda T. Source: Sarcoidosis Vasc Diffuse Lung Dis. 2003 October; 20(3): 222-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620165
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Comparison of combination inhalers vs inhaled corticosteroids alone in moderate persistent asthma. Author(s): Lee DK, Jackson CM, Currie GP, Cockburn WJ, Lipworth BJ. Source: British Journal of Clinical Pharmacology. 2003 November; 56(5): 494-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651722
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Corticosteroids and inhaled salbutamol in patients with reversible airway obstruction markedly decrease the incidence of bronchospasm after tracheal intubation. Author(s): Silvanus MT, Groeben H, Peters J. Source: Anesthesiology. 2004 May; 100(5): 1052-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114199
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Corticosteroids and lamivudine combined to treat acute severe flare-up in a chronic hepatitis B and C patient. Author(s): Kanda T, Yokosuka O, Imazeki F, Yoshida S, Suzuki Y, Nagao K, Saisho H. Source: Journal of Gastroenterology and Hepatology. 2004 February; 19(2): 238-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14731142
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Corticosteroids as adjunctive treatment in Austrian's syndrome (pneumococcal endocarditis, meningitis, and pneumonia): report of two cases and review of the literature. Author(s): du Cheyron D, Lesage A, Le Page O, Flais F, Leclercq R, Charbonneau P. Source: Journal of Clinical Pathology. 2003 November; 56(11): 879-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14600140
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Corticosteroids for first-time young wheezers: current status of the controversy. Author(s): Weinberger M. Source: The Journal of Pediatrics. 2003 December; 143(6): 700-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657809
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Corticosteroids for HELLP syndrome in pregnancy. Author(s): Matchaba P, Moodley J. Source: Cochrane Database Syst Rev. 2004; (1): Cd002076. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14973983
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Corticosteroids for maintenance of remission in Crohn's disease. Author(s): Steinhart AH, Ewe K, Griffiths AM, Modigliani R, Thomsen OO. Source: Cochrane Database Syst Rev. 2003; (4): Cd000301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583917
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Corticosteroids for supraglottitis. Author(s): Phillips JS, Innes AJ, Naik MS. Source: British Journal of Anaesthesia. 2004 March; 92(3): 454-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970144
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Corticosteroids for treating severe sepsis and septic shock. Author(s): Annane D, Bellissant E, Bollaert PE, Briegel J, Keh D, Kupfer Y. Source: Cochrane Database Syst Rev. 2004; (1): Cd002243. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14973984
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Corticosteroids in acute asthma: past, present, and future. Author(s): Scarfone RJ, Friedlaender E. Source: Pediatric Emergency Care. 2003 October; 19(5): 355-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578839
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Corticosteroids in the treatment of thrombotic thrombocytopenic purpura. Author(s): Ozsoylu S. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 October; 92(10): 1229; Author Reply 1229. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632348
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Corticosteroids underemployment in delayed chemotherapy-induced nausea and emesis with poor adherence to American Society of Clinical Oncology guidelines: is this a reasonable clinical choice for the elderly? Author(s): Gridelli C, Maione P, Rossi A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 November 1; 21(21): 4066-7; Author Reply 4067-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581432
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Corticosteroids, central serous chorioretinopathy, and neurocysticercosis. Author(s): Bowie EM, Folk JC, Barnes CH. Source: Archives of Ophthalmology. 2004 February; 122(2): 281-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769610
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Corticosteroids--from an idea to clinical use. Author(s): Lundberg IE, Grundtman C, Larsson E, Klareskog L. Source: Best Practice & Research. Clinical Rheumatology. 2004 February; 18(1): 7-19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123034
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Cost-effectiveness of inhaled corticosteroids for chronic obstructive pulmonary disease according to disease severity. Author(s): Sin DD, Golmohammadi K, Jacobs P. Source: The American Journal of Medicine. 2004 March 1; 116(5): 325-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984818
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Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole. Author(s): Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN. Source: The Annals of Pharmacotherapy. 2004 January; 38(1): 46-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742792
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Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants. Author(s): Halliday HL, Ehrenkranz RA, Doyle LW. Source: Cochrane Database Syst Rev. 2003; (1): Cd001145. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535401
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Deposition and effects of inhaled corticosteroids. Author(s): Newman SP. Source: Clinical Pharmacokinetics. 2003; 42(6): 529-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12793838
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Determination of natural corticosteroids in urine samples from sportsmen. Author(s): Rivero-Marabe JJ, Maynar-Marino JI, Garcia-de-Tiedra MP, Galan-Martin AM, Caballero-Loscos MJ, Maynar-Marino M. Source: J Chromatogr B Biomed Sci Appl. 2001 September 15; 761(1): 77-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11585134
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Developmental assessment of prematurely born children exposed to antenatal corticosteroids. Author(s): Arad I, Bromiker R. Source: Isr Med Assoc J. 2003 September; 5(9): 659-61. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509158
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Differential efficacy of corticosteroids and interferon in a patient with chronic hepatitis C-autoimmune hepatitis overlap syndrome. Author(s): Petersen-Benz C, Kasper HU, Dries V, Goeser T. Source: Clin Gastroenterol Hepatol. 2004 May; 2(5): 440-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118984
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Differential prescribing of inhaled corticosteroids in New Zealand general practice. Author(s): Hall J, Penrose A, Tomlin A, Reid J. Source: N Z Med J. 2003 August 22; 116(1180): U563. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581985
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Disparate results in studies of methotrexate plus corticosteroids in the treatment of giant cell arteritis: comment on the article by Hoffman et al. Author(s): Jover JA, Hernandez-Garcia C, Morado IC, Vargas E, Banares A, FernandezGutierrez B. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1158-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687561
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Do inhaled corticosteroids affect perception of dyspnea during bronchoconstriction in asthma? Author(s): Ottanelli R, Rosi E, Romagnoli I, Grazzini M, Stendardi L, Duranti R, Scano G. Source: Chest. 2001 September; 120(3): 770-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555508
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Do inhaled corticosteroids slow FEV1 decline in COPD after all? Author(s): Duerden MG. Source: Thorax. 2004 June; 59(6): 538-9; Author Reply 539-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15170045
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Do intranasal corticosteroids aid treatment of acute sinusitis in patients with a history of recurrent sinus symptoms? Author(s): Winn RJ. Source: The Journal of Family Practice. 2002 April; 51(4): 386. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978269
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Do systemic corticosteroids lessen symptoms in acute exacerbations of COPD? Author(s): McDiarmid T, Mackler L, McDiarmuid T. Source: The Journal of Family Practice. 2003 December; 52(12): 979-80. Erratum In: J Fam Pract. 2004 February; 53(2): 137. Mcdiarmuid Todd [corrected to Mcdiarmid Todd]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653988
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Does the combined antenatal use of corticosteroids and antibiotics increase late-onset neonatal sepsis in the very low birth weight infant? Author(s): How HY, Sutler D, Khoury JC, Donovan EF, Siddiqi TA, Spinnato JA. Source: American Journal of Obstetrics and Gynecology. 2001 November; 185(5): 1081-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717637
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Dose equivalency evaluation of major corticosteroids: pharmacokinetics and cell trafficking and cortisol dynamics. Author(s): Mager DE, Lin SX, Blum RA, Lates CD, Jusko WJ. Source: Journal of Clinical Pharmacology. 2003 November; 43(11): 1216-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551176
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Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma. Author(s): Kanniess F, Richter K, Janicki S, Schleiss MB, Jorres RA, Magnussen H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 November; 20(5): 1080-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12449158
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Dose response and therapeutic index of inhaled corticosteroids in asthma. Author(s): Hogger P. Source: Current Opinion in Pulmonary Medicine. 2003 January; 9(1): 1-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12476077
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Dose response of inhaled corticosteroids on bronchial hyperresponsiveness: a metaanalysis. Author(s): Currie GP, Fowler SJ, Lipworth BJ. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 February; 90(2): 194-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602665
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Dose-dependent effects of corticosteroids on the expression of matrix-related genes in normal and cytokine-treated articular chondrocytes. Author(s): Richardson DW, Dodge GR. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2003 January; 52(1): 39-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608648
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Down-regulation of the aberrant expression of the inflammation mediator high mobility group box chromosomal protein 1 in muscle tissue of patients with polymyositis and dermatomyositis treated with corticosteroids. Author(s): Ulfgren AK, Grundtman C, Borg K, Alexanderson H, Andersson U, Harris HE, Lundberg IE. Source: Arthritis and Rheumatism. 2004 May; 50(5): 1586-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15146429
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Dual components of optimal asthma therapy: scientific and clinical rationale for the use of long-acting beta-agonists with inhaled corticosteroids. Author(s): Naedele-Risha R, Dorinsky P, Craig TJ. Source: J Am Osteopath Assoc. 2001 September; 101(9): 526-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575039
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Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Author(s): Edmonds ML, Camargo CA Jr, Pollack CV Jr, Rowe BH. Source: Cochrane Database Syst Rev. 2003; (3): Cd002308. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917930
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Effect of corticosteroids in addition to intravenous gamma globulin therapy on serum cytokine levels in the acute phase of Kawasaki disease in children. Author(s): Okada Y, Shinohara M, Kobayashi T, Inoue Y, Tomomasa T, Kobayashi T, Morikawa A; Gunma Kawasaki Disease Study Group. Source: The Journal of Pediatrics. 2003 September; 143(3): 363-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517521
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Effect of inhaled corticosteroids on markers of pulmonary inflammation and lung maturation in preterm infants with evolving chronic lung disease. Author(s): Parikh NA, Locke RG, Chidekel A, Leef KH, Emberger J, Paul DA, Stefano JL. Source: J Am Osteopath Assoc. 2004 March; 104(3): 114-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15083986
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Effect of lamotrigine on mood and cognition in patients receiving chronic exogenous corticosteroids. Author(s): Brown ES, Frol A, Bobadilla L, Nejtek VA, Perantie DC, Dhillon H. Source: Psychosomatics. 2003 May-June; 44(3): 204-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724501
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Effect of octreotide and corticosteroids on human sphincter of oddi motility. Author(s): Viazis N, Rekoumis G, Vlachogiannakos J, Avgerinos A. Source: Journal of Gastroenterology and Hepatology. 2004 January; 19(1): 116-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675256
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Effect of rocaltrol on bone mass in patients with pulmonary disease treated with corticosteroids. Author(s): Mirzaei S, Zajicek HK, Knoll P, Hahn M, Levi M, Kohn H, Pohl W. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 2003 May; 40(3): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807168
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Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis. Author(s): Kakumanu SS, Mende CN, Lehman EB, Hughes K, Craig TJ. Source: J Am Osteopath Assoc. 2003 September; 103(9): 423-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527077
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Effectiveness of inhaled corticosteroids in chronic obstructive pulmonary disease: immortal time bias in observational studies. Author(s): Suissa S. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 1; 168(1): 49-53. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663327
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Effects of a single course of corticosteroids given more than 7 days before birth: a systematic review. Author(s): McLaughlin KJ, Crowther CA, Walker N, Harding JE. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2003 April; 43(2): 101-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14712961
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Effects of inhaled corticosteroids with different lung deposition on exhaled hydrogen peroxide in stable COPD patients. Author(s): van Beurden WJ, Harff GA, Dekhuijzen PN, van der Poel-Smet SM, Smeenk FW. Source: Respiration; International Review of Thoracic Diseases. 2003 May-June; 70(3): 242-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915742
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Effects of inhaled corticosteroids, leukotriene receptor antagonists, or both, plus longacting beta2-agonists on asthma pathophysiology: a review of the evidence. Author(s): Vignola AM. Source: Drugs. 2003; 63 Suppl 2: 35-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984079
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Effects of phenobarbital and multiple-dose corticosteroids on developmental outcome at age 7 years. Author(s): Thorp JA, O'Connor M, Belden B, Etzenhouser J, Hoffman EL, Jones PG. Source: Obstetrics and Gynecology. 2003 February; 101(2): 363-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12576262
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Effects of prescription corticosteroids on mood and memory. Author(s): Hukovic N, Brown ES. Source: Adv Psychosom Med. 2003; 24: 161-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584353
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Efficacy of corticosteroids and cyclosporin in the treatment of retinal vasculitis in patients with Behcet's disease. Author(s): Ermakova NA. Source: Advances in Experimental Medicine and Biology. 2003; 528: 563-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12918765
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Efficacy of corticosteroids in sarcoidosis presenting with atrioventricular block. Author(s): Kato Y, Morimoto S, Uemura A, Hiramitsu S, Ito T, Hishida H. Source: Sarcoidosis Vasc Diffuse Lung Dis. 2003 June; 20(2): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12870723
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Efficiency of colchicine and corticosteroids in a leg ulceration with cholesterol embolism in a woman with rheumatoid arthritis. Author(s): Verneuil L, Ze Bekolo R, Dompmartin A, Comoz F, Marcelli C, Leroy D. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 1014-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869676
Studies
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Eformoterol Turbohaler compared with salmeterol by dry powder inhaler in asthmatic children not controlled on inhaled corticosteroids. Author(s): Everden P, Campbell M, Harnden C, McGoldrick H, Bodalia B, Manion V, Reynia S; FACT study group. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2004 February; 15(1): 40-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998381
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Evaluation of montelukast in 8 to 14 year old children with mild persistent asthma and compared with inhaled corticosteroids. Author(s): Karaman O, Sunneli L, Uzuner N, Islekel H, Turgut CS, Kose S, Tezcan D, Coker C, Erbayraktar Z. Source: Allergologia Et Immunopathologia. 2004 January-February; 32(1): 21-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980192
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Exophthalmos: a rare complication of systemic corticosteroids. Author(s): Lobrano A, Pierce P, Harkins K. Source: J Miss State Med Assoc. 2002 April; 43(4): 112. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11989195
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Extra-adrenal production of corticosteroids. Author(s): Davies E, MacKenzie SM. Source: Clinical and Experimental Pharmacology & Physiology. 2003 July; 30(7): 437-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823256
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Failure of inhaled corticosteroids to improve small airway obstruction in two patients with sarcoidosis. Author(s): Herer B. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(1): 107-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844975
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Familial pattern of corticosteroids and their metabolism in adult human subjects--the Scottish Adult Twin Study. Author(s): Inglis GC, Ingram MC, Holloway CD, Swan L, Birnie D, Hillis WS, Davies E, Fraser R, Connell JM. Source: The Journal of Clinical Endocrinology and Metabolism. 1999 November; 84(11): 4132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10566661
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Fatal aspergillosis in a patient with SARS who was treated with corticosteroids. Author(s): Wang H, Ding Y, Li X, Yang L, Zhang W, Kang W. Source: The New England Journal of Medicine. 2003 July 31; 349(5): 507-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890854
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Fetal exposure to corticosteroids: how low can we go? Author(s): Nijland MJ. Source: The Journal of Physiology. 2003 May 15; 549(Pt 1): 1. Epub 2003 March 28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665601
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Fibrotic scar formation in central serous chorioretinopathy developed during systemic treatment with corticosteroids. Author(s): Hooymans JM. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1998 November; 236(11): 876-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825265
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Finer points about intravitreal corticosteroids. Author(s): Vedantham V. Source: Indian J Ophthalmol. 2003 September; 51(3): 285; Author Reply 285-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14601865
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First treatment with inhaled corticosteroids and the prevention of admissions to hospital for asthma. Author(s): Blais L, Suissa S, Boivin JF, Ernst P. Source: Thorax. 1998 December; 53(12): 1025-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10195073
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Fluorescence derivatisation of urinary corticosteroids for high-performance liquid chromatographic analysis. Author(s): Neufeld E, Chayen R, Stern N. Source: J Chromatogr B Biomed Sci Appl. 1998 November 6; 718(2): 273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840438
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Fluorinated ocular/periocular corticosteroids have caused death as well as glaucoma in children. Author(s): Romano PE. Source: Clinical & Experimental Ophthalmology. 2003 June; 31(3): 279-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786788
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Fluorodeoxyglucose PET scan in pulmonary sarcoidosis during treatment with inhaled and oral corticosteroids. Author(s): Milman N, Mortensen J, Sloth C. Source: Respiration; International Review of Thoracic Diseases. 2003 July-August; 70(4): 408-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14512678
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Formoterol (Foradil) and medium-high doses of inhaled corticosteroids are more effective than high doses of corticosteroids in moderate-to-severe asthma. Author(s): Mitchell C, Jenkins C, Scicchitano R, Rubinfeld A, Kottakis J. Source: Pulmonary Pharmacology & Therapeutics. 2003; 16(5): 299-306. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877821
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Formoterol used as needed improves health-related quality of life in asthmatic patients uncontrolled with inhaled corticosteroids. Author(s): Stahl E, Postma DS, Svensson K, Tattersfield AE, Eivindson A, Schreurs A, Lofdahl CG. Source: Respiratory Medicine. 2003 September; 97(9): 1061-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509561
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Frequency of application of topical corticosteroids: an overview. Author(s): Lagos BR, Maibach HI. Source: The British Journal of Dermatology. 1998 November; 139(5): 763-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9892939
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From mega to more reasonable doses of corticosteroids: a decade to recreate hope. Author(s): Carlet J. Source: Critical Care Medicine. 1999 April; 27(4): 672-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10321643
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Gestational diabetes mellitus in women receiving beta-adrenergics and corticosteroids for threatened preterm delivery. Author(s): Fisher JE, Smith RS, Lagrandeur R, Lorenz RP. Source: Obstetrics and Gynecology. 1997 December; 90(6): 880-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9397094
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Glaucoma from topical corticosteroids to the eyelids. Author(s): Garrott HM, Walland MJ. Source: Clinical & Experimental Ophthalmology. 2004 April; 32(2): 224-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068445
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Growth of asthmatic children before long-term treatment with inhaled corticosteroids. Author(s): Moudiou T, Theophilatou D, Priftis K, Papadimitriou A. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 2003 September; 40(6): 667-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579998
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Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 16. The use of corticosteroids in the treatment of severe pediatric traumatic brain injury. Author(s): Adelson PD, Bratton SL, Carney NA, Chesnut RM, du Coudray HE, Goldstein B, Kochanek PM, Miller HC, Partington MD, Selden NR, Warden CR, Wright DW; American Association for Surgery of Trauma; Child Neurology Society; International Society for Pediatric Neurosurgery; International Trauma Anesthesia and Critical Care Society; Society of Critical Care Medicine; World Federation of Pediatric Intensive and Critical Care Societies. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 July; 4(3 Suppl): S60-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847352
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HELLP syndrome and postpartum corticosteroids. Author(s): Varol F, Aydin T, Gucer F. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 May; 73(2): 157-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336737
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Hepatosplenic cat scratch disease treated with corticosteroids. Author(s): Bryant K, Marshall GS. Source: Archives of Disease in Childhood. 2003 April; 88(4): 345-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651767
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Herpes simplex virus encephalitis complicating myxedema coma treated with corticosteroids. Author(s): Doherty MJ, Baxter AB, Longstreth WT Jr. Source: Neurology. 2001 April 24; 56(8): 1114-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320194
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High constitutive glucocorticoid receptor beta in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids. Author(s): Strickland I, Kisich K, Hauk PJ, Vottero A, Chrousos GP, Klemm DJ, Leung DY. Source: The Journal of Experimental Medicine. 2001 March 5; 193(5): 585-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11238589
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High dose, alternate day corticosteroids for systemic onset juvenile rheumatoid arthritis. Author(s): Kimura Y, Fieldston E, Devries-Vandervlugt B, Li S, Imundo L. Source: The Journal of Rheumatology. 2000 August; 27(8): 2018-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10955346
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High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas. Author(s): Egbert JE, Paul S, Engel WK, Summers CG. Source: Archives of Ophthalmology. 2001 May; 119(5): 677-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346395
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High-concentration (20 mug/g) tacalcitol ointment therapy on refractory psoriasis vulgaris with low response to topical corticosteroids. Author(s): Katayama I, Ohkawara A, Ohkido M, Harada S, Tamaki K, Nakagawa H, Hori Y, Nishiyama S. Source: European Journal of Dermatology : Ejd. 2002 November-December; 12(6): 553-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459526
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High-dose corticosteroids for asthma. Author(s): Payne D. Source: Lancet. 2000 October 21; 356(9239): 1444. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11052616
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High-dose systemic corticosteroids can arrest recurrences of severe mucocutaneous erythema multiforme. Author(s): Martinez AE, Atherton DJ. Source: Pediatric Dermatology. 2000 March-April; 17(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10792793
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Higher dose inhaled corticosteroids in childhood asthma. Author(s): Keeley D. Source: Bmj (Clinical Research Ed.). 2001 March 3; 322(7285): 504-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11230052
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High-titer acquired factor V inhibitor responsive to corticosteroids and cyclophosphamide in a patient with two malignant tumors. Author(s): Bayani N, Rugina M, Haddad-Vergnes L, Lelong F. Source: American Journal of Hematology. 2002 September; 71(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221671
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Hippocampal damage mediated by corticosteroids--a neuropsychiatric research challenge. Author(s): Hoschl C, Hajek T. Source: European Archives of Psychiatry and Clinical Neuroscience. 2001; 251 Suppl 2: Ii81-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824844
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Histopathologic changes of thymoma preoperatively treated with corticosteroids. Author(s): Tateyama H, Takahashi E, Saito Y, Fukai I, Fujii Y, Niwa H, Eimoto T. Source: Virchows Archiv : an International Journal of Pathology. 2001 March; 438(3): 238-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11315620
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How do corticosteroids work in asthma? Author(s): Barnes PJ, Adcock IM. Source: Annals of Internal Medicine. 2003 September 2; 139(5 Pt 1): 359-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12965945
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Human lymphocyte subpopulations. Effect of corticosteroids. Author(s): Yu DT, Clements PJ, Paulus HE, Peter JB, Levy J, Barnett EV. Source: The Journal of Clinical Investigation. 1974 February; 53(2): 565-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344571
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Hyperammonia possibly due to corticosteroids. Author(s): Hawley RJ. Source: Archives of Neurology. 2000 July; 57(7): 1085-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10891998
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Hypersensitivity to efavirenz treated with corticosteroids in a 6-year-old child. Author(s): Foti JL, Piatt JP. Source: Aids Patient Care and Stds. 2003 January; 17(1): 1-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614514
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Hypersensitivity to topical corticosteroids in otitis externa. Author(s): Wilkinson SM, Beck MH. Source: The Journal of Laryngology and Otology. 1993 July; 107(7): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15125274
Studies
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Hypothalamic-pituitary-adrenal axis function after inhaled corticosteroids: unreliability of urinary free cortisol estimation. Author(s): Fink RS, Pierre LN, Daley-Yates PT, Richards DH, Gibson A, Honour JW. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 October; 87(10): 4541-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364432
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Idiopathic thrombocytopenic purpura: a retrospective analysis in 139 patients of the influence of age on the response to corticosteroids, splenectomy and danazol. Author(s): Andres E, Zimmer J, Noel E, Kaltenbach G, Koumarianou A, Maloisel F. Source: Drugs & Aging. 2003; 20(11): 841-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964890
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Inappropriate prescription of corticosteroids in respiratory infections. Author(s): Kumar S. Source: Indian Pediatrics. 2003 November; 40(11): 1111. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660856
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Increasing compliance with inhaled corticosteroids through the use of combination therapy. Author(s): Holt S, Masoli M, Beasley R. Source: The Journal of Allergy and Clinical Immunology. 2004 February; 113(2): 219-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767433
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Inhaled corticosteroids and hospitalisation due to exacerbation of COPD. Author(s): Bourbeau J, Ernst P, Cockcoft D, Suissa S. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 August; 22(2): 286-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952262
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Inhaled corticosteroids and urinary free cortisol. Author(s): Pescollderungg L, Peroni DG, Pietrobelli A, Radetti G. Source: Pediatrics. 2003 December; 112(6 Pt 1): 1464-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654640
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Inhaled corticosteroids in chronic obstructive pulmonary disease and risk of death and hospitalization: time-dependent analysis. Author(s): Fan VS, Bryson CL, Curtis JR, Fihn SD, Bridevaux PO, McDonell MB, Au DH. Source: American Journal of Respiratory and Critical Care Medicine. 2003 December 15; 168(12): 1488-94. Epub 2003 October 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525798
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Inhaled corticosteroids in chronic obstructive pulmonary disease. Author(s): Sutherland ER. Source: Annals of Internal Medicine. 2003 November 18; 139(10): 864; Author Reply 8645. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623628
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Inhaled corticosteroids in COPD and mortality: inaccuracies? Author(s): Suissa S. Source: American Journal of Respiratory and Critical Care Medicine. 2004 May 15; 169(10): 1165-6; Author Reply 1166. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15132963
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Inhaled corticosteroids in the long-term management of patients with chronic obstructive pulmonary disease. Author(s): Sin DD, Man SF. Source: Drugs & Aging. 2003; 20(12): 867-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565780
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Inhaled corticosteroids reduce the progression of airflow limitation in chronic obstructive pulmonary disease: a meta-analysis. Author(s): Sutherland ER, Allmers H, Ayas NT, Venn AJ, Martin RJ. Source: Thorax. 2003 November; 58(11): 937-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586043
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Inhaled corticosteroids with/without long-acting beta-agonists reduce the risk of rehospitalization and death in COPD patients. Author(s): Soriano JB, Kiri VA, Pride NB, Vestbo J. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2003; 2(1): 67-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720023
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Inhaled corticosteroids: devices and deposition. Author(s): Rubin BK. Source: Paediatric Respiratory Reviews. 2004; 5 Suppl A: S103-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980252
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Inhaled corticosteroids: past lessons and future issues. Author(s): Allen DB, Bielory L, Derendorf H, Dluhy R, Colice GL, Szefler SJ. Source: The Journal of Allergy and Clinical Immunology. 2003 September; 112(3 Suppl): S1-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515117
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Inhaled corticosteroids: why do physicians and patients fail to comply with guidelines for managing asthma? Author(s): Reed CE. Source: Mayo Clinic Proceedings. 2004 April; 79(4): 453-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15065608
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In-hospital mortality and long-term use of inhaled corticosteroids. Author(s): Punnam SR. Source: Archives of Internal Medicine. 2004 January 26; 164(2): 222; Author Reply 222-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744849
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Insulin resistance complicating pregnancy in a human immunodeficiency virusinfected patient treated with protease inhibitors and corticosteroids. Author(s): Aschkenazi S, Rochelson B, Bernasko J, Kaplan J. Source: Obstetrics and Gynecology. 2003 November; 102(5 Pt 2): 1210-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607060
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Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. Author(s): Loutfy MR, Blatt LM, Siminovitch KA, Ward S, Wolff B, Lho H, Pham DH, Deif H, LaMere EA, Chang M, Kain KC, Farcas GA, Ferguson P, Latchford M, Levy G, Dennis JW, Lai EK, Fish EN. Source: Jama : the Journal of the American Medical Association. 2003 December 24; 290(24): 3222-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693875
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Intranasal corticosteroids for asthma control in people with coexisting asthma and rhinitis. Author(s): Taramarcaz P, Gibson PG. Source: Cochrane Database Syst Rev. 2003; (4): Cd003570. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583983
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Intravenous corticosteroids to reduce gemtuzumab ozogamicin infusion reactions. Author(s): Giles FJ, Cortes JE, Halliburton TA, Mallard SJ, Estey EH, Waddelow TA, Lim JT. Source: The Annals of Pharmacotherapy. 2003 September; 37(9): 1182-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921496
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Is there a role for systemic corticosteroids in the management of stable chronic obstructive pulmonary disease? Author(s): Wood-Baker R. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2003; 2(6): 451-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14719984
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Juvenile pemphigus foliaceus treated with sublesional corticosteroids. Author(s): Qureshi WA, Ali A, Bhol KC, Ahmed AR. Source: International Journal of Dermatology. 1997 November; 36(11): 848-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9427078
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Kaposi's sarcoma in a patient with erythroblastopenia and thymoma: reactivation after topical corticosteroids. Author(s): Perez E, Barnadas MA, Garcia-Patos V, Pedro C, Curell R, Sander CA, Kind P, de Moragas JM, Alomar A. Source: Dermatology (Basel, Switzerland). 1998; 197(3): 264-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9812034
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Kaposi's sarcoma in an elderly patient with rheumatoid arthritis after intra-articular corticosteroids. Author(s): Burnet SP, McNeil JD. Source: Rheumatology (Oxford, England). 2002 January; 41(1): 107-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11792889
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KW-2149-induced pulmonary toxicity is not prevented by corticosteroids: a phase I and pharmacokinetic study. Author(s): Schrijvers D, Catimel G, Highley M, Hoppener FJ, Dirix L, De Bruijn E, Droz JP, Van Oosterom AT. Source: Anti-Cancer Drugs. 1999 August; 10(7): 633-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10507312
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Laser scar revision: comparison study of 585-nm pulsed dye laser with and without intralesional corticosteroids. Author(s): Alster T. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2003 January; 29(1): 25-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534508
Studies
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Lichen planus actinicus treated with acitretin and topical corticosteroids. Author(s): Jansen T, Gambichler T, von Kobyletzki L, Altmeyer P. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 March; 16(2): 174-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046829
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Linear growth of prepubertal asthmatic Thai children receiving long-term inhaled corticosteroids. Author(s): Visitsunthorn N, Moungnoi P, Saengsiriwut A, Wacharasindhu S. Source: J Med Assoc Thai. 2002 August; 85 Suppl 2: S599-606. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403238
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Linear scleroderma "en coup de sabre" coexisting with plaque-morphea: neuroradiological manifestation and response to corticosteroids. Author(s): Unterberger I, Trinka E, Engelhardt K, Muigg A, Eller P, Wagner M, Sepp N, Bauer G. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 661-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700315
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Local and systemic administration of corticosteroids in the treatment of olfactory loss. Author(s): Heilmann S, Huettenbrink KB, Hummel T. Source: American Journal of Rhinology. 2004 January-February; 18(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15035568
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Local side-effects of inhaled corticosteroids in asthmatic children: influence of drug, dose, age, and device. Author(s): Dubus JC, Marguet C, Deschildre A, Mely L, Le Roux P, Brouard J, Huiart L; Reseau de Recherche Clinique en Pneumonologie Pediatrique. Source: Allergy. 2001 October; 56(10): 944-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576072
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Local treatment of tendinopathies: a comparison between tropisetron and depot corticosteroids combined with local anesthetics. Author(s): Stratz T, Farber L, Muller W. Source: Scandinavian Journal of Rheumatology. 2002; 31(6): 366-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492253
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Local vs systemic corticosteroids in the treatment of carpal tunnel syndrome. Author(s): Wong SM, Hui AC, Tang A, Ho PC, Hung LK, Wong KS, Kay R, Li E. Source: Neurology. 2001 June 12; 56(11): 1565-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11402116
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Locally administered ocular corticosteroids: benefits and risks. Author(s): McGhee CN, Dean S, Danesh-Meyer H. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(1): 33-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11820911
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Long-acting beta2-agonist monotherapy vs continued therapy with inhaled corticosteroids in patients with persistent asthma: a randomized controlled trial. Author(s): Lazarus SC, Boushey HA, Fahy JV, Chinchilli VM, Lemanske RF Jr, Sorkness CA, Kraft M, Fish JE, Peters SP, Craig T, Drazen JM, Ford JG, Israel E, Martin RJ, Mauger EA, Nachman SA, Spahn JD, Szefler SJ; Asthma Clinical Research Network for the National Heart, Lung, and Blood Institute. Source: Jama : the Journal of the American Medical Association. 2001 May 23-30; 285(20): 2583-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11368732
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Long-acting beta2-agonists or leukotriene receptor antagonists as add-on therapy to inhaled corticosteroids for the treatment of persistent asthma. Author(s): Ringdal N. Source: Drugs. 2003; 63 Suppl 2: 21-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984078
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Long-acting beta-agonist treatment in patients with persistent asthma already receiving inhaled corticosteroids. Author(s): Hancox RJ, Taylor DR. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2001; 15(1): 11-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11437672
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Long-term changes in mycophenolic acid exposure in combination with tacrolimus and corticosteroids are dose dependent and not reflected by trough plasma concentration: a prospective study in 100 de novo renal allograft recipients. Author(s): Kuypers DR, Claes K, Evenepoel P, Maes B, Coosemans W, Pirenne J, Vanrenterghem Y. Source: Journal of Clinical Pharmacology. 2003 August; 43(8): 866-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953344
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Long-term cognitive benefits of antenatal corticosteroids for prematurely born children with cranial ultrasound abnormalities. Author(s): Arad I, Durkin MS, Hinton VJ, Kuhn L, Chiriboga C, Kuban K, Bellinger D. Source: American Journal of Obstetrics and Gynecology. 2002 April; 186(4): 818-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967514
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Long-term effectiveness of danazol corticosteroids and cytotoxic drugs in the treatment of hematologic manifestations of systemic lupus erythematosus. Author(s): Avina-Zubieta JA, Galindo-Rodriguez G, Robledo I, Vela-Ojeda J, VadilloBuenfil M, Rosas-Cabral A, Salazar-Exaire D. Source: Lupus. 2003; 12(1): 52-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587827
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Long-term effects of inhaled corticosteroids on FEV1 in patients with chronic obstructive pulmonary disease. A meta-analysis. Author(s): Highland KB, Strange C, Heffner JE. Source: Annals of Internal Medicine. 2003 June 17; 138(12): 969-73. Erratum In: Ann Intern Med. 2003 November 18; 139(10): 873. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809453
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Long-term management of asthma in children: effectiveness of inhaled corticosteroids compared to other medications. Author(s): National Asthma Education and Prevention Program. Source: The Journal of Allergy and Clinical Immunology. 2002 November; 110(5 Suppl): S147-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518556
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Long-term management of asthma in children: safety of inhaled corticosteroids. Author(s): National Asthma Education and Prevention Program. Source: The Journal of Allergy and Clinical Immunology. 2002 November; 110(5 Suppl): S160-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518557
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Loss of response to treatment with leukotriene receptor antagonists but not inhaled corticosteroids in patients over 50 years of age. Author(s): Creticos P, Knobil K, Edwards LD, Rickard KA, Dorinsky P. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 April; 88(4): 401-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11991558
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Low dose inhaled corticosteroids and the prevention of death from asthma. Author(s): Kips JC, Pauwels RA. Source: Thorax. 2001 September; 56 Suppl 2: Ii74-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11514710
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Malpractice claims regarding corticosteroids. Author(s): Falliers CJ. Source: Archives of Internal Medicine. 2003 May 12; 163(9): 1112-3; Author Reply 1113. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742813
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Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Author(s): Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ. Source: Chest. 2002 November; 122(5): 1543-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426251
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Maximal airway response in adolescents with long-term asthma remission and persisting airway hypersensitivity: its profile and the effect of inhaled corticosteroids. Author(s): Koh YY, Park Y, Kim CK. Source: Chest. 2002 October; 122(4): 1214-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377844
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Measuring the effectiveness of inhaled corticosteroids for COPD is not easy! Author(s): Samet JM. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 1; 168(1): 1-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826590
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Method for confirmation of synthetic corticosteroids in doping urine samples by liquid chromatography-electrospray ionisation mass spectrometry. Author(s): Fluri K, Rivier L, Dienes-Nagy A, You C, Maitre A, Schweizer C, Saugy M, Mangin P. Source: J Chromatogr A. 2001 August 10; 926(1): 87-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11554422
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Minimal reactivation of Kaposi's sarcoma-associated herpesvirus by corticosteroids in latently infected B cell lines. Author(s): Zoeteweij JP, Rinderknecht AS, Davis DA, Yarchoan R, Blauvelt A. Source: Journal of Medical Virology. 2002 March; 66(3): 378-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793390
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Mode of action of intranasal corticosteroids. Author(s): Mygind N, Nielsen LP, Hoffmann HJ, Shukla A, Blumberga G, Dahl R, Jacobi H. Source: The Journal of Allergy and Clinical Immunology. 2001 July; 108(1 Suppl): S16-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11449202
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Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Author(s): Halliday HL, Ehrenkranz RA, Doyle LW. Source: Cochrane Database Syst Rev. 2003; (1): Cd001144. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535400
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Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Author(s): Cochrane Database Syst Rev. 2003;(1):CD001146 Source: Cochrane Database Syst Rev. 2001; (1): Cd001144. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535402
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Modulation of the atopy patch test reaction by topical corticosteroids and tar. Author(s): Langeveld-Wildschut EG, Riedl H, Thepen T, Bihari IC, Bruijnzeel PL, Bruijnzeel-Koomen CA. Source: The Journal of Allergy and Clinical Immunology. 2000 October; 106(4): 737-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11031345
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Molecular mechanisms of corticosteroids in allergic diseases. Author(s): Barnes PJ. Source: Allergy. 2001 October; 56(10): 928-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576070
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Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Author(s): Phipatanakul W, Greene C, Downes SJ, Cronin B, Eller TJ, Schneider LC, Irani AM. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 July; 91(1): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877449
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Monthly corticosteroids decrease neutralizing antibodies to IFNbeta1 b: a randomized trial in multiple sclerosis. Author(s): Pozzilli C, Antonini G, Bagnato F, Mainero C, Tomassini V, Onesti E, Fantozzi R, Galgani S, Pasqualetti P, Millefiorini E, Spadaro M, Dahlke F, Gasperini C. Source: Journal of Neurology. 2002 January; 249(1): 50-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11954868
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Multiple courses of antenatal corticosteroids are associated with early severe lung disease in preterm neonates. Author(s): Banks BA, Macones G, Cnaan A, Merrill JD, Ballard PL, Ballard RA; North American TRH Study Group. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 March; 22(2): 101-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11896513
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Multiple courses of antenatal corticosteroids: a systematic review and meta-analysis. Author(s): Aghajafari F, Murphy K, Willan A, Ohlsson A, Amankwah K, Matthews S, Hannah M. Source: American Journal of Obstetrics and Gynecology. 2001 November; 185(5): 107380. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717636
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Multiple versus single courses of antenatal corticosteroids for preterm birth: a pilot study. Author(s): Aghajafari F, Murphy K, Ohlsson A, Amankwah K, Matthews S, Hannah ME. Source: J Obstet Gynaecol Can. 2002 April; 24(4): 321-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196868
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Multiple vertebral compression fractures in a patient treated with corticosteroids for cystic fibrosis. Author(s): Yen D, Hedden D. Source: Canadian Journal of Surgery. Journal Canadien De Chirurgie. 2002 October; 45(5): 383-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12387548
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Muscular mass assessed by ultrasonography after administration of low-dose corticosteroids and muscle relaxants in critically ill hemiplegic patients. Author(s): Moukas M, Vassiliou MP, Amygdalou A, Mandragos C, Takis F, Behrakis PK. Source: Clinical Nutrition (Edinburgh, Lothian). 2002 August; 21(4): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135589
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Myasthenia gravis, corticosteroids and osteoporosis prophylaxis. Author(s): Smith GD, Stevens DL, Fuller GN. Source: Journal of Neurology. 2001 February; 248(2): 151. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11284137
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Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids. Author(s): Craig TJ, Teets S, Lehman EB, Chinchilli VM, Zwillich C. Source: The Journal of Allergy and Clinical Immunology. 1998 May; 101(5): 633-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9600500
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Nasal corticosteroids, first choice in moderate to severe allergic rhinitis. What prevents general practitioners from using them? Author(s): Fokkens WJ. Source: Allergy. 2003 August; 58(8): 724-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859548
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Nasal eosinophilia and IL-5 mRNA expression in seasonal allergic rhinitis induced by natural allergen exposure: effect of topical corticosteroids. Author(s): Masuyama K, Till SJ, Jacobson MR, Kamil A, Cameron L, Juliusson S, Lowhagen O, Kay AB, Hamid QA, Durham SR. Source: The Journal of Allergy and Clinical Immunology. 1998 October; 102(4 Pt 1): 6107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9802369
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Nasal septal perforation in a patient with allergic bronchopulmonary aspergillosis and rhinitis on long term corticosteroids. Author(s): Deepak D, Panjabi C, Gudwani S, Chaudhary N, Shah A. Source: Asian Pac J Allergy Immunol. 2001 December; 19(4): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12009079
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Nebulised corticosteroids in the treatment of patients with asthma. Author(s): Hill JM. Source: Thorax. 1999 August; 54(8): 661-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10413715
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Necrobiosis lipoidica: treatment by hyperbaric oxygen and local corticosteroids. Author(s): Bouhanick B, Verret JL, Gouello JP, Berrut G, Marre M. Source: Diabetes & Metabolism. 1998 April; 24(2): 156-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9592641
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Necrotizing enterocolitis, pathogenesis and the protector effect of prenatal corticosteroids. Author(s): Precioso AR, Proenca RS. Source: Revista Do Hospital Das Clinicas. 2002 September-October; 57(5): 243-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436182
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Neonatal effects and serum cortisol levels after multiple courses of maternal corticosteroids. Author(s): Lenke R. Source: Obstetrics and Gynecology. 1998 February; 91(2): 316. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9469299
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Neutrophil and monocyte adhesion molecules in bronchopulmonary dysplasia, and effects of corticosteroids. Author(s): Ballabh P, Simm M, Kumari J, Krauss AN, Jain A, Califano C, Lesser ML, Cunningham-Rundles S. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2004 January; 89(1): F76-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711863
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Nevirapine-induced hepatitis treated with corticosteroids? Author(s): Leitze Z, Nadeem A, Choudhary A, Saul Z, Roberts I, Manthous CA. Source: Aids (London, England). 1998 June 18; 12(9): 1115-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9662216
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New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use. Author(s): Brazzini B, Pimpinelli N. Source: American Journal of Clinical Dermatology. 2002; 3(1): 47-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817968
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New corticosteroids for the treatment of ocular inflammation. Author(s): Whitcup SM, Ferris FL 3rd. Source: American Journal of Ophthalmology. 1999 May; 127(5): 597-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10334354
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New immunosuppressive agents: a way to get rid of corticosteroids? Author(s): Morelon E, Kreis H. Source: Transplantation. 2000 November 15; 70(9): 1271-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11087138
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NIH reaffirms antenatal corticosteroids for preterm women. Author(s): Cockey CD. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2000 December-2001 January; 4(6): 17-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11898167
Studies
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No permanent reduction in bone mineral density during treatment of polymyalgia rheumatica and temporal arteritis using low dose corticosteroids. Author(s): Haugeberg G, Myklebust G, Dovland H, Mikkelsen B, Gran JT. Source: Scandinavian Journal of Rheumatology. 2000; 29(3): 163-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898068
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Nocturnal asthma uncontrolled by inhaled corticosteroids: theophylline or longacting beta2 agonists? Author(s): Holimon TD, Chafin CC, Self TH. Source: Drugs. 2001; 61(3): 391-418. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11293649
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Nodular fasciitis: response to intralesional corticosteroids. Author(s): Graham BS, Barrett TL, Goltz RW. Source: Journal of the American Academy of Dermatology. 1999 March; 40(3): 490-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10071327
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Nonspecific interstitial pneumonia/fibrosis completely recovered by adding cyclophosphamide to corticosteroids. Author(s): Nanki N, Fujita J, Yamaji Y, Maeda H, Kurose T, Kaji M, Satoh K, Miyatani K, Yamadori I, Ohtsuki Y, Ishida T. Source: Intern Med. 2002 October; 41(10): 867-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413012
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NSAIDs/corticosteroids--primum non nocere. Author(s): Dequeker J. Source: Advances in Experimental Medicine and Biology. 1999; 455: 319-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10599363
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Obstructive sleep apnea in children: do intranasal corticosteroids help? Author(s): Nixon GM, Brouillette RT. Source: American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions. 2002; 1(3): 159-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720053
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Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) improves healthrelated quality of life in adults previously receiving inhaled corticosteroids. Author(s): Hampel FC Jr, Sugar M, Parasuraman B, Uryniak T, Liljas B. Source: Adv Ther. 2004 January-February; 21(1): 27-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15191155
102
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Once-daily inhaled corticosteroids for the treatment of asthma. Author(s): Boulet LP. Source: Current Opinion in Pulmonary Medicine. 2004 January; 10(1): 15-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749601
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Optimizing delivery of inhaled corticosteroids: matching drugs with devices. Author(s): O'Riordan TG. Source: Journal of Aerosol Medicine : the Official Journal of the International Society for Aerosols in Medicine. 2002 Fall; 15(3): 245-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12396412
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Oral corticosteroids in cat-scratch disease. Author(s): Lerdluedeeporn P, Krogstad P, Roberts RL, Stiehm ER. Source: Clinical Pediatrics. 2003 January-February; 42(1): 71-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635985
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Oral vs inhaled corticosteroids following emergency department discharge of patients with acute asthma. Author(s): Marik PE, Varon J. Source: Chest. 2002 June; 121(6): 1735-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065330
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Orbital myositis in a patient with primary biliary cirrhosis: successful treatment with methotrexate and corticosteroids. Author(s): Magrini L, Rotiroti G, Conti F, Viganego F, Alessandri C, Picardo V, Valesini G. Source: Isr Med Assoc J. 2003 November; 5(11): 825-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14650113
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Outcomes of African American kidney transplant recipients treated with sirolimus, tacrolimus, and corticosteroids. Author(s): Hricik DE, Anton HA, Knauss TC, Rodriguez V, Seaman D, Siegel C, Valente J, Schulak JA. Source: Transplantation. 2002 July 27; 74(2): 189-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12151730
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Outcomes of African-American kidney-transplant recipients treated with sirolimus, tacrolimus, and corticosteroids. Author(s): Egidi MF, Gaber AO. Source: Transplantation. 2003 February 27; 75(4): 572; Author Reply 573. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605133
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Overview: why are corticosteroids ineffective in COPD? Author(s): Adcock IM, Chung KF. Source: Curr Opin Investig Drugs. 2002 January; 3(1): 58-60. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12054074
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Perception of airway narrowing during reduction of inhaled corticosteroids and asthma exacerbation. Author(s): Salome CM, Leuppi JD, Freed R, Marks GB. Source: Thorax. 2003 December; 58(12): 1042-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645970
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Percutaneous absorption of drugs used in atopic eczema: pimecrolimus permeates less through skin than corticosteroids and tacrolimus. Author(s): Billich A, Aschauer H, Aszodi A, Stuetz A. Source: International Journal of Pharmaceutics. 2004 January 9; 269(1): 29-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698574
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Perinatal corticosteroids: A review of research. Part I: Antenatal administration. Author(s): Purdy IB, Wiley DJ. Source: Neonatal Netw. 2004 March-April; 23(2): 15-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15077857
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Pharmaceutical characteristics that influence the clinical efficacy of inhaled corticosteroids. Author(s): Kelly HW. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 October; 91(4): 326-34; Quiz 334-5, 404. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582810
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Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation. Author(s): Anglicheau D, Flamant M, Schlageter MH, Martinez F, Cassinat B, Beaune P, Legendre C, Thervet E. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 November; 18(11): 2409-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551375
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Postnatal corticosteroids for preterm infants--do what we say, not what we do. Author(s): Jobe AH. Source: The New England Journal of Medicine. 2004 March 25; 350(13): 1349-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044647
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Potential adverse effects of the inhaled corticosteroids. Author(s): McDermott L, O'Dowd L. Source: The Journal of Allergy and Clinical Immunology. 2004 April; 113(4): 788; Author Reply 788-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15112670
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Preoperative corticosteroids for reactive airway? Author(s): Bishop MJ. Source: Anesthesiology. 2004 May; 100(5): 1047-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114197
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Prescription drugs uses and effects. Corticosteroids. Author(s): Jordan S, Griffiths H. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2004 March 17-23; 18(27): 2P. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061025
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Pre-treatment with corticosteroids and a single cycle of high dose albendazole for subarachnoidal cysticercosis. Author(s): Marquez-Caraveo C, Gongora-Rivera F, Santos Zambrano J, Hernandez R, Soto-Hernandez JL. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 June; 75(6): 938-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15146024
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QSAR modeling with the electrotopological state indices: corticosteroids. Author(s): de Gregorio C, Kier LB, Hall LH. Source: Journal of Computer-Aided Molecular Design. 1998 November; 12(6): 557-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9879503
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Quantification of corticosteroids in human plasma by liquid chromatographythermospray mass spectrometry using stable isotope dilution. Author(s): Shibasaki H, Furuta T, Kasuya Y. Source: J Chromatogr B Biomed Sci Appl. 1997 April 25; 692(1): 7-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9187377
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Quantitative structure-pharmacokinetic/pharmacodynamic relationships of corticosteroids in man. Author(s): Mager DE, Jusko WJ. Source: Journal of Pharmaceutical Sciences. 2002 November; 91(11): 2441-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379930
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Rationale for the use of topical corticosteroids in melasma. Author(s): Menter A. Source: J Drugs Dermatol. 2004 March-April; 3(2): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15098972
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Real time assay of Aspergillus should be used in SARS patients receiving corticosteroids. Author(s): Wu YP, Wei R, Verhoef J. Source: Bmj (Clinical Research Ed.). 2003 December 13; 327(7428): 1405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670903
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Regulation of hippocampal parkin protein by corticosteroids. Author(s): Horowitz JM, Pastor DM, Kar S, Arinsburg SA, Hallas BH, Torres G. Source: Neuroreport. 2003 December 19; 14(18): 2327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663185
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Remission of idiopathic retroperitoneal fibrosis after sequential therapy with corticosteroids and tamoxifen. Author(s): Tan MO, Uygur MC, Diker Y, Erol D. Source: Urologia Internationalis. 2003; 71(4): 426-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646446
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Repeat courses of antenatal corticosteroids: the controversy continues. Author(s): Guinn DA. Source: American Journal of Obstetrics and Gynecology. 2004 March; 190(3): 585-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041984
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Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease. Author(s): Crowther CA, Harding J. Source: Cochrane Database Syst Rev. 2003; (3): Cd003935. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917996
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Repeat prenatal corticosteroids: who still recommends their use and why? Author(s): McLaughlin KJ, Crowther CA. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2003 June; 43(3): 199-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14712984
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Repeated antenatal corticosteroids: effects on cerebral palsy and childhood behavior. Author(s): French NP, Hagan R, Evans SF, Mullan A, Newnham JP. Source: American Journal of Obstetrics and Gynecology. 2004 March; 190(3): 588-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15041985
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Role of corticosteroids in septic shock. Author(s): Burry LD, Wax RS. Source: The Annals of Pharmacotherapy. 2004 March; 38(3): 464-72. Epub 2004 January 23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970369
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Role of post-operative topical corticosteroids in recurrence rate after pterygium excision with conjunctival autograft. Author(s): Yaisawang S, Piyapattanakorn P. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S215-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929992
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Safety and tolerability profiles of intranasal antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis. Author(s): Salib RJ, Howarth PH. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2003; 26(12): 863-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959630
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Safety of inhaled corticosteroids delivered by plastic and metal spacers. Author(s): Amirav I, Mansour Y, Tiosano T, Chamny S, Chirurg S, Oren S, Grossman Z, Kahana L, Kahan E, Newhouse MT; Ipros Network. Source: Archives of Disease in Childhood. 2003 June; 88(6): 527-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765924
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Safety of the newer inhaled corticosteroids in childhood asthma. Author(s): Randell TL, Donaghue KC, Ambler GR, Cowell CT, Fitzgerald DA, van Asperen PP. Source: Paediatric Drugs. 2003; 5(7): 481-504. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837120
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Sensitivity and validity of three bronchial provocation tests to demonstrate the effect of inhaled corticosteroids in asthma. Author(s): Koskela HO, Hyvarinen L, Brannan JD, Chan HK, Anderson SD. Source: Chest. 2003 October; 124(4): 1341-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14555564
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Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa. Author(s): Guillevin L, Mahr A, Cohen P, Larroche C, Queyrel V, Loustaud-Ratti V, Imbert B, Hausfater P, Roudier J, Bielefeld P, Petitjean P, Smadja D; French Vasculitis Study Group. Source: Arthritis and Rheumatism. 2004 June 15; 51(3): 482-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188337
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Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes. Author(s): Lee MJ, Davies J, Guinn D, Sullivan L, Atkinson MW, McGregor S, Parilla BV, Hanlon-Lundberg K, Simpson L, Stone J, Wing D, Ogasawara K, Muraskas J. Source: Obstetrics and Gynecology. 2004 February; 103(2): 274-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14754695
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Spontaneous intracranial hypotension: quick clinical and magnetic resonance imaging response to corticosteroids. A case report. Author(s): Pascual LF, Santos S, Escalza I, Iniguez C, Morales-Asin F. Source: Headache. 2002 May; 42(5): 359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047337
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Stopping inhaling corticosteroids in COPD. Author(s): Pesola GR, Dogra S. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 256-7; Author Reply 257. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851248
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Supratarsal injection of corticosteroids in the treatment of refractory vernal keratoconjunctivitis. Author(s): Singh S, Pal V, Dhull CS. Source: Indian J Ophthalmol. 2001 December; 49(4): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930116
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Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Author(s): Irwin RS, Madison JM. Source: The New England Journal of Medicine. 2003 June 26; 348(26): 2679-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826643
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The adverse effects of corticosteroids in central serous chorioretinopathy. Author(s): De Nijs E, Brabant P, De Laey JJ. Source: Bull Soc Belge Ophtalmol. 2003; (289): 35-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14619628
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The comparison of efficacies of topical corticosteroids and nonsteroidal antiinflammatory drops on dry eye patients: a clinical and immunocytochemical study. Author(s): Avunduk AM, Avunduk MC, Varnell ED, Kaufman HE. Source: American Journal of Ophthalmology. 2003 October; 136(4): 593-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516798
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The comparison of efficacies of topical corticosteroids and nonsteroidal antiinflammatory drops on dry eye patients: a clinical and immunocytochemical study. Author(s): Chan CK, Lam DS. Source: American Journal of Ophthalmology. 2004 June; 137(6): 1157-8; Author Reply 1158. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15183818
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The use of corticosteroids in syntomathic asthma in childhood. Author(s): Ranganathan SC, McKenzie SA. Source: Minerva Pediatr. 2003 August; 55(4): 357-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608278
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The use of corticosteroids versus other treatments for Graves' ophthalmopathy: a quantitative evaluation. Author(s): Abalkhail S, Doi SA, Al-Shoumer KA. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 November; 9(11): Cr477-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586273
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The use of inhaled corticosteroids for persistent asthma in infants and young children. Author(s): Berger WE, Shapiro GG. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2004 April; 92(4): 387-399; Quiz 399-402, 463. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104189
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Topical corticosteroids after keratorefractive surgery. Author(s): Annonier P. Source: Journal of Cataract and Refractive Surgery. 2003 October; 29(10): 1853-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604700
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Topical corticosteroids in atopic dermatitis. Author(s): Atherton DJ. Source: Bmj (Clinical Research Ed.). 2003 October 25; 327(7421): 942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576221
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Treatment of Sydenham chorea with corticosteroids. Author(s): Cardoso F, Maia D, Cunningham MC, Valenca G. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 November; 18(11): 1374-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639684
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Trends in use of inhaled corticosteroids for asthma management: 1994-1998. Author(s): Allen-Ramey FC, Samet JM, Rand CS, Joseph CL. Source: Annals of Epidemiology. 2004 March; 14(3): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036218
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Update of growth effects of inhaled and intranasal corticosteroids. Author(s): Skoner D. Source: Current Opinion in Allergy and Clinical Immunology. 2002 February; 2(1): 7-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11964744
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Update on progress in the international, multicenter, randomized, controlled trial of corticosteroids after significant head injury (Medical Research Council CRASH Trial). Author(s): MRC CRASH Trial National Coordinators. Source: Current Opinion in Critical Care. 2003 April; 9(2): 92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657970
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Use and abuse of topical corticosteroids in infections of the skin and related structures. Author(s): Wong VK, Della Croce C, Schonfeld S, Mastrangelo AM, Lebwohl M. Source: J Drugs Dermatol. 2003 June; 2(3): 268-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12848111
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Use and misuse of corticosteroids. Author(s): Borchers AT, Keen CL, Gershwin ME. Source: Compr Ther. 2003 Summer-Fall; 29(2-3): 157-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606345
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Use of corticosteroids in anesthesia and critical care. Author(s): Wu RS. Source: Acta Anaesthesiol Sin. 2002 June; 40(2): 53-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12194390
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Use of corticosteroids in bacterial meningitis. Author(s): Feigin RD. Source: The Pediatric Infectious Disease Journal. 2004 April; 23(4): 355-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15071293
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Use of inhaled corticosteroids and risk of fractures. Author(s): van Staa TP, Leufkens HG, Cooper C. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 March; 16(3): 581-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277277
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Use of inhaled corticosteroids in children. Author(s): Devoy M. Source: Archives of Disease in Childhood. 2003 May; 88(5): 461. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716732
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Use of sequential quadrupling dose regimens to study efficacy of inhaled corticosteroids in asthma. Author(s): Phillips K, Oborne J, Harrison TW, Tattersfield AE. Source: Thorax. 2004 January; 59(1): 21-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694241
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Use of systemic corticosteroids and risk of esophageal cancer. Author(s): Sorensen HT, Mellemkjaer L, Friis S, Olsen JH. Source: Epidemiology (Cambridge, Mass.). 2002 March; 13(2): 240-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11880772
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Validation of a screening method for corticosteroids in doping analysis by liquid chromatography/tandem mass spectrometry. Author(s): Deventer K, Delbeke FT. Source: Rapid Communications in Mass Spectrometry : Rcm. 2003; 17(18): 2107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955741
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Variation in use of corticosteroids among infants < or = 1,500 grams across hospitals in three states. Author(s): Murphy KE, Reuss ML, Leviton A, Paneth N, Susser M. Source: The Journal of Maternal-Fetal Medicine. 1998 May-June; 7(3): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9642611
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Vasoconstrictive effect of topical applied corticosteroids measured by laser doppler imaging and reflectance spectroscopy. Author(s): Sommer A, Lucassen GW, Houben AJ, Neumann MH. Source: Microvascular Research. 2003 May; 65(3): 152-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12711256
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Vision loss in giant cell arteritis patients treated with alternate-day corticosteroids: comment on the article by Hoffman et al. Author(s): Spiera RF, Kupersmith M, Paget S, Spiera H. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1159-60; Author Reply 1160-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687562
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Vitiligo treated with topical corticosteroids: children with head and neck involvement respond well. Author(s): Cockayne SE, Messenger AG, Gawkrodger DJ. Source: Journal of the American Academy of Dermatology. 2002 June; 46(6): 964-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12063504
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Vogt-Koyanagi-Harada syndrome in a pregnant patient treated with high-dose systemic corticosteroids. Author(s): Doi M, Matsubara H, Uji Y. Source: Acta Ophthalmologica Scandinavica. 2000 February; 78(1): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10726799
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What are the alternatives to increasing inhaled corticosteroids for the long term control of asthma? Author(s): Flood-Page P, Barnes NC. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2001; 15(3): 185-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11437684
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What is the appropriate initial dose of corticosteroids to treat giant cell arteritis? Author(s): Wilke WS. Source: Cleve Clin J Med. 2000 August; 67(8): 546-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10946446
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What role do systemic corticosteroids, immunotherapy, and antifungal drugs play in the therapy of allergic fungal rhinosinusitis? Author(s): Ferguson BJ. Source: Archives of Otolaryngology--Head & Neck Surgery. 1998 October; 124(10): 11748. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9776199
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What to do at step 3 of the asthma guidelines-increase the dose of inhaled corticosteroids or add a long-acting beta-agonist drug? Author(s): Masoli M, Holt S, Beasley R. Source: The Journal of Allergy and Clinical Immunology. 2003 July; 112(1): 10-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847472
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Whether or not to give inhaled corticosteroids. Author(s): Wilson NM. Source: Paediatric Respiratory Reviews. 2003 September; 4(3): 267, 269-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959115
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Which is more effective for as-needed treatment of seasonal allergy symptoms: intranasal corticosteroids or oral antihistamines? Author(s): Frantz J. Source: The Journal of Family Practice. 2002 March; 51(3): 281. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978243
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Who remains undelivered more than seven days after a single course of prenatal corticosteroids and gives birth at less than 34 weeks? Author(s): McLaughlin KJ, Crowther CA, Vigneswaran P, Hancock E, Willson K. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 October; 42(4): 353-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403279
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Why do patients with atopic dermatitis refuse to apply topical corticosteroids? Author(s): Fukaya M. Source: Dermatology (Basel, Switzerland). 2000; 201(3): 242-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096196
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Withdrawal of chronic systemic corticosteroids in patients with COPD: a randomized trial. Author(s): Rice KL, Rubins JB, Lebahn F, Parenti CM, Duane PG, Kuskowski M, Joseph AM, Niewoehner DE. Source: American Journal of Respiratory and Critical Care Medicine. 2000 July; 162(1): 174-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10903238
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Working memory is more sensitive than declarative memory to the acute effects of corticosteroids: a dose-response study in humans. Author(s): Lupien SJ, Gillin CJ, Hauger RL. Source: Behavioral Neuroscience. 1999 June; 113(3): 420-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10443770
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Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Author(s): Christian Virchow J, Prasse A, Naya I, Summerton L, Harris A. Source: American Journal of Respiratory and Critical Care Medicine. 2000 August; 162(2 Pt 1): 578-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10934090
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CHAPTER 2. NUTRITION AND CORTICOSTEROIDS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and corticosteroids.
Finding Nutrition Studies on Corticosteroids 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 “corticosteroids” (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 “corticosteroids” (or a synonym): •
A preliminary study of circadian serum cortisol concentrations in response to a 72hour fast in rheumatoid arthritis patients not previously treated with corticosteroids. Author(s): Centre for Rheumatic Diseases, National Hospital, Oslo, Norway.
[email protected] Source: Fraser, D A Thoen, J Selvaag, A M Djoseland, O Forre, O Kjeldsen Kragh, J ClinRheumatol. 2001; 20(2): 85-7 0770-3198
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Acute tumor lysis syndrome induced by high-dose corticosteroids in a patient with chronic lymphatic leukemia. Author(s): Department of Internal Medicine, A, Western Galilee Hospital, Naharyia, Israel. Source: Vaisban, E Zaina, A Braester, A Manaster, J Horn, Y Ann-Hematol. 2001 May; 80(5): 314-5 0939-5555
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An evidence-based review on the use of corticosteroids in peri-operative and critical care. Author(s): Department of Anesthesiology, National Taiwan University, College of Medicine and Hospital, Taipei, Taiwan, R.O.C. Source: Han, Y Y Sun, W Z Acta-Anaesthesiol-Sin. 2002 June; 40(2): 71-9 0529-5769
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Antenatal corticosteroids for preterm birth. Author(s): Department of Obstetrics and Gynecology, University of Toronto, Mount Sinai Hospital, Ontario, Canada. Source: Murphy, K Aghajafari, F Hannah, M Semin-Perinatol. 2001 October; 25(5): 341-7 0146-0005
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Changing perspectives on the role of corticosteroids after liver transplantation. Author(s): Liver Transplant Program, University of Pennsylvania Health System, Philadelphia, PA, USA. Source: Lucey, M R Liver-Transpl-Surg. 1999 July; 5(4 Suppl 1): S58-63 1074-3022
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Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle. Author(s): First Department of Internal Medicine, School of Medicine, The University of Tokushima, Kuramoto-3-18-15, Tokushima 770-8503, Japan.
[email protected] Source: Mitsui, T Azuma, H Nagasawa, M Iuchi, T Akaike, M Odomi, M Matsumoto, T J-Neurol. 2002 August; 249(8): 1004-9 0340-5354
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Comparative efficacy and safety of inhaled corticosteroids in asthma. Author(s): Department of Pharmacy, Sunnybrook Health Science Centre, Toronto, Ontario.
[email protected] Source: Jackson, L D Polygenis, D McIvor, R A Worthington, I Can-J-Clin-Pharmacol. 1999 Spring; 6(1): 26-37 1198-581X
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Considering nasal corticosteroids to treat allergic rhinitis. Author(s): University of Washington, Seattle, USA. Source: Ellsworth, A JAAPA. 2000 December; 13(12): 77-9
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Cushing's syndrome secondary to inhaled corticosteroids mimicking HIV-associated lipodystrophy. Author(s): Heart and Chest Clinic, Southend Associate University Hospital, Westcliffon-sea, Essex, UK.
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Source: le Roux, C W Beckles, M A Besser, G M Pinching, A J Davison, A G HIV-Med. 2001 April; 2(2): 133-5 1464-2662 •
Cyclodextrins in eye drop formulations: enhanced topical delivery of corticosteroids to the eye. Author(s): Faculties of Pharmacy and Medicine, University of Iceland, Reykjavik, Iceland. Source: Loftsson, Thorsteinn Stefansson, Einar Acta-Ophthalmol-Scand. 2002 April; 80(2): 144-50 1395-3907
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Decreased consumption of corticosteroids after selenium supplementation in corticoid-dependent asthmatics. Author(s): Institute of Preventive and Clinical Medicine, Department of Clinical Immunology, Limbova 14, SK-833 01 Bratislava 37, Slovakia.
[email protected] Source: Gazdik, F Kadrabova, J Gazdikova, K Bratisl-Lek-Listy. 2002; 103(1): 22-5 00069248
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Do corticosteroids add any benefit to standard GVHD prophylaxis in allogeneic BMT? Author(s): Department of Clinical Hematology, Hospital Duran i Reynals, Institut Catala d'Oncologia, Spain.
[email protected] Source: Ancin, I Ferra, C Gallardo, D Peris, J Berlanga, J Gonzalez, J R Virgili, N Granena, A Bone-Marrow-Transplant. 2001 July; 28(1): 39-45 0268-3369
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Effect of exogenous corticosteroids on the developing central nervous system: a review. Author(s): Department of Zoology, University of Western Australia, Nedlands, Australia.
[email protected] Source: Huang, W L Dunlop, S A Harper, C G Obstet-Gynecol-Survolume 1999 May; 54(5): 336-42 0029-7828
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Effect of the long-term use of inhaled corticosteroids on bone mineral density in asthmatic women. Author(s): Departments of Physical Medicine and Rehabilitation and; Chest Disease, University of Hacettepe, Ankara, Turkey.
[email protected] Source: Sivri, A Coplu, L Respirology. 2001 June; 6(2): 131-4 1323-7799
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Effects of high doses of corticosteroids on bone metabolism. Author(s): Department of Internal Medicine, University of Turin, Italy. Source: Ardissone, P Rota, E Durelli, L Limone, P Isaia, G C J-Endocrinol-Invest. 2002 February; 25(2): 129-33 0391-4097
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Effects of inhaled corticosteroids on growth in asthmatic children. Author(s): Cystic Fibrosis/Respiratory Unit, Department of Child Health, University Hospital of Wales, Cardiff CF14 4XW, UK. Source: Creese, K H Doull, I J Curr-Allergy-Asthma-Repage 2001 March; 1(2): 122-6 1529-7322
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Efficacy of corticosteroids in acute experimental irritant contact dermatitis? Author(s): Department of Dermatology, University of California at San Francisco Medical Center, CA 94143-0989, USA. Source: Levin, C Zhai, H Bashir, S Chew, A L Anigbogu, A Stern, R Maibach, H SkinRes-Technol. 2001 November; 7(4): 214-8 0909-752X
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Health beliefs and compliance with inhaled corticosteroids by asthmatic patients in primary care practices. Author(s): Department of Family Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
[email protected] Source: Chambers, C V Markson, L Diamond, J J Lasch, L Berger, M Respir-Med. 1999 February; 93(2): 88-94 0954-6111
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Information for patients. Inhaled corticosteroids in asthma. Author(s): Firestone Institute for Respiratory Health, St Joseph's Healthcare, Hamilton, Ontario. Source: Leigh, R Can-Respir-J. 2001 Sep-October; 8(5): 331-2 1198-2241
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Inhaled corticosteroids and growth. Author(s): Children's Clinic Randers, Denmark.
[email protected] Source: Wolthers, O D J-Pediatr-Endocrinol-Metab. 2001; 14 Suppl 6: 1487-90
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Melanocortins are comparable to corticosteroids as inhibitors of traumatic ocular inflammation in rabbits. Author(s):
[email protected] Source: Naveh, N Marshall, J Graefes-Arch-Clin-Exp-Ophthalmol. 2001 November; 239(11): 840-4 0721-832X
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Perforated gastric ulcer complicating corticosteroid therapy in acute rheumatic fever. Author(s): Department of Paediatrics, Bikur Cholim General Hospital, Jerusalem, Israel. Source: Klar, A Moise, J Brand, A Seror, D Hurvitz, H Acta-Gastroenterol-Belg. 2000 Apr-June; 63(2): 236-8 0001-5644
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Perinatal corticosteroids and the developing lung. Author(s): North Trent Neonatal Intensive Care Unit, Jessop Wing, Sheffield Teaching Hospitals NHS Trust, Tree Root Walk, Sheffield S10 2SF, UK.
[email protected] Source: Gibson, Alan T Paediatr-Respir-Revolume 2002 March; 3(1): 70-6 1526-0542
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Possible role of corticosteroids in nervous system plasticity: improvement in amblyopia after optic neuritis in the fellow eye treated with steroids. Author(s): Division of Clinical Neurology, University Hospital, Queen's Medical Centre, Nottingham, UK.
[email protected] Source: Constantinescu C, S Gottlob, I Neurorehabil-Neural-Repair. 2001; 15(3): 223-7
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Review of the effect of the dosing interval for inhaled corticosteroids in asthma control. Author(s): Royal Hobart Hospital, University of Tasmania, Hobart, Australia. Source: Singer, R Wood Baker, R Intern-Med-J. 2002 March; 32(3): 72-8 1444-0903
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Role of increased environmental Aspergillus exposure for patients with chronic obstructive pulmonary disease (COPD) treated with corticosteroids in an intensive care unit. Author(s): Institute of Hygiene and Public Health, University of Bonn, Sigmund-FreudStr. 25, D-53105 Bonn, Germany. Source: Kistemann, Thomas Huneburg, HilMarch Exner, Martin Vacata, Vladimir Engelhart, Steffen Int-J-Hyg-Environ-Health. 2002 February; 204(5-6): 347-51 1438-4639
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The effects of corticosteroids on the musculoskeletal system. Author(s): Chesapeake Orthopaedic and Sports Medicine Center, Glen Burnie, Maryland, USA. Source: Crowther, C L Orthop-Nurs. 2001 Nov-December; 20(6): 33-7; quiz 37-9 07446020
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The International Sepsis Forum's controversies in sepsis: corticosteroids should be used to treat septic shock. Author(s): Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, The Hebrew University of Jerusalem, Israel. Source: Goodman, S Sprung, C L Crit-Care. 2002 October; 6(5): 381-3 1364-8535
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The use of inhaled corticosteroids in adult asthma. Author(s): Pharmacy Practice Division, University of Wisconsin School of Pharmacy, 777 Highland Avenue, Madison, WI 53705-2222, USA. Source: Staresinic, A G Sorkness, C A Med-Clin-North-Am. 2002 September; 86(5): 103547 0025-7125
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Topical allopurinol or corticosteroids and acetylcysteine in the early treatment of experimental corneal alkali burns: a pilot study. Author(s): Department of Ophthalmology, Philipps University Marburg, Germany.
[email protected] Source: Sekundo, W Augustin, A J Strempel, I Eur-J-Ophthalmol. 2002 Sep-October; 12(5): 366-72 1120-6721
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Use of oral corticosteroids and risk of fractures. Author(s): Procter & Gamble Pharmaceuticals, Staines, UK. Source: Van Staa, T P Leufkens, H G Abenhaim, L Zhang, B Cooper, C J-Bone-MinerRes. 2000 June; 15(6): 993-1000 0884-0431
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
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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 corticosteroids; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin K Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Biotin Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Healthnotes, Inc.; www.healthnotes.com
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Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Chromium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Prima Communications, Inc.www.personalhealthzone.com Potassium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10086,00.html Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com •
Food and Diet Low-Purine Diet Source: Healthnotes, Inc.; www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Tendinitis Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE CORTICOSTEROIDS
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to corticosteroids. 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 corticosteroids 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 “corticosteroids” (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 corticosteroids: •
A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress. Author(s): Brody S, Preut R, Schommer K, Schurmeyer TH. Source: Psychopharmacology. 2002 January; 159(3): 319-24. Epub 2001 November 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862365
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Adrenal corticosteroids in Chinese herbal remedies. Author(s): McConkey B. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 January; 96(1): 81-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509653
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Anticonvulsant efficiency, behavioral performance and cortisol levels: a comparison of carbamazepine (CBZ) and a fatty acid compound (SR-3). Author(s): Rabinovitz S, Mostofsky DI, Yehuda S. Source: Psychoneuroendocrinology. 2004 February; 29(2): 113-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604595
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beta-Naphthoflavone disrupts cortisol production and liver glucocorticoid responsiveness in rainbow trout. Author(s): Aluru N, Vijayan MM. Source: Aquatic Toxicology (Amsterdam, Netherlands). 2004 April 28; 67(3): 273-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15063076
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Bronchodilators and corticosteroids in the treatment of asthma. Author(s): Vianna EO, Martin RJ. Source: Drugs Today (Barc). 1998 March; 34(3): 203-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15094850
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Butterbur, a herbal remedy, confers complementary anti-inflammatory activity in asthmatic patients receiving inhaled corticosteroids. Author(s): Lee DK, Haggart K, Robb FM, Lipworth BJ. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 January; 34(1): 110-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720270
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Combination anti-inflammatory therapy: synergism in rats of NSAIDs/corticosteroids with some herbal/animal products. Author(s): Whitehouse MW, Butters DE. Source: Inflammopharmacology. 2003; 11(4): 453-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15035799
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Corticosteroid-induced apoptosis of airway epithelium: a potential mechanism for chronic airway epithelial damage in asthma. Author(s): White SR, Dorscheid DR. Source: Chest. 2002 December; 122(6 Suppl): 278S-284S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475799
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Corticosteroid-insensitive asthma: molecular mechanisms. Author(s): Adcock IM, Lane SJ. Source: The Journal of Endocrinology. 2003 September; 178(3): 347-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967328
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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C.
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Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12026233 •
Corticosteroids, eosinophils and bronchial epithelial cells: new insights into the resolution of inflammation in asthma. Author(s): Walsh GM, Sexton DW, Blaylock MG. Source: The Journal of Endocrinology. 2003 July; 178(1): 37-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12844334
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Cortisol, prolactin, growth hormone and neurovegetative responses to emotions elicited during an hypnoidal state. Author(s): Sobrinho LG, Simoes M, Barbosa L, Raposo JF, Pratas S, Fernandes PL, Santos MA. Source: Psychoneuroendocrinology. 2003 January; 28(1): 1-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445833
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Cyclosporin as an oral corticosteroid sparing agent in stable asthma. Author(s): Evans DJ, Cullinan P, Geddes DM. Source: Cochrane Database Syst Rev. 2001; (2): Cd002993. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406057
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Decreased consumption of corticosteroids after selenium supplementation in corticoid-dependent asthmatics. Author(s): Gazdik F, Kadrabova J, Gazdikova K. Source: Bratisl Lek Listy. 2002; 103(1): 22-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061082
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Dietary supplementation with creatine monohydrate prevents corticosteroid-induced attenuation of growth in young rats. Author(s): Roy BD, Bourgeois JM, Mahoney DJ, Tarnopolsky MA. Source: Canadian Journal of Physiology and Pharmacology. 2002 October; 80(10): 100814. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12450068
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Differential effects of Saint John's Wort (hypericum perforatum) on the urinary excretion of D-glucaric acid and 6beta-hydroxycortisol in healthy volunteers. Author(s): Bauer S, Stormer E, Kerb R, Johne A, Brockmoller J, Roots I. Source: European Journal of Clinical Pharmacology. 2002 December; 58(9): 581-5. Epub 2002 November 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483450
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Early detection and successful treatment of drug-induced pneumonitis with corticosteroids. Author(s): Ash-Bernal R, Browner I, Erlich R. Source: Cancer Investigation. 2002; 20(7-8): 876-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12449717
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Effect of corticosteroids and eicosapentaenoic acid/docosahexaenoic acid on prooxidant and anti-oxidant status and metabolism of essential fatty acids in patients with glomerular disorders. Author(s): Das UN, Mohan IK, Raju TR. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2001 October; 65(4): 197-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728172
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Effects of dietary fat and endurance exercise on plasma cortisol, prostaglandin E2, interferon-gamma and lipid peroxides in runners. Author(s): Venkatraman JT, Feng X, Pendergast D. Source: Journal of the American College of Nutrition. 2001 October; 20(5): 529-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11601568
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Effects of flavonoid phytochemicals on cortisol production and on activities of steroidogenic enzymes in human adrenocortical H295R cells. Author(s): Ohno S, Shinoda S, Toyoshima S, Nakazawa H, Makino T, Nakajin S. Source: The Journal of Steroid Biochemistry and Molecular Biology. 2002 March; 80(3): 355-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948020
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Effects of ginseng ingestion on growth hormone, testosterone, cortisol, and insulinlike growth factor 1 responses to acute resistance exercise. Author(s): Youl Kang H, Hwan Kim S, Jun Lee W, Byrne HK. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2002 May; 16(2): 179-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11991768
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Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Author(s): Gholap S, Kar A. Source: Pharmazie. 2003 June; 58(6): 413-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12857006
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Effects of low-frequency cranial electrostimulation on the rest-activity rhythm and salivary cortisol in Alzheimer's disease. Author(s): Scherder E, Knol D, van Someren E, Deijen JB, Binnekade R, Tilders F, Sergeant J.
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Source: Neurorehabilitation and Neural Repair. 2003 June; 17(2): 101-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814055 •
Effects of relaxing music on salivary cortisol level after psychological stress. Author(s): Khalfa S, Bella SD, Roy M, Peretz I, Lupien SJ. Source: Annals of the New York Academy of Sciences. 2003 November; 999: 374-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681158
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Gastric perforation induced by combination chemotherapy in a patient with longterm use of corticosteroids. Author(s): Yamazawa K, Matsui H, Sekiya S. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2002 August; 78(2): 165-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12175721
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Gold as an oral corticosteroid sparing agent in stable asthma. Author(s): Evans DJ, Cullinan P, Geddes DM. Source: Cochrane Database Syst Rev. 2001; (2): Cd002985. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406053
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Herbal creams used for atopic eczema in Birmingham, UK illegally contain potent corticosteroids. Author(s): Ramsay HM, Goddard W, Gill S, Moss C. Source: Archives of Disease in Childhood. 2003 December; 88(12): 1056-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670768
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Impact of the GH-cortisol ratio on the age-dependent changes in body composition. Author(s): Nass R, Thorner MO. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2002 June; 12(3): 147-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12162996
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Maternal consumption of a high-meat, low-carbohydrate diet in late pregnancy: relation to adult cortisol concentrations in the offspring. Author(s): Herrick K, Phillips DI, Haselden S, Shiell AW, Campbell-Brown M, Godfrey KM. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3554-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915635
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Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin
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in breast and prostate cancer outpatients. Author(s): Carlson LE, Speca M, Patel KD, Goodey E. Source: Psychoneuroendocrinology. 2004 May; 29(4): 448-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749092 •
Misuse of corticosteroids in some of the drugs dispensed as preparations from alternative systems of medicine in India. Author(s): Gupta SK, Kaleekal T, Joshi S. Source: Pharmacoepidemiology and Drug Safety. 2000 December; 9(7): 599-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11338919
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Participation of corticosteroids and effects of indomethacin on the acute inflammatory response of rats fed n-6 or n-3 polyunsaturated fatty acid-rich diets. Author(s): Wohlers M, Nascimento CM, Xavier RA, Ribeiro EB, Silveira VL. Source: Inflammation. 2003 February; 27(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772772
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Reduction of rise in blood pressure and cortisol release during stress by Ginkgo biloba extract (EGb 761) in healthy volunteers. Author(s): Jezova D, Duncko R, Lassanova M, Kriska M, Moncek F. Source: Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society. 2002 September; 53(3): 337-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12369732
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Remission induction therapy for childhood acute lymphoblastic leukaemia: clinical and cellular pharmacology of vincristine, corticosteroids, L-asparaginase and anthracyclines. Author(s): Ronghe M, Burke GA, Lowis SP, Estlin EJ. Source: Cancer Treatment Reviews. 2001 December; 27(6): 327-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11908926
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Salivary cortisol levels and the cortisol response to dexamethasone before and after EMDR: a case report. Author(s): Heber R, Kellner M, Yehuda R. Source: Journal of Clinical Psychology. 2002 December; 58(12): 1521-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455019
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Some gastrointestinal function regulatory Kampo medicines have modulatory effects on human plasma adrenocorticotropic hormone and cortisol levels with continual stress exposure. Author(s): Naito T, Itoh H, Takeyama M.
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Source: Biological & Pharmaceutical Bulletin. 2003 January; 26(1): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12520183 •
Sub-chronic treatment with an extract of Hypericum perforatum (St John's wort) significantly reduces cortisol and corticosterone in the rat brain. Author(s): Franklin M, Reed A, Murck H. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2004 January; 14(1): 7-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659982
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The effect of chiropractic manipulation on salivary cortisol levels. Author(s): Whelan TL, Dishman JD, Burke J, Levine S, Sciotti V. Source: Journal of Manipulative and Physiological Therapeutics. 2002 March-April; 25(3): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986575
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The effect of therapeutic touch on agitated behavior and cortisol in persons with Alzheimer's disease. Author(s): Woods DL, Dimond M. Source: Biological Research for Nursing. 2002 October; 4(2): 104-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408216
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The effects of stressful life events, coping, and cortisol on HIV infection. Author(s): Leserman J. Source: Cns Spectr. 2003 January; 8(1): 25-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627047
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The impact of abbreviated progressive muscle relaxation on salivary cortisol. Author(s): Pawlow LA, Jones GE. Source: Biological Psychology. 2002; 60(1): 1-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100842
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The impact of repetitive transcranial magnetic stimulation on pituitary hormone levels and cortisol in healthy subjects. Author(s): Evers S, Hengst K, Pecuch PW. Source: Journal of Affective Disorders. 2001 September; 66(1): 83-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11532537
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The Ironson-woods Spirituality/Religiousness Index is associated with long survival, health behaviors, less distress, and low cortisol in people with HIV/AIDS. Author(s): Ironson G, Solomon GF, Balbin EG, O'Cleirigh C, George A, Kumar M, Larson D, Woods TE.
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Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 2002 Winter; 24(1): 34-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008793 •
Treatment of atopic dermatitis and impact on quality of life: a review with emphasis on topical non-corticosteroids. Author(s): Schiffner R, Schiffner-Rohe J, Landthaler M, Stolz W. Source: Pharmacoeconomics. 2003; 21(3): 159-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558467
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Troleandomycin as an oral corticosteroid steroid sparing agent in stable asthma. Author(s): Evans DJ, Cullinan P, Geddes DM. Source: Cochrane Database Syst Rev. 2001; (2): Cd002987. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406054
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Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running. Author(s): Peters EM, Anderson R, Nieman DC, Fickl H, Jogessar V. Source: International Journal of Sports Medicine. 2001 October; 22(7): 537-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590482
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/
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The following is a specific Web list relating to corticosteroids; 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 Allergic Rhinitis Source: Integrative Medicine Communications; www.drkoop.com Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Amenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Angioedema Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Bell's Palsy Source: Healthnotes, Inc.; www.healthnotes.com Bipolar Disorder Source: Healthnotes, Inc.; www.healthnotes.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Bronchitis Source: Integrative Medicine Communications; www.drkoop.com Burns Source: Integrative Medicine Communications; www.drkoop.com Bursitis Source: Healthnotes, Inc.; www.healthnotes.com Bursitis Source: Integrative Medicine Communications; www.drkoop.com Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com
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Canker Sores Source: Healthnotes, Inc.; www.healthnotes.com Carpal Tunnel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Carpal Tunnel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com Cluster Headache Source: Healthnotes, Inc.; www.healthnotes.com Conjunctivitis Source: Integrative Medicine Communications; www.drkoop.com Conjunctivitis and Blepharitis Source: Healthnotes, Inc.; www.healthnotes.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Cutaneous Drug Reactions Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com Dupuytren's Contracture Source: Healthnotes, Inc.; www.healthnotes.com Eczema Source: Healthnotes, Inc.; www.healthnotes.com
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Eczema Source: Integrative Medicine Communications; www.drkoop.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Endocarditis Source: Integrative Medicine Communications; www.drkoop.com Epstein-Barr Virus Source: Integrative Medicine Communications; www.drkoop.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Gout Source: Healthnotes, Inc.; www.healthnotes.com Gout Source: Integrative Medicine Communications; www.drkoop.com Hay Fever Source: Healthnotes, Inc.; www.healthnotes.com Hay Fever Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hives Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com
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Lupus Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Mononucleosis Source: Integrative Medicine Communications; www.drkoop.com Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Prima Communications, Inc.www.personalhealthzone.com Pain Source: Healthnotes, Inc.; www.healthnotes.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Pericarditis Source: Integrative Medicine Communications; www.drkoop.com Pertussis Source: Integrative Medicine Communications; www.drkoop.com Photosensitivity Source: Healthnotes, Inc.; www.healthnotes.com Pink Eye Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Healthnotes, Inc.; www.healthnotes.com Psoriasis Source: Integrative Medicine Communications; www.drkoop.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com
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Reiter's Syndrome Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Healthnotes, Inc.; www.healthnotes.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Seborrheic Dermatitis Source: Healthnotes, Inc.; www.healthnotes.com Serum Sickness Source: Integrative Medicine Communications; www.drkoop.com Shingles and Postherpetic Neuralgia Source: Healthnotes, Inc.; www.healthnotes.com Shock Source: Integrative Medicine Communications; www.drkoop.com Sinus Congestion Source: Healthnotes, Inc.; www.healthnotes.com Sinusitis Source: Healthnotes, Inc.; www.healthnotes.com Syncope Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Tendinitis Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Healthnotes, Inc.; www.healthnotes.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com
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Uveitis Source: Integrative Medicine Communications; www.drkoop.com Vaginal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 Deficiency Source: Healthnotes, Inc.; www.healthnotes.com Whooping Cough Source: Integrative Medicine Communications; www.drkoop.com Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com Wounds Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Healthnotes, Inc.; www.healthnotes.com •
Alternative Therapy Apitherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,669,00.html Chiropractic Source: Integrative Medicine Communications; www.drkoop.com Guided Imagery Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,699,00.html Massage Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,716,00.html Music Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,719,00.html Testing for Stomach Acidity Source: Healthnotes, Inc.; www.healthnotes.com
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Yoga Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Adrenal Complex Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,994,00.html Adrenal Extract Source: Healthnotes, Inc.; www.healthnotes.com Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aloe Source: Healthnotes, Inc.; www.healthnotes.com Aloe Vera Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Amlodipine Source: Healthnotes, Inc.; www.healthnotes.com Anti-Inflammatory Drugs Source: Prima Communications, Inc.www.personalhealthzone.com Arctostaphylos Uva Ursi Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Bearberry Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Beargrape Alternative names: Uva Ursi Source: Integrative Medicine Communications; www.drkoop.com Bromelain Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Cascara Sagrada Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10013,00.html Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Alternative names: DHEA Source: Integrative Medicine Communications; www.drkoop.com DHEA Alternative names: Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Eicosapentaenoic Acid (EPA) Alternative names: EPA Source: Integrative Medicine Communications; www.drkoop.com EPA Alternative names: Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginseng (Panax) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10029,00.html
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Glycyrrhiza glabra Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Inhaled Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Ipriflavone Source: Prima Communications, Inc.www.personalhealthzone.com Jamaica Dogwood Alternative names: Piscidia erythrina, Piscidia piscipula Source: Integrative Medicine Communications; www.drkoop.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lotrisone Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html
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Mifepristone Source: Healthnotes, Inc.; www.healthnotes.com Mycolog II Source: Healthnotes, Inc.; www.healthnotes.com N-Acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Phosphatidylserine Source: Prima Communications, Inc.www.personalhealthzone.com Phosphatidylserine (PS) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html Piscidia Erythrina Source: Integrative Medicine Communications; www.drkoop.com Piscidia Piscipula Source: Integrative Medicine Communications; www.drkoop.com Plantago Major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Smilax Alternative names: Sarsaparilla; Smilax glabra Roxb. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Spanish Licorice Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Tobradex Source: Healthnotes, Inc.; www.healthnotes.com Topical Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Uva Ursi Alternative names: Arctostaphylos uva ursi Source: Integrative Medicine Communications; www.drkoop.com
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 CORTICOSTEROIDS Overview In this chapter, we will give you a bibliography on recent dissertations relating to corticosteroids. 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 “corticosteroids” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on corticosteroids, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Corticosteroids 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 corticosteroids. 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 developmental study of corticosteroids in plasma and adrenal glands of chick embryos by Kalliecharan, Rajdeo; PhD from DALHOUSIE UNIVERSITY (CANADA), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK24931
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Biopharmaceutical aspects of corticosteroid therapy in preterm infants by Arya, Vikram, PhD from UNIVERSITY OF FLORIDA, 2003, 77 pages http://wwwlib.umi.com/dissertations/fullcit/3117293
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Hair removal with the 3 msec Alexandrite laser in patients with skin types IV--VI: Efficacy, safety and the role of topical corticosteroids in preventing side effects by Aldraibi, Mohammed Saleh, ScD from BOSTON UNIVERSITY, 2003, 101 pages http://wwwlib.umi.com/dissertations/fullcit/3108132
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In vitro biosynthesis of corticosteroids from radiocholesterol and the effects of metopirone on various enzymatic reactions by Cheng, Su Chiau; ADVDEG from MCGILL UNIVERSITY (CANADA), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04577
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Mechanism of the cytolytic action of corticosteroids and its relationship to corticosteroid-resistance in malignant lymphocytes by Turnell, Roger William; PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK11267
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Studies on the action of corticosteroids on salmonid cells in culture by Lee, Lucila E. J; PhD from UNIVERSITY OF WATERLOO (CANADA), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL51975
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Studies on the metabolism of corticosteroids C-2l YL sulfates with particular reference to cortisol surface by Hall, Conrad St. George; ADVDEG from MCGILL UNIVERSITY (CANADA), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK09730
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The regulation and role of corticosteroids during fetal development by Tye, Lesley Margaret; PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK42770
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 CORTICOSTEROIDS 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 “corticosteroids” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on corticosteroids, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Corticosteroids By performing a patent search focusing on corticosteroids, 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. The following is an 8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on corticosteroids: •
Aqueous compositions containing corticosteroids for nasal and pulmonary delivery Inventor(s): Klyashchitsky; Boris (Newark, DE), Saidi; Zahir (Philadelphia, PA) Assignee(s): Elan Corporation plc (Dublin, IL) Patent Number: 6,241,969 Date filed: June 26, 1998 Abstract: The present invention provides compositions containing corticosteroid compounds as active agents for the treatment of ailments and diseases of the respiratory tract, particularly the lungs, by way of nasal and pulmonary administration. The corticosteroid compounds are present in a dissolved state in the compositions. The compositions can be formulated in a concentrated, essentially non-aqueous form for storage or in a diluted, aqueous-based form for ready delivery. In a preferred embodiment, the corticosteroid composition contains an ethoxylated derivative of vitamin E and/or a polyethylene glycol fatty acid ester as the high-HLB surfactant present in the formulation. The compositions are ideally suited for inhaled delivery with a nebulizer or for nasal delivery. Excerpt(s): The present invention relates to pulmonary drug delivery compositions useful for the inhaled administration of corticosteroid compounds and the method of their administration. The delivery compositions are useful for the treatment of ailments and diseases of the lungs. Similar corticosteroid compositions may be used for nasal delivery. Delivery of therapeutic compounds directly to affected lung tissues has several advantages. The drug reaches the target tissue without first entering the systemic circulation and being subjected to dilution by the blood, binding to blood components, or metabolism by the liver and excretion by the kidneys. A high local concentration of drug can be achieved in the lungs while the systemic concentration is kept below that likely to cause adverse side effects. In addition, the apical side of the lung tissue--the side exposed directly to inspired air--can be treated with compounds that might not readily cross the endothelium or epithelium, which form barriers between the apical surface and the blood plasma. Similar considerations apply to the tissues lining the nasal passages and sinus cavities. Several means have been developed to deliver compounds directly to the passages of the lung or nose. The most common form, especially for water-insoluble drugs, is a powder suspension that is propelled into the mouth while the patient inhales. Web site: http://www.delphion.com/details?pn=US06241969__
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Artificial antibodies to corticosteroids prepared by molecular imprinting Inventor(s): Mosbach; Klaus (Lackalaenga 31, S-244 94, Furulund, SE), Ramstrom; Olof (Kallarekroken 64, S-226 37, Lund, SE) Assignee(s): none reported Patent Number: 6,255,461 Date filed: April 5, 1996 Abstract: The invention relates to artificial antibodies that are prepared by molecular imprinting, where methacrylic acid, ethylene glycol dimethacrylate and a print molecule
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are combined to form an artificial antibody having spatially positioned binding sites dictated by the corticosteroid print molecule, and the antibodies can be used in separation and analytical procedures. Excerpt(s): The present invention relates to artificial antibodies that selectively recognize steroids and act as antibody and receptor binding mimics. More specifically, the present invention relates to molecularly imprinted polymers (MIPs) that selectively recognize cortisol and corticosterone based steroids, their preparation and use in analyses, therapies and separation procedures. Molecular imprinting is a technique devised to generate a polymeric material that is analyte specific. The analyte can be any organic molecule, biological or macromolecule. Molecular imprinting has been used to prepare materials that recognize proteins or other biological compounds, especially where the structural information needed for rational design is lacking. Likewise, if a natural receptor is poorly characterized or difficult to isolate, artificially prepared mimics may serve as a useful alternative. Furthermore, such polymers are considerably less costly to produce when compared to, e.g., antibodies and receptors. Antibodies are used in several areas, such as therapy, immunoaffinity and purification. Of particular interest is the use of antibodies in immunoassays. However, antibodies for these procedures are normally produced by immunizing animals with the corresponding antigen leading to polyclonal antibodies, or by using fused cells (B cells) allowing the obtained cell lines to produce monoclonal antibodies. Web site: http://www.delphion.com/details?pn=US06255461__ •
Composition of pyruvate and anti-cortisol compounds and method for increasing protein concentration in a mammal Inventor(s): Beale; Paxton K. (1801 Bush St., Suite 300, San Francisco, CA 94109) Assignee(s): none reported Patent Number: 5,756,469 Date filed: July 26, 1996 Abstract: The present invention is based, in part, upon the discovery that the use of pyruvate in combination with a cortisol blocker, such as phosphatidylserine, produces a synergistic effect in increasing lean body mass or muscle tissue, decreasing fat deposition, increasing endurance and athletic performance of a mammal consuming same. The invention also relates to a method of treating the catabolic effects of diseases such as cancer and AIDS by the administration of pyruvate and a cortisol blocker.The present invention also discloses a synergistic composition comprising pyruvate and a cortisol blocker. More specifically, the present invention relates to a composition which comprises pyruvate and/or derivatives of pyruvate and phosphatidylserine. Excerpt(s): The present invention relates generally to a composition for enhancing the protein concentration or muscle mass of a mammal and a method for enhancing the protein concentration or muscle mass in a mammal. More specifically, the present invention relates to a composition which comprises pyruvate and/or derivatives of pyruvate and an anti-cortisol or cortisol blocker compound. The method of the present invention comprises administering to a mammal in need of enhancing its protein concentration or muscle mass, a composition comprising pyruvate and an anti-cortisol compound. Athletes engage in strenuous training to accomplish the goals of their sport. This strenuous training essentially amounts to trauma to the body, in that the human body interprets every strenuous work-out as a threat to its survival. It is known that
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muscle damage, caused by training, releases the catabolic hormone prostaglandin-E2. Training also causes the release of adrenocorticotropin (ACTH), which is a pituitary hormone. The presence of increased levels of ACTH increases the production of the catabolic hormone cortisol. Cortisol is also known as hydrocortisone, which is a glucocorticoid of the adrenal cortex that is a derivative of cortisone and is used in the treatment of rheumatoid arthritis. Thus, cortisol is a naturally occurring antiinflammatory steroid. This catabolic hormone results in the release of amino acids from muscle tissue and prevents absorption of glucose. Cortisol, as a catabolic stress hormone, cannibalizes muscle tissue. High cortisol levels also result in the breakdown of connective tissue, lowered immunity and reduced muscle RNA synthesis. While cortisol may be a detriment to the athlete, scientists have conjectured that when the human body is stressed or traumatized, it triggers a "fight or flight" survival response. The biological design of cortisol is such that when a human is threatened, cortisol levels rise and mobilize the body for action by breaking down fat and muscle stores for emergency energy. Cortisol also reduces swelling in the event of injury. After the threat or trauma has subsided, cortisol levels return to normal. The cortisol-stress relationship is designed for intermittent physical threats and not the constant stimulation provided by today's aggressive athletes. Ongoing training results in cortisol levels that do not return to normal for extended periods of time and thereby result in the breakdown or loss of muscle tissue. In order to reduce the catabolic effect of prolonged, intense training, a cortisol antagonist or blocker would be beneficial to the athlete. As used herein and in the claims, the term "cortisol blocker" means any known chemical entity that, when administered to an animal, will retard or prevent the production of cortisol or inhibit or prevent the catabolic activity of cortisol against muscle tissue. Web site: http://www.delphion.com/details?pn=US05756469__ •
Compositions containing corticosteroids or analogues thereof and corticosteroid buffering effective amounts of 5-androstene 3B, 17B or 5-androstene 3B, 7B, 17B triol or analogues thereof Inventor(s): Loria; Roger M. (3819 Brook Rd., Richmond, VA 23227) Assignee(s): none reported Patent Number: 5,387,583 Date filed: April 20, 1993 Abstract: 3.beta.,17.beta.-androstenediol (".beta.AED") and 3.beta.,7.beta.,17.beta.androstenetriol (".beta.AET") may be used to counteract the antiproliferative and immunosuppressive effects of hydrocortisone and other corticosteroids (i.e., to act as buffers to counteract the lymphosuppressive response to such steroids).beta.AED and.beta.AET are steroids which mediate immune response to provide the body protection against immune down-regulation. A method for testing analogues of.beta.AED and.beta.AET to compare the effectiveness of such analogues as buffers of certain effects of hydrocortisone and other corticosteroids, including immune response and proliferative effects is described. Cytokines, including most particularly IL-3, are produced by addition of.beta.AET and.beta.AED and their analogues to the growth media of cell cultures of lymphatic cells. Excerpt(s): This invention relates to 3.beta.,17.beta.-androstenediol (".beta.AED") and 3.beta.,7.beta.,17.beta.-androstenetriol (".beta.AET") and their use to counteract the antiproliferative and immunosuppressive effects of hydrocortisone and other corticosteroids (i.e., to act as buffers to counteract the lymphosuppressive response to
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such steroids).beta.AED and.beta.AET act as immune regulating steroids in the body. By "immune regulating steroids" is meant steroids which mediate immune response to provide the body protection against immune down-regulation. The invention also relates to means for testing analogues of.beta.AED and.beta.AET to compare the effectiveness of such analogues as buffers of certain effects of hydrocortisone and other corticosteroids, including immune response and proliferative effects. Finally the invention relates to production of cytokines, including most particularly IL-3, by addition of.beta.AET and.beta.AED and their analogues to the growth media of cell cultures of lymphatic cells. In vertebrates the development of host protection against pathogens requires a selective host immune response that involves the mobilization of the humoral and/or cellular mediated immune responses. Several factors adversely affect the body's protective response capability by causing prolonged immunosuppression or "down-regulation" of the immune system. It is, in reality, more appropriate to speak of "mal-regulation" or "deregulation" of the immune system than of down-regulation since the result is a failure to protect the body from assault. Immunosuppression provides an opportunity for pathogens to grow in the host. It does not matter what causes the primary insult to immunity. The resulting inability to muster the appropriate immune response has the same effect. Among the many different causes of immuno-suppression are viral, bacterial, fungal, yeast and parasitic infections, chemotherapy, irradiation, severe stress, chronic fatigue syndrome, diabetes mellitus, autoimmune diseases, rheumatoid arthritis and some forms of steroid therapy. Clinically, DHEA has been used systemically and/or topically for treating patients suffering from psoriasis, gout, hyperlipemia, and it has been administered to postcoronary patients. (W. Regelson et al., New York Academy of Sciences, 518, 260-273 (1988)). In mammals DHEA has been shown to have weight optimizing and anticarcinogenic effects. Web site: http://www.delphion.com/details?pn=US05387583__ •
Compositions for the treatment of warts and herpes Inventor(s): Konstantinovic; Predrag (376 Trinity La., Oakbrook, IL 60521), Wise; Ronald D. (9037 Kildare Ave., Skokie, IL 60076) Assignee(s): none reported Patent Number: 5,977,176 Date filed: November 19, 1996 Abstract: Compositions comprising propolis, propolis and salicylic acid, or propolis and either a corticorsteroid such as hydrocortisone or a halogenated corticosteroid with or without salicylic acid, are effective in the treatment of warts and in the treatment of herpesviruses. Compositions with corticosteroids are more effective than propolis alone because they reduce inflammation associated with viruses causing warts or herpes eruptions. Excerpt(s): Topical application of propolis is an effective, non-invasive, painless treatment against warts. Mixing propolis with salicylic acid, hydrocortisone or both results in a synergistic effect, achieving a faster resolution of warts compared to results obtained by applying either propolis or salicylic acid. Hydrocortisone reduces inflammation. Propolis compositions are also effective against herpes infections. Warts are a widespread medical problem that cause pain and discomfort, and may lead to complications if untreated or improperly treated. Warts are benign growths of the skin caused by a virus that involves the epidermis. Five different types of warts are classified
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by their clinical presentation. (1) verrucae vulgares are common warts that display hyperkeratosis and may occur anywhere except the genital and mucous membranes and plantar surfaces (soles of the feet); (2) verrucae planae are flat warts that usually occur on the face, trunk and extremities; (3) verrucae plantares are warts that occur only on the soles of the feet; (4) condylomata acuminata are venereal warts that occur on the genitals and mucous membranes; (5) premalignant warts (epidermoldysplasia verruciformis) usually occur on the hands and feet and are rare in occurrence. Wart treatment is not satisfactory. Many treatments of verrucae involve physical destruction of the infected cells. Choice of treatment depends on the location, size, number, type of wart, age and co-operation of the patient. No one treatment modality is uniformly effective. Web site: http://www.delphion.com/details?pn=US05977176__ •
Cyclodextrins as suspending agents for pharmaceutical suspensions Inventor(s): Guy; Yaacov J. (Rehovot, IL) Assignee(s): Pharmos Corporation (New York, NY) Patent Number: 5,576,311 Date filed: November 30, 1994 Abstract: The present invention relates to stable aqueous suspension of drugs suitable for therapeutic administration without requiring solubilization or complexation of those drugs. The suspensions are stabilized with cyclodextrin type suspending agents. Stabilized suspensions of corticosteroids which employ these suspending agents are useful for therapeutic treatment of the eye, ear, or nose. Excerpt(s): The invention relates to stable aqueous suspensions of poorly water soluble drugs for treatment of ophthalmic and otolaryngological inflammations or any other conditions requiring use of a drug in a suspension. Numerous drugs are prepared in the form of suspensions for ophthalmic, oral, otic, nasal and respiratory topical applications. Formulation of pharmaceutical dosages of water-insoluble drugs as suspensions is frequently hampered by the subsequent formation of cakes resulting from aggregation of the suspended material. Polymeric compounds (e.g. polyvinyl pyrrolidone ("PVP"), polyvinyl alcohol ("PVA"), and dextran are commonly used to stabilize such suspensions. An alternative approach to the preparation of such drugs is to enhance the solubility of the drugs within the formulation by vehicles such as emulsions, liposomes, and cyclodextrins. However, certain drugs, in their therapeutic concentrations, are not sufficiently stabilized or solubilized by these methods for the above-mentioned applications. Generally, a variety of cyclodextrins have been used to solubilize poorly water-soluble or water-insoluble drugs and to stabilize drugs which are unstable in water in the form of inclusion complexes. The present invention relates to the entirely novel use of modified cyclodextrins to stabilize and facilitate the formation of aqueous suspensions of particulate water-insoluble drugs. Web site: http://www.delphion.com/details?pn=US05576311__
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DNA encoding variants of human corticosteroid binding globulin Inventor(s): Avvakumov; George V. (London, CA), Hammond; Geoffrey L. (Lambeth, CA) Assignee(s): Allelix Biopharmaceuticals Inc. (Mississauga, CA) Patent Number: 5,432,080 Date filed: December 16, 1992 Abstract: A novel steroid-binding variant of human corticosteroid binding globulin in which one or more of the glycosylation sites, other than the glycosylation site at amino acid position 238, has been functionally disrupted is complexed with an antiinflammatory ligand in the treatment of inflammation in mammals. Excerpt(s): The present invention relates to corticosteroid binding globulin. In particular, the present invention relates to variants of corticosteroid binding globulin, their production via recombinant DNA-based techniques and their use in the treatment of inflammation. Corticosteroid binding globulin, hereinafter referred to as "CBG", is a plasma glycoprotein having a high affinity for endogenous glucocorticoids. CBG functions to regulate the biological activity of glucocorticoids in vivo. The binding of glucocorticoids to CBG is believed to reduce the metabolic clearance rate of glucocorticoids from plasma, thereby increasing their biological half-life. Many glucocorticoids such as steroid hormones exhibit anti-inflammatory properties. Upon binding with CBG, glucocorticoids become biologically inactivated and, thus, do not exert anti-inflammatory action. However, at sites of inflammation where glucocorticoid activity is required, glucocorticoids are enzymatically released from their CBG-bound form to assume their free active form in which they function in the capacity of an antiinflammatory agent. As a result of its high affinity for steroid hormones and its function in the transport of bound steroids to sites of inflammation, CBG has been found to be useful in the therapeutic treatment of inflammation by serving as a vehicle for the delivery of anti-inflammatory agents to sites of inflammation in mammals. This use has been described in U.S. Pat. Nos. 4,997,814 and 5,086,039, both of which are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05432080__
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Drug delivery compositions for improved stability of steroids Inventor(s): Ebert; Charles D. (Salt Lake City, UT), Jain; Uday (Salt Lake City, UT), Venkateshwaran; Srinivasan (Salt Lake City, UT) Assignee(s): Theratech, Inc. (Salt Lake City, UT) Patent Number: 5,780,050 Date filed: July 20, 1995 Abstract: A stabilized patch device for transdermal drug delivery of steroid drugs containing a 3-keto-4-en functional group is described, wherein the patch comprises an effective amount of the steroid drug and a carrier that is free of acid functional groups. The device can further contain additives such as a penetration enhancer or excipient, so long as such additives are also free of acid functional groups. The device can be either a matrix patch or a liquid reservoir patch. In a matrix patch, the carrier is a biocompatible polymeric adhesive with which the steroid drug is intimately admixed. The adhesive is preferably an acrylic polymer or copolymer. In a liquid reservoir patch, the carrier is a
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controlled-viscosity composition containing a thinner or thickener. Preferred steroid drugs include certain corticosteroids and sex hormones, such as progestins and androgens. A method of stabilizing such steroid drugs during storage in transdermal patches is also disclosed. Excerpt(s): This invention relates generally to drug delivery compositions for stabilizing steroid drugs having a 3-keto-4-en functional group in the A ring of the steroid. More particularly, the invention relates to stabilized patch devices for transdermal delivery of such steroid drugs and methods of stabilizing steroid drugs during storage in transdermal drug delivery devices. Steroids having the 3-keto-4-en functional group include certain sex hormones and certain adrenocortical hormones (corticosteroids). The corticosteroids have numerous and diversified physiological functions and pharmacological effects. They influence carbohydrate, protein, fat, and purine metabolism; electrolyte and water balance; and the functions of the cardiovascular system, the kidney, skeletal muscle, nervous system, and other organs and tissues. Therapeutically, the corticosteroids are used for treating hormonal insufficiencies, inflammation, and other conditions, whereas the sex hormones are widely used for contraception and hormonal insufficiencies, as well as for treating other conditions. Progesterone is secreted by the ovary, mainly from the corpus luteum, during the second half of the menstrual cycle. Abrupt decline in the release of progesterone from the corpus luteum at the end of the cycle is the main determinant of the onset of menstruation. The sequence of changes in the endometrium, brought about by progesterone during the luteal phase of the cycle and leading to the secretory endometrium, is well known. The endocervical glands are also influenced by progesterone. Further, the estrogen-induced maturation of the human vaginal epithelium is modified toward the condition of pregnancy by the action of progesterone, and the phenomenon of a rise in body temperature that correlates with the event of ovulation is caused by progesterone. During pregnancy, the developing placenta begins to secrete progesterone, and large amounts of progesterone are secreted up to the time of delivery. Also during pregnancy, and to a minor degree during the luteal phase of the cycle, progesterone, acting with estrogen, brings about a proliferation of the acini of the mammary gland. Toward the end of pregnancy, the acini fill with secretion and the vasculature of the gland is notably increased; however, only after the influences of estrogen and progesterone are withdrawn by parturition does lactation begin. Web site: http://www.delphion.com/details?pn=US05780050__ •
Ear and skin cleanser Inventor(s): Melman; Steven A. (8909 Iverleigh Ct., Potomac, MD 20854) Assignee(s): none reported Patent Number: 5,480,658 Date filed: July 23, 1993 Abstract: The present invention relates to a preferably pH balanced multi-purpose cleaning solution containing acetic acid and boric acid in a water base, useful on pets for the routine cleaning of the ear, the cleaning of the sensitive ear, particularly for cleaning moist, waxy or odiferous ears, the prevention and treatment of ear disease such as Swimmer's Ear and other ear diseases, acidification of the ear, and wound cleaning. The claimed solution may also contain a topical anesthetic, such as lidocaine hydrochloride, to provide relief from pain during treatment, and may be used as a carrier material for topical applications of medications including antibiotics and corticosteroids.
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Excerpt(s): The present invention relates to an acetic acid and boric acid multi-purpose cleansing solution for use on pets. Emphasis is on the usefulness of the solution for the routine cleaning of the ear, the cleaning of the sensitive ear, particularly for cleaning moist, waxy or odiferous ears, the prevention and treatment of ear disease, acidification of the ear, and wound cleaning. The solution may also be combined with a topical anesthetic to provide relief from pain caused by irritation, redness, swelling and lesions while the ear or skin is being treated. Additionally, the solution may be used as a carrier for topical applications of medications including corticosteroids and antibiotics. Keeping pet's ears clean and free from infection and parasites has always been a problem for pet owners, groomers and veterinarians, partially because the structure of most pet ears do not allow access for cleaning, especially if the pet is uncooperative because of an already irritated ear. Additionally, as the structure of the ear canal of pets are convoluted and inverted and are not self-cleaning or draining, and naturally produce oils and lipids, or fatty acids, and wax, collectively called cerumen, they are prone to becoming irritated because of wax build-up, excessive moisture or yeast infections. Swimmer's Ear is an example of a common affectation of the ear caused by excessive moisture whereby a swimmer receives contaminated water in the ear or overly moisturizes (macerates) the ear causing it to succumb to microbial growth (most often pseudomonas). Other factors present in certain breeds of dogs, such as hair in the ears (poodles, terriers), pendulous ears (spaniels), or narrow vertical canal and/or folded pinna (sharpei), further predisposes the ear to ear disease and increases the risk of ear disease. Web site: http://www.delphion.com/details?pn=US05480658__ •
Immunoassay and monoclonal antibodies for urinary cortisol Inventor(s): Barrande; Christophe (Marseilles, FR), Cuilleron; Yves-Claude (Ste Foy les Lyon, FR), Fournier; Catherine (Villeurbanne, FR), Lupi-Chen; Nina (Marseilles, FR), Mappus; Elisabeth (Ste Foy les Lyon, FR), Portuesi; Sandrine (Marseilles, FR) Assignee(s): Immunotech (Marseille, FR), Inserm (Paris, FR) Patent Number: 5,910,575 Date filed: March 22, 1996 Abstract: A polyclonal or monoclonal antibody recognizing specifically cortisol in a urine medium produced by immunization of animals against an immunogen compound composed of the hapten cortisol-3-carboxymethyloxime (syn isomer), coupled by its carboxyl function to a macromolecule, an immunoasay process for cortisol, particularly urinary cortisol, an assay kit and novel derivatives of coritsol. Excerpt(s): The present invention relates to a new immunoassay process for cortisol involving neither extraction nor chromatography, based on the surprising properties of certain antibodies directed against cortisol. The invention provides in particular the antibodies themselves, a process for obtaining them, assay processes for cortisol based on these antibodies, and kits of reagents allowing the use of said processes. Cortisol, the principal glucocorticoid hormone, is synthesized in the fascicular and reticular zones of the adrenal cortex. It is derived from cholesterol under the influence of several enzymes. Its rate of secretion is under hypothalamic-pituitary control. CRF (Corticotropin Releasing Factor) activates the anterior pituitary which produces ACTH, which in turn stimulates the adrenal cortex which synthesizes corticoids, of which 90% is cortisol. In the plasma, the majority of the cortisol circulates in the form bound to plasma proteins:
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mainly to corticosteroid binding globulin, to albumin and to testosterone estradiol binding globulin; a very small proportion exists in the free form. Web site: http://www.delphion.com/details?pn=US05910575__ •
Method for the treatment of corticosteroid induced osteopenia comprising administration of modified PTH or PTHrp Inventor(s): Vickery; Brian H. (Mountain View, CA) Assignee(s): Syntex (U.S.A.) Inc. (Palo Alto, CA) Patent Number: 5,821,225 Date filed: June 7, 1995 Abstract: Synthetic polypeptide analogs of parathyroid hormone PTH, parathyroid hormone related peptide PTHrp, and of the physiologically active truncated homologs and analogs of PTH and PTHrp, in which amino acid residues (22-31) form an amphipathic.alpha.-helix, said residues (22-31) selected from hydrophilic amino acids (Haa) and lipophilic amino acids (Laa) ordered in the sequence:Haa(Laa Laa Haa Haa).sub.2 Laaand their pharmaceutically acceptable salts are useful for the prophylaxis and treatment of corticosteroid induced osteopenia in mammals. Excerpt(s): This invention relates to methods for the treatment of corticosteroid induced osteopenia via the administration of therapeutically effective amounts of certain novel analogs of parathyroid hormone and parathyroid hormone related peptide. Osteoporosis is the most common form of metabolic bone disease and may be considered the symptomatic, fracture stage of bone loss (osteopenia). Although osteoporosis may occur secondary to a number of underlying diseases, 90% of all cases appear to be idiopathic. Postmenopausal women are particularly at risk for idiopathic osteoporosis (postmenopausal or Type I osteoporosis). Another high risk group for idiopathic osteoporosis is the elderly of either sex (senile or Type II osteoporosis). Osteoporosis has also been related to corticosteroid use, immobilization or extended bed rest, alcoholism, diabetes, gonadotoxic chemotherapy, hyperprolactinemia, anorexia nervosa, primary and secondary amenorrhea, and oophorectomy. In the various forms of osteoporosis, bone fractures, which are the result of bone loss that has reached the point of mechanical failure, frequently occur. Postmenopausal osteoporosis is characterized by fractures of the wrist and spine, while femoral neck fractures seem to be the dominant feature of senile osteoporosis. Web site: http://www.delphion.com/details?pn=US05821225__
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Method of pretreating an animal with a corticosteroid prior to infusion of a perfluorochemical emulsion Inventor(s): Goodin; Thomas H. (Manchester, MO), Kaufman; Robert J. (University City, MO) Assignee(s): HemaGen/PFC (St. Louis, MO) Patent Number: 5,670,495 Date filed: April 25, 1996 Abstract: This invention is directed to a method of attenuating or preventing the adverse side-effects of a perfluorochemical (PFC) emulsion on the hemostatic system and serum
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chemistry of an animal. The method includes intravenously administering a corticosteroid to an animal prior to intravenous administration of a PFC emulsion, in an amount sufficient to improve the adverse effects of the PFC upon the hemostatic system and serum triglyceride/enzyme levels of the animal. After administration of the corticosteroid, the PFC emulsion is administered intravenously. Preferably, the corticosteroid is dexamethasone, and the PFC is perfluorodichlorooctane. Excerpt(s): This invention is directed to the use of corticosteroids, and more particularly, to the use of corticosteroids for reducing or attenuating the adverse effects of a perfluorochemical emulsion on the hemostatic system and serum chemistry parameters of an animal. Perfluorochemical (PFC) emulsions are being developed for many different uses. Because PFCs have a high intrinsic solubility for gases, including O.sub.2 and CO.sub.2, they are especially useful as O.sub.2 /CO.sub.2 transport agents, artificial bloods, and red blood cell substitutes. PFC emulsions also are being developed as contrast agents for biological imaging. However, one of the drawbacks in using PFC emulsions in animals is that these emulsions produce certain undesirable side effects. Side effects from the intravenous infusion of a PFC emulsion have been reported in both human and animal studies. Two groups of side effects have been observed in human volunteers receiving a perfluorooctylbromide (PFOB) emulsion. PFOB, also known as Perflubron, is a PFC under development as a component of a blood-pool imaging agent known as Imagent BP. Imagent BP is a phospholipid emulsion containing ninety (90%) percent w/v Perflubron and having a mass median particle size of approximately 0.2.mu. The first group of side effects occurs within the first 2 hours after injection of the PFC emulsion. These acute effects are characterized primarily by skin flushing and backache. The second group of side effects occurs later than 2 hours post-injection and lasts generally for about a day. These delayed effects, described as a "flu-like syndrome", include fever, dizziness, and occasional nausea. S. F. Flaim, et al., "Characterization and Mechanism of Side Effects of Imagent BP (Highly Concentrated Fluorocarbon Emulsion) In Swine", Vol. 26, Investigative Radiology, November Supplement 1991, S122-S124. Web site: http://www.delphion.com/details?pn=US05670495__ •
Method of treating a skin disease with a corticosteroid-containing pharmaceutical composition Inventor(s): Baker; Anthony Richard (West Horsley, GB), Halls; Neil Graham (Glen Waverley, AU), Jones; Julie Irene (Herpenden, GB), Marriott; Peter (Grimsby, GB), Watmough; Peter (Grimsby, GB) Assignee(s): Medeva Europe PLC (London, GB) Patent Number: 6,126,920 Date filed: January 12, 1998 Abstract: Methods of treating various skin diseases, and in particular, scalp psoriasis, utilizing a foamable pharmaceutical composition comprising a corticosteroid active substance, a quick-break foaming agent, a propellant and a buffering agent are disclosed. The quick-break foaming agent typically comprises an aliphatic alcohol, water, a fatty alcohol and a surface active agent. Excerpt(s): The present invention relates to an improved composition for the topical application of corticosteroid active substances to the skin of a subject. Corticosteroids, particularly in the form of the ester compounds, are used, inter alia, in the treatment of skin diseases in humans, such as eczema, infantile eczema, atopic dermatitis, dermatitis
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herpetiformis, contact dermatitis, seborrhoeic dermatitis, neurodermatitis, psoriasis and intertrigo. Formulations containing such active substances have conventionally been applied to the skin site in the form of alcoholic solutions, lotions or creams. However, there is a high degree of ineffectiveness with such formulations. Lotions and creams are generally too viscous to allow efficient penetration of the active substance to the epidermis, and solutions have a tendency to evaporate before penetrating the epidermis. In addition, conventional cream bases are irritating to the skin, particularly over the often long exposure that is required, and the fluidity of lotions often makes the physical application difficult to control. Moreover, it is necessary to rub such formulations into the target site to improve the penetration of the active substance into the epidermis, an action which itself produces irritation. There has therefore been a very real need in the treatment of skin disorders requiring treatment with corticosteroids for improved formulations which target the most effective corticosteroid to the skin site with improved delivery of active, substance with decreased inconvenience and irritation, and increased ease of use for the patient. Web site: http://www.delphion.com/details?pn=US06126920__ •
Method of treating warts using tazarotene Inventor(s): Da Silva; Luiz B. (1995 Camino Ramon Pl., Danville, CA 94526), Weber; Michael R. (13906 Term La., Clearwater, FL 33762), Weber; Paul J. (1 Seneca Rd., Ft. Lauderdale, FL 33308) Assignee(s): none reported Patent Number: 6,114,348 Date filed: March 10, 1999 Abstract: A method and composition for topically treating non-metastasizing skin eruptions of warts with tazarotene in a suitable pharmaceutical composition. The compositions can include corticosteroids or fluorouracil. Excerpt(s): The present invention relates to a method of treating certain nonmetastasizing skin eruptions. More particularly, there is provided a method of treating warts and keratoacanthoma with a composition containing ethyl 6-[2-(4,4dimethylthiochroman-6-yl)--ethynyl]nicotinate (Tazarotene) or the salts thereof. Warts are benign tumors that commonly involve skin and less frequently affect other epithelial tissues. These lesions are induced by papillomaviruses which are deoxyribonucleic acid (DNA)-containing viruses. The approach to treatment of warts depends on the age of the patient, the extent and duration of lesions and the patient's immunological status. Common therapy has been cryotherapy, using caustics and acids such as salicylic acid, lactic acid, trichloracetic acid or retinoic acid. Unfortunately, many warts resist such treatment, especially in organ transplant patients. Keratoacanthoma is a common keratinizing cutaneous squamous neoplasm characterized by rapid and prolific growth sometimes followed by spontaneous involution, classically occurring on the sunexposed skin of elderly light skinned individuals. There are several methods of treating keratoacanthomas. Surgical excision and injectable intralesional 5-fluorouracil have been used to remove lesions, but scarring occurs from surgery and necrosis of tissue occurs. 5-Fluorouracil has been used for solitary, multiple and large lesions. This treatment requires painful injections and needs to be complete to be effective. Corticosteroids have been used with variable success. Web site: http://www.delphion.com/details?pn=US06114348__
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Methods and compositions for modulating responsiveness to corticosteroids Inventor(s): Banerjee; Subhashis (Shrewsbury, MA), Carter; Adam (Newburyport, MA), Ghayur; Tariq (Grafton, MA), Sekut; Les (Westborough, MA), Tracey; Daniel E. (Harvard, MA) Assignee(s): BASF Aktiengesellschaft (Rheinland Pfalz, DE) Patent Number: 6,054,487 Date filed: March 18, 1997 Abstract: Method for modulating responsiveness to corticosteroids in a subject are provided. In the method of the invention, an agent which antagonizes a factor that regulates production of IFN-.gamma. in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an interferon-.gamma. inducing factor (IGIF) antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a factor that regulates production of IFN-.gamma. in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceutically acceptable carrier. Excerpt(s): Standard therapy for a variety of immune and inflammatory disorders includes administration of corticosteroids, which have the ability to suppress immunologic and inflammatory responses. Corticosteroids are used in the treatment of disorders such as asthma, autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus) and transplant rejection (for reviews on corticosteroids, see e.g., Truhan, A. P. et al. (1989) Annals of Allergy 62:375-391; Baxter, J. D. (1992) Hospital Practice 27:111-134; Kimberly, R. P. (1992) Curr. Opin. Rheumatol. 4:325-331; Weisman, M. H. (1995) Curr. Opin. Rheumatol. 7:183-190). Corticosteroids are also used topically in the treatment of various dermatological disorders, such as contact dermatitis, psoriasis vulgaris, lichen planus, keloids and urticaria pigmentosa (for a review, see Sterry, W. (1992) Arch. Dermatol. Res. 284 (Suppl.):S27-S29). While therapeutically beneficial, the use of corticosteroids is associated with a number of side effects, ranging from mild to possibly life threatening. Complications associated with prolonged and/or high dose steroid usage include musculoskeletal effects (e.g., osteoporosis, myopathy, aseptic necrosis of bone), ophthalmic effects (e.g., posterior subcapsular cataracts), gastrointestinal effects (e.g., ulcers, pancreatitis, nausea, vomiting), cardiovascular effects (e.g., hypertension, atherosclerosis), central nervous system effects (e.g., pseudotumor cerebri, psychiatric reactions), dermatological effects (e.g., hirsutism, redistribution of subcutaneous fat, impaired wound healing, thinning of the skin) and suppression of the hypothalamus-pituitary-adrenal axis (see e.g., Truhan, A. P. et al. (1989) Annals of Allergy 62:375-391). Many of the side effects of corticosteroid usage appear to be dose-dependent (Kimberly, R. P. (1992) Curr. Opin. Rheumatol. 4:325-331). Accordingly, methods and compositions that enable the use of a lower effective dosage of corticosteroids (referred to as the "steroid sparing effect") would be highly desirable to avoid unwanted side effects. Another problem that limits the usefulness of corticosteroids is the phenomenon of steroid resistance. Certain inflammatory or
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immunological diseases exhibit refractoriness to steroid treatment. For example, attempts to use corticosteroid therapy to treat septic shock in humans have met with disappointing results and thus corticosteroids are not generally recommended as adjunctive therapy in severe sepsis or septic shock (see e.g., Putterman, C. (1989) Israel J. Med. Sci. 25:332-338; Bone, R. C. and Brown, R. C. (1990) in Vincent, J. L. (ed.) "Update in Intensive Care and Emergency Medicine 10", Heidelberg:Springer Verlag, p. 121). Other disorders that often exhibit resistance to corticosteroid treatment include inflammatory bowel disease (see e.g., Hibi, T. et al. (1995) J. Gastroenterol. 30:121-123) and graft-versus-host disease (Antin, J. H. et al. (1994) Blood 84:1342-1348; Racadot, E. et al. (1995) Bone Marrow Transplantation 15:669-677). Thus, methods and compositions that can be used to overcome or reverse corticosteroid resistance in inflammatory and immunological disorders are still needed. Web site: http://www.delphion.com/details?pn=US06054487__ •
Methods and compositions for treating sinusitis, otitis media and other related disorders using antihistamines Inventor(s): Johnson; Nancy R. (Westfield, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,297,227 Date filed: September 9, 1999 Abstract: The present invention discloses antibiotic-excluded compositions and methods to treat non-infective sinusitis and otitis media. The compositions comprise a therapeutically effective amount of a corticosteroid, and the methods comprise administering a pharmaceutical composition comprising a therapeutically effective amount of a corticosteroid. Preferred corticosteroids are mometasone furoate and mometasone furoate monohydrate. Excerpt(s): The present invention generally relates to methods of treating sinusitis and otitis media (including otitis media with effusion and persistent middle ear effusion) involving the administration of a therapeutically effective amount of a corticosteroid. It specifically relates to such treatment involving the administration of a therapeutically effective amount of mometasone furoate. The subject matter of this patent application is related to that disclosed in pending U.S. patent applications, Ser. No. 09/391,795 filed of even date herewith, Ser. No. 08/376,506, filed Jan. 23, 1995, and Ser. No. 07/984,573, filed Apr. 29, 1998. Sinusitis is the most frequently reported chronic disease in the United States, affecting more than 14% of the population. Sinusitis is an inflammation of the mucosa of the paranasal sinuses. Generally, there is an allergic cause to sinusitis. Otitis media, like sinusitis, is also generally considered to have an allergic cause. These are also characterized by retention of thickened respiratory secretions; however, the inflammation is manifest in the ear rather than in the sinuses. A discussion of sinusitis and otitis media can be found in Conn's Current Therapy, 235 (1997); Diseases of the Sinuses--A Comprehensive Textbook of Diagnosis and Treatment, ed. M. E. Gershwin et al, Human Press, Totowa, N.J., pages 151-157 (1996); and Allergy--Principles and Practice, Volume II, ed. E. Middleton, Jr. et al, Mosby-Year Book, Inc., New York, pages 1027-1033 (1998). Also, a review of sinusitis and related facts is given by Z. Pelikan, "The Role of Allergy in Sinus Disease", Clinical Reviews in Allergy and Immunology, 16, 55156 (1998). Sinusitis and otitis media are often typically treated as infectious diseases. The treatment typically includes administration of an antibiotic along with a corticosteroid and an antihistamine, or a nasal decongestant. such as described in, for
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example, J. Braun et al, Allergy, 52 (6) 650-655 (1997). There are, however, occasions, when the sinusitis or otitis media is not necessarily accompanied by an infection. This is particularly true when the disease is associated with allergic rhinitis. At those times, administration of an antibiotic may not be needed. Physicians, however, do not generally administer corticosteroids for these indications without accompanying antibiotic. Web site: http://www.delphion.com/details?pn=US06297227__ •
Methods for prophylactic treatment of cardiovascular disease with inhibitor of cortisol synthesis Inventor(s): Marin; Per (Goteborg, SE) Assignee(s): Cortendo AB (Gothenburg, SE) Patent Number: 6,642,236 Date filed: November 14, 2000 Abstract: Ketoconazole and related substances which are inhibitors of cortisol synthesis can be administered to prophylactically treat cardiovascular disease, such as coronary artery disease, artiosclerotic manifestations, and stroke. Excerpt(s): The present invention relates to the use of ketoconazole or molecules resembling ketoconazole but with some side-chains, not affecting the biological activity compared to ketoconazole, changed for manufacturing drugs for treatment of diabetes mellitus type II. The drug ketoconazole (Trade name Fungora.TM.) is a welldocumented drug for treatment of fungal infections. The process of making ketoconazole is well known and described. In this invention Fungoral.TM. capsules aimed at oral administration should be used. This means that Fungoral.TM. should be administered the same way (oral) and in the same composition that is already wellknown on the market for treatment of fungal infections the oral route. Therefor it is not considered necessary to further describe the process of making Fungora.TM. For the same reason it is not considered necessary to give a full, clear, concise and exact term of this drug, since it is already well-known for persons skilled in the art of medicine. The drug comprising ketoconazole (Trade name Fungoral.TM.) and chemically closely related substances, the mode of operation of which is to influence the normal cortisol synthesis in the adrenal glands in such a way that the production of biologically perfectly acting cortisol is partly inhibited, is intended to be used for medical treatment of diabetes mellitus type II in men and women as well as for counter-acting the risk factors which are parts of the Metabolic Syndrome (also known as "the deadly quartet" or "Syndrome X" or the "Insulin Resistance Syndrome"), which is characterised by an accumulation of risk factors for cardiovascular disease, stroke and diabetes mellitus type II, i.e. insulin resistance, hyperinsulinemia, abdominal obesity, (caused by an accumulation of intra-abdominal fat), elevated serum lipids, and raised blood pressure, as well as reducing the risk of development of these diseases. Web site: http://www.delphion.com/details?pn=US06642236__
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Methods of inhibiting transplant rejecton in mammals using rapamycin and derivatives and prodrugs thereof Inventor(s): Calne; Sir Roy (22 Arrow Rd., Cambridge, GB2) Assignee(s): none reported Patent Number: 5,403,833 Date filed: February 7, 1994 Abstract: This invention provides a method of inhibiting organ or tissue transplant rejection in a mammal in need thereof, comprising administering to said mammal a transplant rejection inhibiting amount of rapamycin. Also disclosed is a method of inhibiting organ or tissue transplant rejection in a mammal in need thereof, comprising administering to said mammal (a) an amount of rapamycin in combination with (b) an amount of one or more other chemotherapeutic agents for inhibiting transplant rejection, e.g., azathioprine, corticosteroids, cyclosporin and FK506, said amounts of (a) and (b) together being effective to inhibit transplant rejection and to maintain inhibition of transplant rejection. Excerpt(s): This invention relates to methods of inhibiting organ or tissue transplant rejection in meals. More particularly, the invention relates to methods of inhibiting transplant rejection in meals in need thereof, comprising administering to such mammals a transplant rejection inhibiting amount of rapamycin. Rejection and infective complications resulting from immunosuppressive treatment are the principal causes of failure of organ allografting in man, that is, an organ graft made between two genetically different individuals in the same Homo saplens species. In order to minimize the individual specific side-effects of the three effective agents used in clinical practice, namely azathioprine, corticosteroids and cyclosporin, small doses of each are used in combination "triple therapy". Of the three agents currently used in such triple therapy, cyclosporin is the most powerful, but has the unsatisfactory side-effect of nephrotoxicity in man which can lead to structural renal damage. Increased corticosteroid dosage and antilymphocyte antibody preparations, poly- or monoclonal, are used for the treatment of rejection crises. A number of studies have been taken to investigate other potentially effective compounds for use as immunosuppressants and transplant rejection inhibitors, but to date, none have been found to be useful in clinical settings because of side-effects, such as toxicity, the lack of efficacy or a combination of these factors. The fungal product FK506 was reported to have immunosuppressive activity in animals with organ grafts (Ochiai, T., et al., Transplant. Proc., Vol. XX, No. 1, pp. 209-214, 1988). Although the immunosuppressive activity of FK506 was confirmed, the toxicity in mammals, such as rats, pigs and dogs, and in primates, e.g., baboons, was too severe to proceed to clinical phase trials (Collier, D. St. J., et al., Transslant. Proc., Vol. XX, No. 1, pp. 226-228, 1988). Web site: http://www.delphion.com/details?pn=US05403833__
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Methods of treating inflammatory dermatosis Inventor(s): Kligman; Albert M. (Philadelphia, PA) Assignee(s): none reported Patent Number: 5,998,395 Date filed: September 10, 1993
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Abstract: Inflammatory dermatoses are controlled and cleared by topical application to the affected areas of the skin of a composition containing both a corticosteroid and a retinoid. The combined therapy is more effective than either active ingredient alone and is particularly effective for chronic dermatoses which are or have become resistant to corticosteroid treatment alone. After clearing has been obtained with once or twice daily applications of the corticosteroid-retinoid composition, usually after several weeks, clearance can be maintained by less frequent application or lower concentrations of the composition or by application of only one of the corticosteroid or retinoid, less potent corticosteroids, or other non-steroidal therapies, depending upon the particular dermatosis being treated. Excerpt(s): The present invention relates to methods for the treatment of inflammatory dermatoses. More particularly, the invention is directed to controlling, clearing and maintaining the clearance of inflammatory dermatoses by administering topical compositions to the affected areas of the skin. The most widely prescribed drugs to treat dermatologic disease are corticosteroids, also known as glucocorticosteroids or glucocorticoids. Approximately 50% of prescriptions written by dermatologists are for topical corticosteroids. Since the introduction of these substances in the early 1950s for dermatologic diseases, topical corticosteroid therapy continues to be the mainstay for the management of a broad spectrum of inflammatory dermatoses. Although systemic corticosteroids are often required in some severe dermatologic diseases, topical treatment is preferred in most responsive cases because it causes fewer systemic adverse effects. Topical corticosteroids are generally effective in the treatment of acute and chronic dermatoses such as seborrheic dermatitis, atopic dermatitis, contact dermatitis of the irritant and allergic type, localized neurodermatitis (lichen simplex chronicus), lichen planus, and psoriasis. Steroids are also used for a variety of other less common conditions, such as Darier's disease and ichthyosiform dermatitis. A good overview of topical corticosteroid therapy appears in a series of papers presented at the Symposium on Topical Corticosteroids Today and Tomorrow, sponsored by Schering AG in Bali, Jun. 16-20, 1988, which were published in Drugs 36, Supplement 5, pp. 1-61 (Adis Press Ltd. 1988). Web site: http://www.delphion.com/details?pn=US05998395__ •
Non-preserved topical corticosteroid for treatment of dry eye, filamentary keratitis, and delayed tear clearance (or turnover) Inventor(s): Huang; Andrew J. W. (Miami, FL), Pflugfelder; Stephen C. (Miami, FL), Tseng; Scheffer C. G. (Miami, FL) Assignee(s): University of Miami (Miami, FL) Patent Number: 6,153,607 Date filed: December 4, 1996 Abstract: A preservative-free composition containing an effective amount of a corticosteroid in an aqueous carrier to treat a dry eye condition. The composition may be provided as a part of a therapeutic regimen to treat a variety of dry eye conditions and ocular surface disorders manifesting delayed tear clearance previously not readily treatable. The composition may be packaged as containers of single dosage amounts of the corticosteroid-aqueous composition sufficient for pulsed-therapy of acute exacerbations of the irritation symptoms and ocular surface disease of conditions associated with dry eye and delayed tear clearance.
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Excerpt(s): The invention relates to the field of pharmacology, in particular the treatment of dry eye syndrome and ocular surface disorders with delayed tear clearance using corticosteroid. A stable tear film ensures comfort and serves as the refractive optical surface of the eye. Furthermore, the tear film serves as a barrier for the ocular surface against microbial infection and inflammation from mechanical trauma.sup.1,2 Tear film deficiencies, referred to as dry eye, are a common clinical problem that can result from decreased secretion of tears by the lacrimal gland and/or increased evaporative loss due to a deficient lipid layer or blink abnormalities.sup.3 Patients with mild dry eye complain of annoying eye irritations. Those with severe dry eye, such as Sjogren's syndrome, may experience constant and disabling eye irritation, and develop ocular surface epithelial disease and sight-threatening sterile or microbial corneal ulceration.sup.4 The other reason that ocular irritation can occur is when the clearance of tears is delayed. Delayed tear clearance can be found in a number of other ocular surface disorders. Delayed tear clearance results in the accumulation of ocular irritants which can be derived from the environment (pollutants), medications (or preservatives), and cells (inflammatory mediators--to be described later). For years it has been recognized that patients with dry eye develop pathologic changes of the ocular surface epithelial cells termed squamous metaplasia. Unreported research suggests that this process is the result of increased proliferation, abnormal differentiation, and inflammation of the ocular surface epithelial cells. In contrast to normal cells, these metaplastic cells do not produce the mucus that normally coats the ocular surface and forms a barrier against infection and mechanical trauma. This renders the ocular surface susceptible to damage from the mild trauma of desiccation blinking, rubbing, and foreign bodies (such as contact lenses). Web site: http://www.delphion.com/details?pn=US06153607__ •
Preparation for the treatment of metabolic syndrome containing human growth hormone in combination with a cortisol synthesis inhibitor Inventor(s): M.ang.rin; Per (Goteborg, SE) Assignee(s): Cortendo AB (Vastra Frolunda, SE) Patent Number: 6,274,582 Date filed: August 24, 1999 Abstract: Human growth hormone is used in combination with a cortisol synthesis inhibitor, in particular ketoconazole, for prevention or treatment of conditions related to Metabolis Syndrome (Neuroendocrine Syndrome). Administration can be supplemented by a sex hormone selected from testosterone and natural or synthetic estrogen. Also disclosed are corresponding pharmaceutical compositions. Excerpt(s): The present invention relates to the prevention and treatment of Metabolic Syndrome. More particularly, the invention relates to medicaments, preparations and treatments comprising cortisol synthesis inhibitors and growth hormone for treating the conditions which comprise the Metabolic Syndrome. In both men and women, visceral (intra-abdominal) fat accumulation is associated with an increased risk of the development of non-insulin dependent diabetes, myocardial infarction, stroke and other arteriosclerotic diseases and their associated risk factors, including insulin resistance, elevated blood lipids, glucose and hypertension. The clustering of these risk factors has been designated `Metabolic Syndrome`, also called `Syndrome X`, the `Insulin Resistance Syndrome` or the `Deadly Quartet`. This syndrome is also characterised by one or more endocrine disturbances and is therefore also called `Neuro-endocrine
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Syndrome` (Marin, P. Neuroendocrine News, 21(3) 1996, 2). These disturbances include low serum levels of sex steroids (testosterone in men, and estrogens in women), signs of a decreased action of growth hormone, and an excessive secretion of cortisol. The latter has been shown clinically as a major causative process for the development of Metabolic Syndrome as demonstrated by successful treatment with the cortisol synthesis inhibitor ketoconazole (WO 96/04912). Conditions related to Metabolic Syndrome include diabetes mellitus type II (IDDM), non-insulin dependent diabetes (NIDDM), myocardial infarction, stroke and other arteriosclerotic diseases as well as the risk factors for these diseases, insulin resistance in general, abdominal obesity caused by accumulation of intra-abdominal fat, elevated serum lipids, and raised diastolic and/or systolic blood pressure. Web site: http://www.delphion.com/details?pn=US06274582__ •
Process for preparing delta 9,11 and 21-chloro corticosteroids Inventor(s): Colon; Cesar (Rahway, NJ), Fu; Xiaoyong (Edison, NJ), Lee; Junning (Gillette, NJ), Tann; Chou-Hong (Elizabeth, NJ), Thiruvengadam; Tiruvettipuram K. (Edison, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,502,222 Date filed: June 1, 1994 Abstract: Described is a process for the regioselective dehydration of 11-hydroxy steroids using PCl.sub.5, PCl.sub.3, POCl.sub.3 or either SO.sub. Cl.sub.2 and imidazole, or PPh.sub.3 and CCl.sub.4. The disclosed process selectively forms.increment.sup.9,11 steroids from either 11-.alpha.- or 11-.beta.-hydroxy steroids, and can also be used for the one-step conversion of 11,21-dihydroxy steroids to 21-chloro-.increment.sup.9,11 steroids. Excerpt(s): The synthesis of corticosteroids having therapeutic utility, such as mometasone, betamethasone and beclomethasone, requires functionalization of the C-9 and C-11 positions of the steroid molecule. The functionality is generally introduced via.increment.sup.9,11 steroid intermediates. Methods for preparing steroids having a 9,11 double bond are known in the art. For example, an 11-hydroxy steroid can be converted to the corresponding mesylate (by treating with mesyl chloride) which is transformed into a.increment.sup.9,11 steroid via an elimination reaction. However, the prior art methods are not regiospecific in the case of 11.alpha.-hydroxy steroids and typically lead to mixtures of.increment.sup.9,11 steroid containing 10-15% of the analogous.increment.sup.11,12 steroids. Separation of these regio-isomeric products is difficult, generally requiring laborious physical separation procedures, resulting in increased costs and lower yields. It would therefore be desirable to develop an efficient regioselective method for preparing.increment.sup.9,11 steroids, from either 11.alpha.or 11.beta.-hydroxy steroids, for use as intermediates in the synthesis of corticosteroids. The introduction of a 21-chloro group is also of commercial importance, e.g. for preparing intermediates and therapeutically important compounds such as mometasone. The conversion of 21-hydroxy steroids to the analogous 21-chloro steroid by chloride displacement of a 21-methanesulfonyl intermediate is known. However, this reaction is not regioselective in the case of 11-hydroxy steroids, as methanesulfonyl chloride reacts with both the 11- and 21-hydroxy groups. In addition, Wuts, et al., Syn. Comm., 23, (15) 2199-2211 (1993) describes a method for preparing 21-chloro steroids using the Vilsmeier reagent (prepared from DMF and POCl.sub.3 or phosgene).
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Reduced cortisol conjugates Inventor(s): Contestable; Paul B. (Rochester, NY), Groth; Holly L. (Hamlin, NY), Lynn; Shirley Y. (Rochester, NY), Snyder; Brian A. (Rochedster, NY), Sprague; Lisa D. (Naples, NY), Warren; Harold C. (Rush, NY) Assignee(s): Ortho-Clinical Diagnostics, Inc. (Rochester, NY) Patent Number: 6,383,766 Date filed: September 30, 1999 Abstract: The present invention relates to compositions comprising novel reduced cortisol conjugates, methods for their preparation and use in immunoassays for cortisol.In another aspect, it relates to conjugates of reduced cortisol as immunogens or haptens for eliciting anti-cortisol or anti-reduced cortisol antibodies. Excerpt(s): The present invention relates to haptens and conjugate labels having improved specificity for anti-cortisol antibodies, methods for their preparation and use in immunoassays for the detection of cortisol. More particularly, the present invention relates to conjugates comprising horseradish peroxidase and reduced cortisol. Cortisol is the major glucocorticoid in humans. It is synthesized and secreted by the zona fasciculata and the zona reticularis of the adrenal cortex. It is involved in the regulation of carbohydrate, protein, and lipid metabolism. Cortisol levels can rise ten fold following surgery or other major trauma, as the steroid acts to prevent vascular collapse, reduce inflammation, and suppress the immune system. There are three primary medical disorders associated with hyperadrenalism: Cushing's syndrome, hyperaldosteronism, and congenital adrenal hyperplasia. Cushing's syndrome is the term used to describe any condition resulting from an increased concentration of circulating glucocorticoid, usually cortisol (Clinical Chemistry: Theory, Analysis, and Correlation; Lawrence A. Kaplan, Amadeo J. Pesce, C V Mosby Company, 1989, pp 6734). Web site: http://www.delphion.com/details?pn=US06383766__
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Steroid intermediates and processes for their preparation Inventor(s): Andrews; David R. (Maplewood, NJ), Sudhakar; Anantha R. (East Brunswick, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 5,502,183 Date filed: July 25, 1994 Abstract: Novel steroids having a 9.alpha.-hydroxy or a 9.alpha.-carbonate substituent can be prepared from 9.alpha.-hydroxyandrostenedione and can be utilized in the synthesis of commercially valuable corticosteroids such as betamethasone. The 9.alpha.carbonates are prepared by reaction of the corresponding 9.alpha.-hydroxy steroid with a sequence of excess base, trialkylsilyl chloride, alkyl haloformate and alkanol or by using excess base, alkyl haloformate and alkoxide. 9.alpha.-Carbonate-17-keto compounds can be treated with lithium acetylide and a lithium salt to afford the corresponding 17.alpha.-ethynyl-17.beta.-hydroxy-9.alpha.-carbonate. This compound is
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then esterified with a novel series of reagents to give the 17-ester which can be reduced the corresponding 17-allene. Oxidation of this allene to the bis-epoxide compound, followed by treatment with an alkali metal salt of a carboxylic acid under phase transfer conditions gives the 17.alpha.-hydroxy 21-ester 9.alpha.-carbonate. Elimination of the 9.alpha.-carbonate group affords the a 17.alpha.-hydroxy, 9(11)ene, which in a few subsequent steps can be converted to a variety of commercially important corticosteroids. Novel 9.alpha.-carbonate compounds are prepared in the various reaction steps. Excerpt(s): The 9.alpha.-hydroxy steroids are known to be useful intermediates for preparing commercially valuable corticosteroids. These corticosteroids such as betamethasone find utility in the treatment of psoriasis, dermatological diseases and inflammation. U.S. Pat. No. 4,127,596 describes a process for dehydrating 9.alpha.hydroxysteroid type compounds with a strong acid (pKa less than 1) to give.DELTA.9,11 steroids. A.DELTA.9,11 steroid is one which possesses a double bond between positions 9 and 11 in the steroid ring. U.S. Pat. No. 4,102,907 and European Patent Application No. 87201933.6 teach dehydration of steroid intermediates. John Fried and John A. Edwards, Organic Reactions in Steroid Chemistry, Vol. II, Van Nostrand Reinhold Co., New York, N.Y. (1972), pp., 382-385; L. F. Fieser and M. Fieser, Steroids, Reinhold Publishing Corp., New York (1959), Chapter 18, Homo and Nor Steroids, pp. 577-599 and R. W. Draper and M. S. Puar Carbon-13 Nuclear Magnetic Resonance Spectra of D-homoannulated 17-hydroxypregnan-20-ones, Steroids 54/1, July, 1989, pp. 1-10, disclose undesirable D-ring homologation of 17-hydroxy-20-keto steroids by utilizing conventional acidic or alkaline reagents. J. Org. Chem., 44, pp. 15821584 (1979) notes that C-9.alpha. esters are not readily preparable. The.DELTA.9,11 steroids are useful intermediates for the preparation of pharmaceutically active corticosteroids as taught in L. F. Fieser and M. Fieser, Steroids, Chapter 19, Adrenocortical Hormones, pp. 600-726, supra, I. Nitta and H. Ueno, New Synthesis of Corticoids, Yuki Gosei Kagaku, Vol. 45, No. 5 (1987), pp. 445-461, and in J. Redpath and F. J. Zeelen, in Chem. Soc. Rev., Stereoselective Synthesis of Steroid Sidechains, Vol. 12 (1983), pp. 75-98. Thus, it would be desirable to provide a process for preparing.DELTA.9,11 steroids by dehydration of 9.alpha.-oxygenated steroids possessing the requisite 17,21-dihydroxy-20-ketone (corticoid) or 17-hydroxy-20-ketone (pregnane) side chain which avoids D-ring homo-rearrangement and which can also reduce the steps required for their preparation. The present invention utilizes a 9.alpha.carbonate of the 9.alpha.-hydroxy steroid as an intermediate in the synthesis of commercially valuable steroids. 9.alpha.-carbonates are prepared from the commercially available 9.alpha.-hydroxyandrost-4-ene-3,17-dione or its derivatives by a sequence of either excess base, trialkylsilyl halide, alkyl, vinyl, or phenyl haloformate and alkanol; or a sequence of excess base, excess alkylhaloformate and alkoxide. The use of the 9.alpha.carbonate allows for elimination in the presence of a 17-hydroxy group. h. treatment of the compound of step (g) with a strong acid to afford the.DELTA.9,11 steroid of formula I. Web site: http://www.delphion.com/details?pn=US05502183__
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Use of terpene compounds for reduced release of arachidonic acid and of inflammation mediators Inventor(s): Juergens; Uwe R. (Rheinallee 2, D-53859 Niederkassel, DE) Assignee(s): none reported Patent Number: 5,889,049 Date filed: February 23, 1995 Abstract: Disclosed is a method of treatment of steroid requiring inflammatory diseases using certain saturated monocyclic and bicyclic terpene compounds. These compounds may be administered in the form of capsules resistant to gastric juice, infusion solutions or intramuscular injection solutions. Because these particular terpene compounds exhibit steroid-like effects but without the harmful side-effects of conventional corticosteroids, the use of corticosteroids is substantially reduced, and in some cases, completely eliminated. Therefore, these terpene compounds are also suitable for longterm therapy and prophylaxis. Excerpt(s): The present invention relates to the use of saturated monocyclic or bicyclic terpenes for the treatment of inflammatory diseases. It is particularly concerned with the use of saturated monocyclic terpenes for the treatment of steroid-requiring inflammatory diseases exacerbated by infection, such as, for example, bronchial asthma. Acute and/or chronic inflammatory or acute allergic and/or chronic allergic inflammatory lesions are characterized by inflammatory infiltration of various organ systems by monocytes/macrophages, eosinophils, basophils and neutrophils, granulocytes, mast cells and thrombocytes. The degree of inflammatory activity correlates with the influence of these inflammatory cells in organ tissue, which causes damage to the organ concerned. These processes are a familiar feature in primary inflammatory diseases of the airways, the intestine and the articular cartilage in rheumatoid arthritis. Since the primary cause triggering most chronic inflammatory diseases is not known, these diseases can only be alleviated by nonspecific suppression of the inflammation stimulus. In an appropriate genetic predisposition or in the presence of environmental noxae, the reaction of the body to the exogenous noxae can be inhibited prophylactically by nonspecific suppression of the inflammation stimulus before the manifestation of disease symptoms. At the level of the cell, the further migration of inflammatory cells into an area of inflammation can be reduced by inhibiting chemotactic factors. This leads to the inflammatory activity subsiding with decline of the morphological and functional disorders of the organ system concerned, an effect which is typically mediated by immunosuppressants, e.g. corticosteroids. This group of agents is known to have an activity profile which comprises a strong antiinflammatory effect, but is only poorly tolerated since it causes severe side effects, namely osteoporosis, gastric and duodenal ulcers, steroid purpura or lymphopenia. Web site: http://www.delphion.com/details?pn=US05889049__
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Use of tetrahydrocortisol to prevent elevations in intraocular pressure caused by corticosteroids Inventor(s): Clark; Abbot F. (5708 Stage Line Dr., Arlington, TX 76017), Southren; Aaron L. (107 Grandview Ave., Monsey, NY 10952) Assignee(s): none reported Patent Number: 5,358,943 Date filed: February 2, 1993 Abstract: Pharmaceutical compositions useful in the treatment of ophthalmic inflammation and methods of treating ophthalmic inflammation with those compositions are disclosed. The compositions contain a combination of a glucocorticoid and tetrahydrocortisol. The tetrahydrocortisol serves to substantially prevent any significant increases in intraocular pressure which might otherwise be experienced by the patient as a side effect of the glucocorticoid component of the compositions. The therapeutic interaction of the two components therefore allows the potent antiinflammatory properties of the glucocorticoids to be utilized without fear of elevating intraocular pressure. A method of preventing increases in intraocular pressure attributable to systemic or topical corticosteroid therapy is also disclosed. That method involves the administration of a pharmaceutical composition containing tetrahydrocortisol to a patient receiving such therapy. Excerpt(s): The present invention relates to the field of ophthalmology. More particularly, this invention relates to the treatment of inflamed ocular tissue. Many compounds classified as glucocorticoids, such as dexamethasone and prednisolone, are very effective in the treatment of inflamed tissues, but in certain patients, these compounds cause elevations in intraocular pressure. Patients who experience elevations in intraocular pressure when treated with glucocorticoids are generally referred to as "steroid responders". The elevations in intraocular pressure are of particular concern in patients who are already suffering from elevated intraocular pressures, such as glaucoma patients. Moreover, there is always a risk that the use of glucocorticoids in patients who have normal intraocular pressures will cause elevations in pressure that result in damage to ocular tissue. Since therapy with glucocorticoids is frequently long term (i.e., several days or more), there is potential for significant damage to ocular tissue as a result of prolonged elevations in intraocular pressure attributable to that therapy. The following articles may be referred to for further background information concerning the well recognized association between ophthalmic glucocorticoid therapy and elevations in intraocular pressure: Kitazawa, "Increased Intraocular Pressure Induced by Corticosteroids", American Journal of Ophthalmology, Vol. 82, pages 492-495 (1976); Cantrill et al., "Comparison of In Vitro Potentcy of Corticosteroids with Ability to Raise Intraocular Pressure", American Journal of Ophthalmology, Vol. 79, pages 1012-1016 (1975); and Mindel et al., "Comparative Ocular Pressure Elevation by Medrysone, Fluorometholone, and Dexamethasone Phosphate", Archives of Ophthalmology, Vol. 98, pages 1577-1578 (1980). Web site: http://www.delphion.com/details?pn=US05358943__
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Wound diagnosis by quantitating cortisol in wound fluids Inventor(s): Hutchinson; Tyrone D. (Irving, TX), Swaniker; Hansen P. (Arlington, TX) Assignee(s): Johnson & Johnson Medical, Inc. (Arlington, TX) Patent Number: 5,912,114 Date filed: September 12, 1997 Abstract: The present invention is directed to the diagnosis and assessment of wound status by quantitating levels of cortisol present in wound fluid. The present invention is also directed to a kit and test strip for assessing wound status. Excerpt(s): Glucocorticoids are produced and secreted by the adrenal cortex. Glucocorticoids play a key role in metabolism and immune response and are typically involved in inflammation suppression. Cortisol is a glucocorticoid found in human plasma. Approximately 95% of the body's endogenous glucocorticoid supply is cortisol. Increased amounts of cortisol are released into the blood stream when the body is subjected to physiologic stresses such as illness or trauma. The release of cortisol is regulated by a physiologic cascade which starts at the hypothalamus. The hypothalamus produces corticotropin-releasing factor (CRF). CRF stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). The adrenal glands are then stimulated by ACTH to secrete additional cortisol. Once the stressor-induced physiologic demands are met, the anterior pituitary is then stimulated to decrease production and release ACTH (Howser, R. L. (1995) "Corticosteroid Therapy" American Journal of Nursing: 4449). Plasma cortisol levels typically vary between about 0.005 and 0.020 ng/ml normally. Web site: http://www.delphion.com/details?pn=US05912114__
Patent Applications on Corticosteroids 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 corticosteroids: •
Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulati- ng hormone Inventor(s): Catania, Anna Pia; (Milano, IT), Lipton, James M.; (Woodland Hills, CA) Correspondence: Lyon & Lyon Llp; Suite 4700; 633 West Fifth Street; Los Angeles; CA; 90071; US Patent Application Number: 20020137685 Date filed: September 21, 2001 Abstract: The presence of the ancient anti-inflammatory peptide.alpha.-melanocyte stimulating hormone (.alpha.-MSH [1-13], SYSMEHFRWGKPV) in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense system.alpha.MSH and other amino acid sequences derived from.alpha.-MSH were determined to have antimicrobial influences, including against two major and representative
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This has been a common practice outside the United States prior to December 2000.
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cutaneous and mucosal pathogens: Staphylococcus aureus and Candida albicans.alpha.MSH peptides had antimicrobial effects against S. aureus and significantly reversed the enhancing effect of urokinase on S. aureus colony formation.alpha.-MSH and other amino acid sequences reduced C. albicans viability and germination.alpha.-MSH peptides also enhanced C. albicans killing by human neutrophils. The antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence KPV, one or more peptides including the amino acid sequence MEHFRWG, or a biologically functional equivalent of any of the foregoing. The most effective of the peptides were those bearing the C-terminal amino acid sequence of.alpha.-MSH, i.e.,.alpha.-MSH (1-13), (6-13), and (11-13). The.alpha.-MSH "core" sequence (4-10), important for melanotropic effects, was also effective but significantly less potent. Antimicrobial influences of.alpha.-MSH peptides could be mediated by their well-known capacity to increase cellular cAMP; this messenger was significantly augmented in peptide-treated yeast.alpha.-MSH has potent anti-inflammatory effects and is expected to be useful for treatment of inflammation in human and veterinary disorders. Reduced killing of pathogens is a detrimental consequence of therapy with corticosteroids and nonsteroidal anti-inflammatory drugs during infection. Therefore, anti-inflammatory agents based on.alpha.-MSH peptides that do not reduce microbial killing, but rather enhance it, would be very useful. The antimicrobial effects of these.alpha.-MSH peptides occurred over a broad range of concentrations including the physiological (picomolar) range. Excerpt(s): The present invention relates to new pharmaceutical compositions useful as antimicrobial agents, including, for example, for use in reducing the viability of microbes, reducing the germination of yeasts, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation in which there is microbial infection without reducing microbial killing, and for increasing the accumulation of cAMP in microbes. More particularly, this invention relates to antimicrobial agents including amino acid sequences derived from alpha-melanocytestimulating hormone (.alpha.-MSH) and biologically functional equivalents thereof. Mucosal secretions, phagocytes, and other components of the nonspecific (innate) host defense system initiate the response to microbial penetration before time-consuming adaptive immunity starts. Survival of plants and invertebrates, which lack adaptive immunity, illustrates effectiveness of host defense based on such innate mechanisms. Endogenous antimicrobial peptides are significant in epithelia, the barrier to environmental challenge that provides the first line of defense against pathogens. Production of natural antimicrobial peptides by phagocytes has been recognized for a long time. These natural antimicrobial peptides generally have a broad spectrum of activity against bacteria, fungi, and viruses. Martin, E., Ganz, T., Lehrer, R. I., Defensins and Other Endogenous Peptide Antibiotics of Vertebrates, J. Leukoc. Biol. 58, 128-136 (1995); Ganz, T., Weiss, J., Antimicrobial Peptides of Phagocytes and Epithelia, Sem. Hematol. 34, 343-354 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for enhancing corticosteroid delivery Inventor(s): Gans, Eugene H.; (Westport, CT), Wortzman, Mitchell S.; (Scottsdale, AZ) Correspondence: William J. Mcnichol, JR., Esquire; Reed Smith Llp; 2500 One Liberty Place; 1650 Market Street; Philadelphia; PA; 19103-7301; US Patent Application Number: 20030130247 Date filed: December 21, 2001 Abstract: The present invention comprises a composition, method of enhancing potency and method of delivering corticosteroids in a vehicle comprising at least two penetration enhancers, and solvents and emulsifiers. The propylene glycol and penetration enhancers are present in ratio to the total of the propylene glycol, penetration enhancers, and solvents and emulsifiers of at least about 0.70. Excerpt(s): Topical corticosteroids are useful for their anti-inflammatory, anti-pruritic and vasoconstrictive actions. Corticosteroids (or corticoids) are any steroids (lipids that contain a hydrogenated cyclopentoperhydrophenanthrene ring system) elaborated by the adrenal cortex (except sex hormones of adrenal origin) in response to the release of adrenocorticotrophin or adrenocorticotropic hormone by the pituitary gland, or to any synthetic equivalent, or to angiotensin II. Corticosteroids include but are not limited to alclometasone dipropionate, amcinonide, amcinafel, amcinafide, beclamethasone, betamethasone, betamethasone dipropionate, betamethasone valerate, clobetasone propionate, chloroprednisone, clocortelone, cortisol, cortisone, cortodoxone, difluorosone diacetate, descinolone, desonide, defluprednate, dihydroxycortisone, desoximetasone, dexamethasone, deflazacort, diflorasone diacetate, dichlorisone, esters of betamethasone, flucetonide, flucloronide, fluorocortisone, flumethasone, flunisolide, fluocinonide, fluocinolone acetonide, flucortolone, fluperolone, fluprednisolone, fluroandrenolone acetonide, fluocinolone acetonide, flurandrenolide, fluorametholone, fluticasone propionate, hydrocortisone, hydrocortisone butyrate, hydrocortisone valerate, hydrocortamate, medrysone, meprednisone, methylprednisone, methylprednisolone, mometasone furoate, paramethasone, prednisone, prednisolone, prednidone, triamcinolone acetonide, and triamcinolone. Hydrocortisone was the first corticosteroid found to be topically effective. Other more potent glucocorticoids, which are a subset of corticosteroids that affect carbohydrate metabolism, inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity, have since been developed. Currently, topical steroids are among the most frequently prescribed of all dermatological drug products. It is believed that glucocorticoids exert their potent antiinflammatory effects by inhibiting the formation of prostaglandins and other derivatives of the arachidonic acid pathway. It is known that glucocorticoids inhibit the release of phospholipase A2, the enzyme responsible for liberating arachidonic acid from cell membranes, thus inhibiting the arachidonic acid pathway. Currently, it is believed that glucocorticoids inhibit phospholipase A2, in cells by directly inducing phosphorylation of the enzyme. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions for delivery of a cortisol antagonist Inventor(s): Landh, Tomas; (Lund, SE), Marin, Per; (Vastra Frolunda, SE), Ostholm, Ivan; (Goteborg, SE) Correspondence: Baker Botts L.L.P.; 44th Floor; 30 Rockefeller Plaza; New York; NY; 10112-4498; US Patent Application Number: 20020055512 Date filed: March 16, 2001 Abstract: The present invention relates to compositions for controlled release of a cortisol antagonist comprising at least one release rate controlling substance together with said cortisol antagonist and methods of preventing or treating metabolic syndrome, diabetes mellitis type II or symptoms or complications thereof in a mammal, which method comprises administering such a composition to said mammal in an amount effective to treat one or more of the clinical manifestations of metabolic syndrome or diabetes mellitis type II as well as complications thereof. Excerpt(s): The present invention relates to compositions and formulations which contain one or more cortisol antagonist, such as a cortisol synthesis inhibitor, methods for preparing such formulations and their use in therapy. More particularly, the invention relates to the use of such compositions in the prevention or treatment of metabolic syndrome and non-insulin-dependent diabetes mellitus (NIDDM), referred to herein as diabetes mellitus type II. Often a person with abnormal glucose tolerance, insulin resistance or diabetes mellitus type II will also have one or more risk factor for cardiovascular disease, stroke or other arteriosclerotic disease such as obesity, especially abdominal obesity, hypertension, dyslipidemia and microalbuminuria. This clustering has been labelled variously as metabolic syndrome, Syndrome X or Insulin Resistance Syndrome. An attempt to more adequately describe metabolic syndrome was recently done (Diabet. Med. 1998, 15, 539-553) and a working definition for the clinical recognition of the condition was suggested to include the following characteristics: glucose intolerance, abnormal glucose tolerance or diabetes mellitus and/or insulin resistance together with two or more of the components: (1) Impaired glucose regulation or diabetes (2) Insulin resistance (3) Raised arterial blood pressure (4) Raised plasma triglycerides and/or low HDL-cholesterol (5) Central obesity and/or a body mass index of more than 30 kg/m.sup.2 (6) Microalbuminuria. Those patients with metabolic syndrome are at very high risk of developing diabetes and therefore vigorous early management of metabolic syndrome may have a significant impact on the prevention of diabetes. All of the physiological imbalances associated with metabolic syndrome are risk factors for cardiovascular disease and thus effective early management of metabolic syndrome may also have a significant impact on the prevention of cardiovascular disease, stroke and other arteriosclerotic diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compound and method for the treatment of sinusitis Inventor(s): Catania, Anna P.; (Milan, IT), Lipton, James M.; (Woodland Hills, CA) Correspondence: Perkins Coie Llp; Post Office Box 1208; Seattle; WA; 98111-1208; US Patent Application Number: 20030109453 Date filed: December 10, 2001
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Abstract: The invention includes a composition and method of treatment of sinusitis. A preferred embodiment of the invention is a composition for treatment of sinusitis comprising a therapeutically effective amount of one or more peptides selected from the group of peptides with a C-terminal sequence consisting of KPV, HFRWGKPV, and SYSMEHFRWGKPV used in combination with a therapeutically effective amount of an antihistamine/decongestant, corticosteroid, fungicide and/or antibiotic.In yet another embodiment of the invention, one or one or more peptides selected from the group of peptides with a C-terminal sequence consisting of KPV, HFRWGKPV, and SYSMEHFRWGKPV, which may or may not be in combination with therapeutically effective amounts of antibiotics, corticosteroids and/or antihistamine/decongestants, are topically or systemically applied to treat sinusitis. Excerpt(s): This invention relates to the field of pathologies of the mucosal membranes of the head and facial sinus cavities caused by inflammation. The sinuses are air pockets located inside the bones in the skull. They are located to either side of the nose (maxillary), behind and in between the eyes (ethmoid), in the forehead (frontal), and there is one much further back in the head (sphenoid). Each sinus is drained by a small hole, about 4 mm in diameter, called an ostium. The sinuses are lined with very fine hair-like projections called cilia. The function of the cilia is to encourage the drainage of mucus. Sinusitis is frequently caused by an obstructed ostium. This obstruction may result from an anatomical defect such as a deviated septum, inflammation due to an upper respiratory infection or an allergic response, drying of the mucus, or a foreign body caused from an accident. When this occurs, mucus that normally is expelled from the sinus builds up in the sinus causing pain, pressure and an excellent culture medium for bacteria. If the mucus is not cleared immediately, an abscess can develop in the sinus. Unfortunately, draining the abscess is not feasible without doing extensive surgery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Computerized identification of normal and abnormal diurnal cortisol secretion patterns and levels of testosterone from human saliva samples Inventor(s): Martin, Lene; (Stockholm, SE), Wagner, Peter; (Stockholm, SE) Correspondence: Steven S. Payne; 8027 Iliff Drive; Dunn Loring; VA; 22027; US Patent Application Number: 20040039719 Date filed: May 30, 2003 Abstract: Normal and abnormal diurnal cortisol secretion patterns are identified from human saliva samples by an in vitro method. First and second saliva samples are taken from one human individual at first and second predetermined times during the same day. A first cortisol concentration is determined in the first saliva sample, and a second cortisol concentration is determined in the second saliva sample. An abnormal secretion pattern is then compared to a normal secretion pattern with the help of a fuzzy logic algorithm. A function of the hypothalamic-pituitary-adrenal (HPA) axis is then determined for the human individual. Optionally, a testosterone level is determined from one of the samples and is used in combination with the cortisol concentrations to provide a redefined determination. Excerpt(s): The present invention relates to identification of normal and abnormal diurnal cortisol secretion patterns and levels of testosterone from human saliva samples, so as to determine the function of the hypothalamic-pituitary-adrenal (HPA) axis in
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individual subjects. The joint operation of the above functions, in the medical literature commonly referred to as the hypothalamic-pituitary-adrenal (HPA) axis, constitutes an important mechanism for maintaining steady state in the human organism. Disturbances in this mechanism have been shown to lead to metabolic complications, such as increased insulin resistance and abdominal obesity. These metabolic abnormalities are associated with increased risk for cardiovascular disease, the major cause of death in industrialized countries. A review of the above is found in "Neuroendocrine perturbations as a cause of insulin resistance" in Diabetes/Metabolism Research and Reviews 1999; 15:427-441, by Bjorntorp P. For a more detailed description see "Psychoneuroendocrine aspects on the metabolic syndrome", ISBN 91-628-3195-X, by Rosmond R., Goteborg University 1993. Abnormal concentrations of cortisol have also been shown to be the biochemical mechanism for the influence of external stress factors on the metabolic system, which lead to increased risk for heart disease, in both humans and experimental animals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
CORTICOID-17,21-DICARBOXYLIC ESTERS AND CORTICOSTEROID 17CARBOXYLIC ESTER 21-CARBONIC ESTERS, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICALS CONTAINING THESE COMPOUNDS Inventor(s): ALPERMANN, HANS-GEORG; (KONIGSTEIN, DE), BOHN, MANFRED; (HOFHEIM, DE), DURCKHEIMER, WALTER; (HATTERSHEIM, DE), STACHE, ULRICH; (HOFHEIM, DE) Correspondence: Finnegan Henderson Farabow; Garrett And Dunner; 1300 I Street NW; Washington; DC; 200053315 Patent Application Number: 20020103392 Date filed: July 22, 1997 Abstract: Corticoid 17,21-dicarboxylic esters and corticosteroid 17-carboxylic ester 21carbonic esters, processes for their preparation and pharmaceuticals containing these compoundsCorticoid 17,21-dicarboxylic esters and corticoid 17-carboxylic ester 21carbonic esters of the formula I 1are described, in which A is CHOH and CHCl, CH.sub.2, C.dbd.O or 9(11) double bond; Y is H, F or Cl; Z is H, F or methyl; R(1) is aryl or hetaryl; R(2) is alkyl and R(3) is H or methyl. They are obtained, inter alia, by reacting a compound of the formula II, 2in which R(5) is OH, with an activated carboxylic acid of the formula III,R(6)--CO--(O).sub.n[(C.sub.1-C.sub.4)-alkyl].sub.m-R(1) III.They have a very strong local and topical antiinflammatory action and exhibit a very good ratio of local to systemic antiinflammatory effects. They are used, inter alia, as agents for treating inflammatory dermatoses. Excerpt(s): R(3) is hydrogen or.alpha.- or.beta.-methyl. Me preferably being the cation of an alkali metal salt or of a trialkylammonium salt. The steroid 17-carboxylic esters with a free 21-hydroxyl group of the formula II [R(5).dbd.OH], which are required as starting substances, are as a rule known or are prepared by known methods. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cortisol sensor Inventor(s): Lawrence, David S.; (Olney, MD), Sample, Jennifer L.; (Bethesda, MD) Correspondence: Francis A. Cooch, Office OF Patent Counsel; The Johns Hopkins University; Applied Physics Laboratory; 11100 Johns Hopkins Road; Laurel; MD; 207236099; US Patent Application Number: 20030224526 Date filed: May 20, 2003 Abstract: Devices and methods for sensing and detecting cortisol levels in a fluid sample in real-time using a cortisol-imprinted polymer are provided. Also provided are hydration devices comprising a cortisol sensor of the present invention capable both of providing hydration to a user and allowing the user to measure cortisol levels in the user's bodily fluids in real-time. Excerpt(s): The present application claims the benefit of prior filed Provisional Application No. 60/383,543 which was filed with the United States Patent and Trademark Office on May 28, 2002. The entire disclosure of the above-referenced application is incorporated herein by reference. The present invention relates generally to sensor devices comprising molecularly imprinted polymers for use in real-time detection of cortisol levels in a fluid sample, and methods for using such devices to detect cortisol levels in real time. Methods and apparatus for the efficient and accurate detection and quantification of cortisol (or hydrocortisone) levels are of particular interest for use in a wide range of applications. For example, because cortisol (a steroid produced in the human body by the adrenal gland) is known to be a regulator of many biological functions, has been identified as a biomarker for many diseases (e.g. Cushing's Syndrome), and has been correlated with levels of stress, the measurement of cortisol in the human body is an important tool for use in clinical diagnostics and in monitoring stress levels during stress-intensive activities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Determination of corticosteroids in human plasma using micromass LC/MS/MS/ Inventor(s): Gao, Feng; (Stamford, CT) Correspondence: Pennie & Edmonds Llp; 1667 K Street NW; Suite 1000; Washington; DC; 20006 Patent Application Number: 20020168775 Date filed: February 21, 2001 Abstract: The present invention is directed to a method of detecting a corticosteroid in a sample by adding an internal standard to a sample suspected of containing a corticosteroid; removing interfering compounds from the sample; placing the sample on an HPLC column equilibrated with a NH.sub.4OAc:MeOH solution and collecting an eluent; and analyzing the eluent of the HPLC column with a MS, wherein if contained in the sample, the corticosteroid forms an adduct that is detected by the MS. Excerpt(s): The invention is directed to methods for quantitatively determining the presence and/or amount of a corticosteroid in a solution by forming a corticosteroidacetate adduct and detecting the adduct using a micromass LC/MS/MS system. These methods accurately detect trace amounts of corticosteroids. Optionally, these methods further detect other drug agents present in concentrations much greater than the
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corticosteroids to be detected. Preferably, the methods are used to substantially simultaneously detect and determine the amount of dexamethasone and other compounds such as bupivacaine within human plasma. The quick and accurate determination of drugs within human plasma is of paramount importance in many medical applications. Methods that accurately and quickly determine even trace amounts of a drug in the bloodstream are particularly useful. Moreover, these detection methods become of particular importance in the use of high potency drugs because unwanted side effects are produced when safe dosage levels are exceeded. Potent drugs can include, for example, glucocorticoids which can exacerbate neuronal damage due to hypoxia, ischemia, seizure, and hypoglycemia. Consequently, research has focused on developing drug detection and/or quantification methods that concurrently analyze samples such as plasma for a variety of compounds in differing amounts. This research, however, has been hampered because detection readings can be misinterpreted when the drugs to be detected are structurally similar to other compounds within the sample and/or the drugs are present in minute concentrations within the sample. The effects of corticosteroids are numerous and widespread. Their diverse effects include: alterations in carbohydrate, protein, and lipid metabolism; maintenance of fluid and electrolyte balance; and preservation of normal function of the cardiovascular system, the immune system, the kidney, skeletal muscle, the endocrine system, and the nervous system. In addition, by mechanisms that are still not fully understood, corticosteroids provide the organism with the capacity to combat stressful circumstances such as noxious stimuli and environmental changes. For example, in the absence of the adrenal cortex, survival is made possible only by maintaining an optimal environment, including adequate and regular feedings, ingestion of relatively large amounts of sodium chloride, and maintenance of an appropriate environmental temperature. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for the preparation of 6alpha-fluoro corticosteroids Inventor(s): Chernyak, Shimon; (Yokneam Yllit, IL), Gutman, Daniella; (Rishon LeZion, IL), Zarbov, Martin; (Kiriat Haim, IL) Correspondence: Venable, Baetjer, Howard And Civiletti, Llp; P.O. Box 34385; Washington; DC; 20043-9998; US Patent Application Number: 20030162959 Date filed: November 27, 2002 Abstract: A method for producing a 6.alpha.-fluorinated corticosteroid or derivative thereof by reacting a 17-hydroxy-21-ester epoxide of Formula II 1with a stereoselective fluorinating agent to stereoselectively form a 21-ester-17-hydroxy 6.alpha.-fluorinated compound of Formula VII 2R.sup.1 can be OC(O)--R.sub.d; R.sup.4 can be C(O)-R.sub.d; R.sup.3 can be H or R.sub.d. Each R.sub.d may be the same or different and is independently selected from (C.sub.1-4)alkyl, aryl and heteroaryl. The dashed line can be a single or a double bond. R.sup.4 may be, for example, acetyl; R.sup.3 may be, for example, alpha or beta methyl; R.sup.4 may be, for example, acetate or propionate. The stereoselective fluorinating agent used in the reaction may be, for example, a fluoropyridinium or fluoroquinuclidium compound, for example, Selectfluor.RTM. Excerpt(s): The present invention relates to the manufacture of 6.alpha.-fluorinated corticosteroids. In particular, the invention relates to the manufacture of 6.alpha.,9.alpha.-difluoro-11.beta.,17.alph- a.,21-trihydroxy-16.alpha.(or.beta.)-methylprednisolones and their 17- and/or 21-substituted derivatives. Examples of compounds
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in this class include diflorasone (R.sup.1=OH, R.sup.3=.beta.-methyl), flumethasone (R.sup.1=OH, R.sup.3=.alpha.-methyl), and halobetasol propionate. These agents have a 6-fluoro substituent exclusively in the alpha-(equatorial) configuration. Derivatives of these compounds, e.g., diflorasone diacetate, halobetasol propionate, flumethasone acetate etc., have also been shown to have enhanced anti-inflammatory activity. Traditional methods for inserting fluorine in the 6-position of the steroid molecule consist of converting the corresponding 3-ketosteroids into appropriate 3-enolates and reacting these unstable intermediates with a source of electrophilic fluorine. Common sources of electrophilic fluorine that have been used are frequently toxic and gaseous, for example perfluoryl perchlorate. These known procedures generally lead to mixtures of both the 6-.alpha.- and 6-.beta.-diastereomers which must then be separated by, for example, crystallization or column chromatography. For pregn-4-enes, the relative amount of alpha-epimer may be increased by bubbling anhydrous hydrogen chloride through a mixture of isomers in an inert organic solvent (See, for example, U.S. Pat. No. 4,036,831). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
METHOD FOR TREATING AND/OR PREVENTING RETINAL DISEASES WITH SUSTAINED RELEASE CORTICOSTEROIDS Inventor(s): Ashton, Paul; (Boston, MA), Guo, Hong; (Belmont, MA) Correspondence: Mcdermott, Will & Emery; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20020127250 Date filed: December 14, 2000 Abstract: The present invention relates to a method for administering a corticosteroid to a posterior segment of an eye. In the method, a sustained release device is implanted to deliver the corticosteroid to the eye. The aqueous corticosteroid concentration remains less than vitreous corticosteroid concentration during release of the corticosteroid from the device. Excerpt(s): The present invention relates to the field of controlled pharmaceutical delivery, particularly to corticosteroids. Compounds classified as corticosteroids, such as triamcinolone, can effectively treat some forms of neovascularization such as corneal neovasularization. In general, corticosteroids have been unsuccessful in treating neovscularization of the posterior segment. In many patients, these compounds cause undesirable side effects. These adverse affects include elevations in intraocular pressure and the formation of, or acceleration of, the development of cataracts. Elevations in intraocular pressure are of particular concern in patients who are already suffering from elevated intraocular pressure, such as glaucoma patients. Moreover, a risk exists that the use of corticosteroids in patients with normal intraocular pressure will cause elevations in pressure that result in damage to ocular tissue. Since therapy with corticosteroids is frequently long term, i.e., several days or more, a potential exists for significant damage to ocular tissue as a result of prolonged elevations in intraocular pressure attributable to that therapy. One approach to solving the foregoing problems has been to search for specific compounds which are effective in treating neovascularization without elevating intraocular pressure. Another approach has been to administer corticosteroids in conjunction with another drug to "block" or reduce the IOP elevating effects of the corticosteroids or to treat IOP elevation separately with another drug. A further
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approach has been neovascularization.
to
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of making 21-[4'-(nitrooxyalkyl)benzoate] corticosteroid derivatives and intermediates useful in the synthesis thereof Inventor(s): McIntyre, Donald G.; (Raleigh, NC) Correspondence: Allen R. Baum; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030153545 Date filed: May 21, 2002 Abstract: The present invention provides methods of making 21-[4'-(nitrooxyalkyl)benzoate] corticosteroid derivatives according to the following general reaction scheme: 1The invention also provides intermediates useful in making such 21-[4'(nitrooxyalkyl)benzoate] corticosteroid derivatives as well as methods for making such intermediates. Excerpt(s): This application claims the priority benefit of U.S. Provisional Application No. 60/292,792 filed May 22, 2001, the entire disclosure of which is incorporated herein by reference. The present invention relates to methods for making 21-[4'(nitrooxyalkyl)benzoate] corticosteroid derivatives and also relates to intermediates useful in making such compounds. Corticosteroids are known to have antiinflammatory and immunomodulatory properties useful in the treatment of numerous diseases, including autoimmune and inflammatory diseases. However, treatment with corticosteroids may cause undesirable side-effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmaceutical composition for treatment of phimosis using topical corticosteroid Inventor(s): Palma, Paulo Cesar Rodrigues; (Svo Paulo, BR) Correspondence: Wood, Herron & Evans, Llp; 2700 Carew Tower; 441 Vine Street; Cincinnati; OH; 45202; US Patent Application Number: 20040067922 Date filed: October 31, 2003 Abstract: This invention addresses the pharmaceutical composition for topical corticosteroid use in association with diffusing enzyme for treatment of phimosis. A pharmaceutical composition for treatment of phimosis using topical corticosteroid characterized by including around 0.025 to 5 percent in weight in relation to the total weight of the mixture composition of one or more corticosteroids and/or hormone steroids, whether or not associated with non-hormonal anti-inflammatory agents and around 25 UTR to 4000 UTR/g of one or more proteolytic diffusing enzymes in proper medium, in different pharmaceutical forms, accompanied with additives known to the technical man. Topical corticosteroid application in association with diffusing enzyme for treatment of phimosis in which 90 percent of the patients had improvements over their clinical complaints, with the prepuce being easily retracted.
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Excerpt(s): This invention addresses the use of pharmaceutical composition for topical corticosteroid and/or hormonal steroids in association with proteolytic diffusing enzyme, whether or not in the presence of non-hormonal anti-inflammatory agents, for treatment of phimosis. The invention scope includes the pharmaceutical industry, prescription compounding services, and physicians. Phimosis is more often suspected than actually found. What most frequently happens is an adhesion of the prepuce and the glans, which will detach normally from each other over time. Typically, the prepuce will not retract at birth, but this condition is often resolved within the initial four years of age. As the penis gets larger, epithelial debris will build up under the prepuce and eventually separate the prepuce from the glans. In countries where circumcision is not performed commonly, treatment is seldom found to be necessary. Spontaneous improvement comes with maturity. The incidence of phimosis decreases from 8 percent to 1 percent in adolescents (Oster J, Further Fate of the Foreskin, Arch Dis Child, 1968, 43: 200-3). The number of cases is as low as 0.4/1000 boys per year. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical compositions based on anticholinergics and corticosteroids Inventor(s): Meade, Christopher John Montague; (Bingen, DE), Pairet, Michel; (Biberach, DE), Pieper, Michael P.; (Bingen, DE), Reichl, Richard; (Gau-Algesheim, DE), Schmelzer, Christel; (Ingelheim, DE) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20020183292 Date filed: October 19, 2001 Abstract: A pharmaceutical composition comprising an anticholinergic and a steroid, optionally together with a pharmaceutically acceptable excipient, the anticholinergic and the steroid optionally in the form of their enantiomers, mixtures of their enantiomers, their racemates, their solvates, or their hydrates, processes for preparing them, and their use in the treatment of respiratory tract diseases. Excerpt(s): Benefit under 35 U.S.C.sctn. 119(e) of prior provisional application Serial No. 60/253,613, filed Nov. 28, 2000, and prior provisional application Serial No. 60/257,220, filed Dec. 21, 2000, is hereby claimed. The present invention relates to novel pharmaceutical compositions based on anticholinergics and corticosteroids, processes for preparing them and their use in the treatment of respiratory diseases. Surprisingly, it has been found that an unexpectedly beneficial therapeutic effect, particularly a synergistic effect can be observed in the treatment of inflammatory or obstructive diseases of the respiratory tract if one or more anticholinergics are used with one or more corticosteroids. In view of this synergistic effect the pharmaceutical combinations according to the invention can be used in smaller doses than would be the case with the individual compounds used in monotherapy in the usual way. This reduces unwanted side effects such as may occur when corticosteroids are administered, for example. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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•
Pharmaceutical betamimetics
compositions
based
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Inventor(s): Meade, Christopher J.M.; (Bingen, DE), Pairet, Michel; (Biberach, DE), Pieper, Michael P.; (Bingen, DE) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20030018019 Date filed: June 17, 2002 Excerpt(s): The present invention relates to novel pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics, processes for preparing them and their use in the treatment of respiratory diseases. The present invention relates to novel pharmaceutical compositions based on anticholinergics, corticosteroids and betamimetics, processes for preparing them and their use in the treatment of respiratory diseases. Surprisingly, an unexpectedly beneficial therapeutic effect, particularly a synergistic effect can be observed in the treatment of inflammatory or obstructive diseases of the respiratory tract if one or more, preferably one, anticholinergic is used with one or more corticosteroids and with one or more betamimetics. In view of this synergistic effect the pharmaceutical combinations according to the invention can be used in smaller doses than would be the case with the individual compounds used in monotherapy in the usual way. Furthermore, this reduces unwanted side effects such as may occur when corticosteroids and betamimetics are administered, for example. The effects mentioned above may be observed both when the three active substances are administered simultaneously in a single active substance formulation and when they are administered successively in separate formulations. According to the invention, it is preferable to administer the active substance ingredients simultaneously in a single formulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Topical solution formulations containing an antibiotic and a corticosteroid Inventor(s): Bhagat, Haresh G.; (Fort Worth, TX), Singh, Onkar N.; (Arlington, TX) Correspondence: Alcon Universal LTD.; C/o Alcon Research, LTD.; R&d Counsel (q148); 6201 South Freeway; Forth Worth; TX; 76134-2099; US Patent Application Number: 20010049366 Date filed: February 8, 2001 Abstract: Solution formulations containing a corticosteroid, an antibiotic and a vitamin E tocopheryl derivative as a solubilizing agent are disclosed. The formulations are intended for topical application to the eye, ear, nose or skin. Excerpt(s): This application claims priority to now abandoned U.S. Provisional Application, Ser. No. 60/181,317, filed February 9, 2000. This invention relates to topically administrable solution formulations containing an antibiotic, a corticosteroid and a solubilizing agent. Both solution and suspension compositions containing dexamethasone as the sole active agent are marketed. The solution compositions contain dexamethasone in the form of dexamethasone sodium phosphate. The suspension formulations contain dexamethasone in the form of dexamethasone alcohol. See Ophthalmic Drug Facts '99, Facts and Comparisons, St. Louis, Mo. (1999), p. 87.
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Additionally, aqueous anti-inflammatory/anti-infective combination products containing dexamethasone are currently marketed. See Ophthalmic Drug Facts '99, Facts and Comparisons, St. Louis, Mo. (1999), p. 121-122. The only such combination product identified as a solution is a neomycin sulfate/dexamethasone sodium phosphate solution product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treating asthma by preventing and/or accomodating for S-nitrosothiol breakdown Inventor(s): Gaston, Benjamin; (Charlottesville, VA), Griffith, Owen W.; (Milwaukee, WI), Stamler, Jonathan S.; (Chapel Hill, NC) Correspondence: Eric S. Spector; Jones, Tullar & Cooper, P.C.; Eads Station; P.O. Box 2266; Arlington; VA; 22202; US Patent Application Number: 20030170316 Date filed: April 1, 2003 Abstract: Asthma is ameliorated, and mild or moderate asthma is prevented from progressing to more severe asthma by administering agents which prevent and/or accommodate for S-nitrosothiol breakdown. The method reduces requirements for systemic corticosteroids for the treatment of severe asthma. Excerpt(s): This invention is directed to treating a patient with asthma to ameliorate the symptoms thereof, to treating patients with mild or moderate asthma to inhibit progression to more severe asthma, and to reducing corticosteroid requirements in patients with severe asthma. About 10 million asthmatics live in the USA. Asthma sufferers are subject to acute attacks characterized by increased responsiveness of the tracheobronchial tree to various stimuli, which leads to generalized airway constriction manifested by dyspnea, cough and wheezing. Asthma sufferers often experience acute exacerbations of bronchoconstriction, which may be life-threatening. The degrees of severity of an acute asthma attack have been classified as mild, moderate and severe in NIH Publication No. 97-4051 (April 1997) of the National Heart, Lung and Blood Institute of the National Institutes of Health and these classifications are used herein and NIH Publication No. 97-4051 is incorporated herein by reference. A patient presenting with severe asthma is treated with a series of drugs including inhaled beta.sub.2-agonist and anticholinergic and systemic corticosteroid medications, and is given oxygen to achieve O.sub.2 saturation.gtoreq.90%. Any patient with impending or actual respiratory failure is treated with parenteral beta.sub.2-agonist, inhaled anticholinergic and parenteral corticosteroid medications, and if no favorable response is shown, by endotracheal intubation and mechanical ventilation and treatment in an intensive care unit. Annually several thousand patients with severe asthma die. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of agonists of the glucocorticosteroid and/or mineralo-corticosteroid receptors, in particular corticosteroids for the treatment of addiction Inventor(s): Wolffgramm, Jochen; (Berlin, DE) Correspondence: Fish & Neave; 1251 Avenue OF The Americas; 50th Floor; New York; NY; 10020-1105; US Patent Application Number: 20020045608 Date filed: May 9, 2001 Abstract: Use of agonists of corticosteroid receptors and/or mineralo-corticoid receptors and an addictive drug or the pharmacodynamic equivalent thereof in the production of a medicament for the therapy of an addictive disease triggered by said addictive drug or connected thereto. Excerpt(s): The present invention relates to the use of agonists of the glucocorticosteroid and/or mineralo-corticosteroid receptors, in particular corticosteroids, for the treatment of addictive diseases, a pharmaceutical preparation for the treatment of addictions and a method for the treatment of addictions. Alcohol and drug addiction have been considered non-curable up to now. All therapy programs, even the new approaches of an "anti-craving" pharmacotherapy, could only support the addicted patient in his will not to have a relapse after withdrawal but they cannot reverse the core of the disease-the latent loss of control over taking of drugs. This is why the risk of a relapse is still high many years after withdrawal. Alcohol and drug addiction (often called "dependency") is a psychological disease with a compulsively increased selfadministration of the addictive drug. The addicted consumer is not able to regulate his intake of drugs, to adjust it to his currently prevalent conditions (e.g. the present social situation) and to take alternative behaviour into consideration (American Psychiatric Association, 1994). The "loss of control" , once started, disappears only extremely slowly; even more, it seems to be spontaneously irreversible in many cases (Sobell et al., 1993). This "loss of reversibility" becomes statistically clear when looking at the extremely high percentage of relapses even afterlong periods of abstinence. In follow-up studies after detoxification and subsequent therapy of alcohol addicts, only a quarter up to a third, at the most, of the addicted patients remained abstinent permanently (SuB, 1995; Veltrup et al., 1995). Spontaneous recovery success and higher percentages of long-term abstinent patients are usually due to the fact that--due to the inclusion criteria of the relevant study--not only clearly addicted patients but also "problem drinkers", i.e. patients with excessive but still controlled alcohol consumption, were included in the study (compare Stetter and Axmann-Kremar, 1996; Wieser and Kunad, 1965). For other drugs (opiates, cocaine, amphetamine derivatives), less reliable follow-up data are available. Usually, one starts out from an even worse cure prognosis for opiate addiction than for alcohol addiction (compare Roch et al., 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of cortisol-sequestering agents for the treatment of hypercortisolaemia related disorders Inventor(s): Hill, David Robert; (Sctoland, GB), Rees, David; (Cambridge, GB), Zhang, Mingqiang; (Kirkland, CA) Correspondence: William M Blackstone; Akzo Nobel Patent Department; Intervet Inc; 405 State Street; Millsboro; DE; 19966; US Patent Application Number: 20040048830 Date filed: September 2, 2003 Abstract: The invention relates to the use of sequestering agents for the preparation of a medicament for the treatment of hypercortisolaemia related disorders, especially for the treatment of major depression; to pharmaceutical compositions comprising a cortisolsequestering agent, and to the cortisol-sequestering agent 6-per-deoxy-6-per-(2,3dihydroxypropyl- thio)-.gamma.-cyclodextrin. Excerpt(s): The invention relates to the use of sequestering agents for the preparation of a medicament for the treatment of hypercortisolaemia related disorders, especially for the treatment of major depression. One of the most consistent findings in psychiatry is that patients with major depression present with hypercortisolaemia (Holsboer, F. et al., Cortisol, 11-deoxy-cortisol and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers. Psychiatry Res. 11, 15-23, 1984)). This hypercortisolaemia can reach an order of magnitude and indicates a gross disturbance in the negative feedback mechanisms that normally strongly regulate the endocrine stress HPA (hypothalamo-pituitary-adrenal) axis. Although not all depressed patients have manifest hypercortisolaemia, patients who suffer the most severe types of monoamine-resistant depression are in majority those in whom high levels of the stress hormone cortisol are apparent. Further, in almost all cases they exhibit a clear inability to switch off endogenous cortisol release following exogenous challenge with the potent synthetic glucocorticoid dexamethasone (the so-called dexamethasone non-suppressors) (Gold P. W., et al., Clinical and biochemical manifestations of depression: relation to neurobiology of stress. New England J. Med. 319, 413-420, 1988). This `sub-group` of severely compromised patients are most often the ones in whom depression becomes a life-threatening illness that warrants hospitalisation. A prompt treatment strategy like electroconvulsive therapy (ECT) may be necessary in such patients. Another condition in which high cortisol levels are reported as a result of adrenal gland malfunction (due to a pituitary tumour or a secondary tumour, both producing the cortisol secretagogue ACTH) is the Cushing's syndrome. The depressive symptoms associated with Cushing's disappear relatively quickly once the underlying cause of the disease has been treated, with the return of cortisol levels to normal. Such treatment may involve removal of the offending tumour or treatment with cortisol synthesis inhibitors such as metyrapone, ketoconozole, or aminoglutethimide (Murpy, B. E. P., Steroids and Depression. J. Steroid Biochem & Mol. Biol. 38, 537-558, 1991). 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 corticosteroids, you can access the U.S. Patent Office archive via the Internet at the following Web address:
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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 “corticosteroids” (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 corticosteroids. You can also use this procedure to view pending patent applications concerning corticosteroids. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON CORTICOSTEROIDS Overview This chapter provides bibliographic book references relating to corticosteroids. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on corticosteroids include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “corticosteroids” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on corticosteroids: •
Oral Disease: Colour Guide. 2nd ed Source: Edinburgh, Scotland: Churchill Livingstone. 1999. 174 p. Contact: Available from W.B. Saunders Company, A Harcourt Health Sciences Company. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St Louis, MO 63146-9988. (800) 545-2522. Fax (800) 568-5136. E-mail:
[email protected]. Website: www.wbsaunders.com. PRICE: $19.95 plus shipping and handling. ISBN: 044306170X. Summary: This book is intended as an aid to oral medicine and the diagnosis and treatment of oral disease. The format describes diseases initially by site, as this is how patients present. The text and illustrations (full color photographs) cover the common conditions seen in oral medicine, and some of the less common and exotic. Photographs and descriptions are offered in 12 chapters: lip lesions, intraoral lesions (mucosal ulcers),
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intraoral white lesions, intraoral colored or pigmented lesions, intraoral lumps, tongue lesions, gingival lesions, major salivary gland disease, cervical lymph node swellings, neurological disorders, teeth disorders, and HIV disease. An appendix lists common drug therapies used for oral diseases, including dosages and contraindications for analgesics, anxiolytics, corticosteroids, systemic immunosuppressants, antifungals, antivirals, antidepressants. The handbook concludes with a subject index. •
Pneumocystis Carinii Pneumonia Contact: Marcel Dekker, Incorporated, 270 Madison Ave, New York, NY, 10016, (800) 228-1160. Summary: This book presents a comprehensive examination of all aspects of Pneumocystis carinii pneumonia (PCP). This form of pneumonia is prevalent among people with AIDS and other immunosuppressed patients. The author has included a review of recent advances in basic biology, epidemiology, pathophysiology, clinical features, diagnosis, treatment, and prevention of this opportunistic infection. The book contains a treatment section detailing important topics in drug development and includes discussions of pentamidine; folate antagonists; primaquine, other 8aminoquinolines, and clindamycin; hydroxynapthoquinones, glucan synthetase inhibitors, and corticosteroids.
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Lupus: A Patient Care Guide for Nurses and Other Health Professionals Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH). 1998. 146 p. Contact: Available from National Arthritis and Musculoskeletal and Skin Diseases Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.nih.gov/niams. PRICE: Single copy free. Summary: This handbook provides nurses and other health professionals with an overview of lupus erythematosus and caring for patients with the disease. The handbook focuses on systemic lupus erythematosus (SLE), a chronic, inflammatory, multisystem disorder of the immune system in which the body develops antibodies that react against the person's own normal tissue. Chapter 1 provides a general overview of the disease, including brief discussions of the diagnosis, treatment, medications, and psychosocial aspects. Chapter 2 reviews the current understanding of the etiology (cause) of lupus and describes areas of ongoing research. Chapter 3 summarizes the main laboratory tests used to determine whether a patient has lupus and to monitor a patient's condition. These assessments include blood tests, measurements of autoimmunity, and tests for kidney disease. Chapter 4 offers a system by system overview of the most common lupus manifestations and suggests nursing interventions for each. Several other key issues are discussed in this chapter, including general manifestations, pregnancy, infection, and nutrition. Chapter 5 covers the major categories of drugs currently used to control lupus symptoms: nonsteroidal antiinflammatory drugs, antimalarials, corticosteroids, and immunosuppressives. The authors discuss each category of medication, its mechanism of action and use in treating lupus, and the potential side effects associated with each category. In Chapter 6, which addresses the psychosocial aspects of lupus, the authors note that because of the chronic, unpredictable, and evolving nature of lupus, patients often have to cope with serious emotional and psychosocial issues along with the physical dimensions of their illness. Chapter 6 also offers numerous quotations from patients, to give health care providers a
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better sense of what patients experience when coping with lupus. Chapter 7, entitled Patient Information, contains 16 short fact sheets covering a broad range of issues related to lupus, including 5 fact sheets which deal with lupus medications. The fact sheets are designed to help patients understand their disease, its symptoms, and its complications and to help patients develop effective ways of living with and controlling lupus. The handbook closes with a chapter of resources for further information on lupus, a bibliography of the source materials used to develop the book, and a subject index. •
Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment Source: Boston, MA: Kluwer Academic Publishers. 1998. 176 p. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail:
[email protected]. Website: www.wkap.nl. Summary: This monograph reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of primary biliary cirrhosis (PBC). PBC is generally considered to be an autoimmune disease and one that occurs in patients who are genetically predisposed to the disease. The part played by mitochondrial antibodies (AMA) in pathogenesis of PBC remains controversial. Alternatively, the disease may have an infectious etiology (cause). Therapy can be directed against any of these injurious processes. Drug therapy, notably combinations of drugs, can be used. Fibrosis (scarring) of the bile ducts occurs in PBC and is responsible for the end picture of cirrhosis (liver scarring). Complications such as ascites (fluid accumulation) and portal hypertension (high blood pressure) need to be treated; other complications can include bone thinning and pruritus (itching). Liver (hepatic) transplantation performed before the terminal stages of PBC offers a five year survival exceeding 85 percent. There is evidence of recurrence in the graft. The monograph includes 20 chapters covering the natural history and demography of PBC, the immune basis for PBC, isolation and cloning of antimitochondrial antibodies, determining pathogenesis, molecular considerations of PBC, animal models of PBC, fibrogenesis in PBC, natural history models, portal hypertension in patients with PBC, osteoporosis, managing fatigue in the patients with PBC, pruritus associated with cholestasis (suppression of the flow of bile), immunosuppressant agents, methotrexate and colchicine in the treatment of PBC, corticosteroids in PBC, ursodeoxycholic acid treatment of PBC, ursodiol and combination therapy, transplantation, and new clinical trials in PBC. Each chapter concludes with references and a subject index concludes the monograph.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “corticosteroids” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “corticosteroids” (or a synonym) in their titles. The following is indicative of the results you might find when searching for
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“corticosteroids” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Brain Corticosteroid Receptors: Studies on the Mechanism, Function, and Neurotoxicity of Corticosteroid Action (Annals of the New York Academy of) by E. R. De Kloet, et al; ISBN: 0897669088; http://www.amazon.com/exec/obidos/ASIN/0897669088/icongroupinterna
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Effect of corticosteroids for fetal maturation on perinatal outcomes : January 1985 through December 1993, plus slected earlier citations : 715 citations (SuDoc HE 20.3615/2:94-1) by Karen Patrias; ISBN: B00010IFIS; http://www.amazon.com/exec/obidos/ASIN/B00010IFIS/icongroupinterna
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Effects of corticosteroids for fetal maturation on perinatal outcomes : January 1985 through December 1993, plus selected earlier citations : 715 citations (SuDoc HE 20.3615/2:94-1) by Karen Patrias; ISBN: B00010K0P4; http://www.amazon.com/exec/obidos/ASIN/B00010K0P4/icongroupinterna
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LEE PROGRESS IN RESEARCH AND CLINICAL APPLICATIONS OF CORTICOSTEROIDS (NOT HANDLED BY NY) by HJ LEE; ISBN: 0471262102; http://www.amazon.com/exec/obidos/ASIN/0471262102/icongroupinterna
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Mechanisms of topical corticosteroid activity: A Glaxo symposium; ISBN: 0443014418; http://www.amazon.com/exec/obidos/ASIN/0443014418/icongroupinterna
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Principles of Corticosteroid Therapy by Andrew N. Lin, Stephen A. Paget; ISBN: 0340759348; http://www.amazon.com/exec/obidos/ASIN/0340759348/icongroupinterna
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Role of corticosteroids in bone loss during space flight final report (SuDoc NAS 1.26:208220) by Thomas Joseph Wrongski; ISBN: B0001106WU; http://www.amazon.com/exec/obidos/ASIN/B0001106WU/icongroupinterna
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The Official Patient's Sourcebook on Antenatal Corticosteroid Therapy by Icon Health Publications; ISBN: 0597831327; http://www.amazon.com/exec/obidos/ASIN/0597831327/icongroupinterna
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Topical Corticosteroid Therapy: A Novel Approach to Safer Drugs by Christophers Enno; ISBN: 0881674478; http://www.amazon.com/exec/obidos/ASIN/0881674478/icongroupinterna
Chapters on Corticosteroids In order to find chapters that specifically relate to corticosteroids, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and corticosteroids 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 “corticosteroids” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on corticosteroids:
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Corticosteroids in PBC Source: in Lindor, K.D.; Heathcote, E.J.; Poupon, R., eds. Primary Biliary Cirrhosis: From Pathogenesis to Clinical Treatment. Boston, MA: Kluwer Academic Publishers. 1998. p. 130-137. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail:
[email protected]. Website: www.wkap.nl. Summary: Primary biliary cirrhosis (PBC) is a chronic cholestasic (lack of bile flow) liver disease of unknown etiology (cause), although the association with a large number of autoimmune disorders suggests that the disease may be of autoimmune origin. The disease usually affects middle aged women and progresses from asymptomatic disease with only laboratory abnormalities to a severe cholestatic disease with deep jaundice, xanthomas (fatty tumors in the skin), portal hypertension (high blood pressure), and eventually liver failure. This chapter on the use of corticosteroids to treat PBC is from a monograph that reprints papers from a conference held in November 1997 in Chicago, Illinois, on the clinical features (symptoms), pathogenesis, and treatment of PBC. Among the numerous drugs that have been evaluated for therapy of PBC, corticosteroids were not only the first to be used, but also the first to be considered unsuitable. During recent years, however, recognition of the partial efficacy of bile acid treatment, a better understanding of the dangers associated with steroid treatment, the introduction of improved tools for monitoring bone mass, and the development of effective therapy for treating bone loss have all contributed to a renewed interest in corticosteroids as therapeutic agents in PBC. The author concludes that three randomized controlled trials have shown that corticosteroids, either as monotherapy or combined with ursodeoxycholic acid (UDCA), exert favorable treatment effects in PBC. However, corticosteroids are only partially effective and do not seem able to induce clinical or biochemical remission in most patients. The author calls for additional studies, probably combining drugs with different modes of action in a combined treatment regimen. 2 figures. 1 table. 22 references.
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Appropriate Use of Corticosteroids in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 363-366. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of corticosteroids in managing inflammatory bowel disease (IBD) is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as IBD. Glucocorticoids are a mainstay for the treatment of severe IBD. The efficacy of corticosteroids to induce remission in both CD and Ulcerative Colitis (UC) has been well established in large randomized controlled trials. At times, a focus on adverse events has diminished the recognition of the usefulness of corticosteroids. The authors suggest approaches for the appropriate use of corticosteroids, including corticosteroid-sparing strategies, in patients with IBD. Corticosteroids used in the treatment of IBD are prednisone, prednisolone, methylprednisolone, and budesonide. Prednisone and prednisolone have comparable glucocorticoid potency, whereas methylprednisolone is slightly more potent. In IBD,
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their use should be restricted to severe, active disease, with the aim of inducing remission. Simple dosing considerations can decrease the possibility of serious side effects. For example, steroids should be given as a single morning dose to coincide with the natural circadian rhythm of endogenous (naturally occurring in the body) corticosteroids. Corticosteroid sparing strategies incorporate the use of nutrition, budesonide, aminosalicylates, antibiotics, azathioprine and 6 mercaptopurine (immunomodulators), methotrexate, cyclosporine, and anti-tumor necrosis factor alpha. 13 references. •
Systemic Corticosteroids in Inflammatory Bowel Disease Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 127-131. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of systemic corticosteroids in the treatment of ulcerative colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). Any therapy in UC must be considered with respect to its use in acute relapse, maintenance, and with chronic continuous (chronic active colitis) or frequently relapsing colitis. Corticosteroid therapy in UC may be initiated topically or systemically, and systemic treatment may be given orally or parenterally (outside the gastrointestinal tract, e.g., intravenous or intramuscular). Systemic administration may be combined with local therapy; systemic corticosteroids may be combined with 5-ASA preparations, again either topically, orally, or both, and occasionally with immunosuppression. Different systemic corticosteroid preparations are available, with similar anti-inflammatory effects, but with some differences in potency and tendency to cause side effects. Despite the relative homogeneity of patients in UC as a clinical group (at least in comparison with Crohn's disease), there are different scenarios of disease onset, activity, severity, and distribution. With this substantial number of variables, despite a number of clinical trials performed since those that initially established the value of corticosteroids, there remain extensive areas in which there is no firm evidence to guide management. This chapter briefly surveys those corticosteroids available for systemic use before considering practicalities of use in patients with various categories of UC. 10 references.
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Topically Active Corticosteroids for Colitis Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 73-76. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: This chapter on the use of topically active corticosteroids for treating colitis is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel disease (IBD). UC universally involves the rectum, but the proximal extent (how far it goes) of the disease is variable. When
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inflammation is limited to the rectum (proctitis) or to the sigmoid colon (proctosigmoiditis), the symptoms of urgency, tenesmus (straining to defecate), and bleeding cause substantial impact on daily activities, but systemic complications are lower when compared to panulcerative colitis. Topical administration of corticosteroids has been a mainstay of primary therapy for distal ulcerative colitis over several decades and also is a useful adjunct to oral therapy for more extensive disease. However, conventional corticosteroids may be associated with a spectrum of undesirable side effects and thus newer steroid formulations have emerged that provide advantages over conventional steroid preparations. The composite clinical experience indicates that topical 5-ASA (aminosalicylates) preparations will usually provide greater efficacy for distal ulcerative colitis. However, in the patient who is refractory to 5-ASA therapy or shows true 5-ASA sensitivity, topical hydrocortisone foam or budesonide may prove to be useful. Further refinements of the colonic release systems for oral budesonide enterocapsules (taken orally, but the drug is not released from the capsule until it reaches the intestine or colon) may be of benefit to patients with more extensive ulcerative colitis. 11 references.
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CHAPTER 7. PERIODICALS CORTICOSTEROIDS
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover corticosteroids.
News Services and Press Releases One of the simplest ways of tracking press releases on corticosteroids is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “corticosteroids” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to corticosteroids. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “corticosteroids” (or synonyms). The following was recently listed in this archive for corticosteroids: •
Mood disorders common among long-term corticosteroid users Source: Reuters Industry Breifing Date: May 28, 2004
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High-dose inhaled corticosteroids increase fracture risk in COPD Source: Reuters Industry Breifing Date: April 05, 2004
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Long-term use of corticosteroids is not associated with fracture risk Source: Reuters Industry Breifing Date: January 15, 2004
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Delayed corticosteroid allergy occasionally seen in asthmatics Source: Reuters Industry Breifing Date: December 22, 2003
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Smoking impairs efficacy of oral corticosteroid treatment in asthmatics Source: Reuters Industry Breifing Date: December 19, 2003
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Inhaled corticosteroids unlikely to have a major impact on BMD Source: Reuters Medical News Date: October 27, 2003
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Inhaled corticosteroids as effective as oral in pediatric asthma emergencies Source: Reuters Industry Breifing Date: October 02, 2003
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Systemic corticosteroids quell pediatric asthma exacerbations Source: Reuters Medical News Date: August 11, 2003 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “corticosteroids” (or synonyms) into the search box, and click on “Search News.” As this service is technology
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oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “corticosteroids” (or synonyms). If you know the name of a company that is relevant to corticosteroids, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “corticosteroids” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “corticosteroids” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on corticosteroids: •
Oral Lichen Planus Source: Oral Care Report. 11(4): 7. 2001. Contact: Available from Oral Care Report. c/o Dr. Chester W. Douglass, Department of Oral Health Policy, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115. Fax (617) 432-0047. E-mail:
[email protected]. Website: www.colgateprofessional.com (full-text available online). Summary: This brief article reviews oral lichen planus (OLP), a chronic, autoimmune disease that affects the oral mucosa. OLP manifests as mucosal lesions that vary in morphology (shape) and severity. Three different types of OLP are recognized: reticular, atrophic, and erosive. As the most severe form of the disease, erosive OLP can cause considerable pain, interfere with eating, and reduce the quality of life. The author summarizes treatment options, anticipated response to treatment, and side effects. There is currently no cure for OLP; standard treatment with topical and systemic corticosteroids is aimed at symptomatic relief. Patients with OLP must be followed closely, not only because of possible treatment side effects, but because they have a slightly increased risk of developing squamous cell carcinoma. 1 figure. 1 reference.
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Medications and Their Effects on the Voice Source: Voice Foundation Newsletter. 4(3): 1, 5-6. October 1998. Contact: Available from Voice Foundation. 1721 Pine Street, Philadelphia, PA 19103. (215) 735-7999. Fax (215) 735-9293. E-mail:
[email protected]. Summary: This newsletter article familiarizes voice professionals with the potential vocal risks of drug use. The author contends that virtually all medications have some laryngeal effect. In many instances, the effects are clinically insignificant. However, some common medications have substantial impact upon the voice, and all voice professionals should be familiar with drug-induced phenomena that may alter vocal function. The author briefly reviews the possible effects of antibiotics, anti-viral agents, antihistamines, mucolytic and wetting agents, diuretics and other nonsteroid medications for edema, decongestants, corticosteroids, sprays, mists and inhalants, antitussive medications, and antihypertensive agents. This article represents only the first half of the material; the information is continued in the January 1999 edition of the newsletter.
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Maybe It Isn't Gluten: Persistent 'Symptoms' May Be Caused by Gluten. Then Again, Maybe Not Source: Gluten-Free Living. 5(6): 7, 11. November-December 2000. Contact: Available from Gluten-Free Living. P.O. Box 105, Hastings-On-Hudson, NY 10706. (914) 969-2018. E-mail:
[email protected]. Website: www.celiac.com. Summary: This newsletter article reviews some of the symptoms that people with gluten intolerance may experience, even while carefully following a gluten free diet. The author cautions that some people with celiac disease (gluten intolerance) get so wrapped up in their diagnosis and in following the gluten free diet, that they forget there are other problems that can contribute to or worsen gastrointestinal symptoms. The author discusses disacharridase intolerance, pancreatic insufficiency, soy allergy, microscopic colitis, and refractory sprue (celiac disease that does not respond to a gluten free diet; it is very uncommon). Lactose intolerance (a type of disacharridase intolerance) is a common problem for celiac disease, particularly in those recently diagnosed in whom the intestinal lining has not yet healed with the use of diet therapy. Pancreatic insufficiency can occur from malnutrition caused by celiac disease. Most physicians diagnose pancreatic insufficiency by assessing the patient's clinical response to a trial of pancreatic enzyme replacement. An allergy to soy may produce gastrointestinal symptoms; it can also produce skin or respiratory reactions. Once soy is eliminated from the diet, the symptoms are relieved. Microscopic colitis (collagenous colitis and lymphocytic colitis) is an inflammatory disorder of the colon (large intestine) that causes watery, non bloody diarrhea. For patients with refractory sprue, prescription medications (corticosteroids or other immunosuppressive medications) are used, in conjunction with careful determination that nothing else is causing or contributing to the GI symptoms.
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Inflammatory Bowel Disease. Part II: Treatment Source: Intestinal Fortitude. 10(4): 1-3. 2000. Contact: Available from Intestinal Disease Foundation. 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5888.
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Summary: This newsletter article, the second in a two part series on inflammatory bowel disease (IBD), reviews the treatment options for people with the disease. The goals of therapy for IBD include symptom control and remission; good nutrition, for healing and to avoid additional problems relating to nutritional deficiencies; and quality of life, a common goal for all of the therapies used, including medications, coping techniques, and surgeries. For ulcerative colitis (UC) patients, removal of the colon produces a cure. It is major surgery, however, and for that reason needs to be carefully considered. Surgery for Crohn's disease (CD) is usually done to treat obstructions (from strictures), infections (abscesses), or non healing fistulas. There is a 10 percent chance per year of recurrence of the CD following surgery, but use of medications, along with surgery, may help reduce the odds. The author reviews four traditional therapies for IBD: 5 aminosalicylates, antibiotics, corticosteroids, and immunomodulators. The authors also considers a new therapy, infliximab (Remicade), a medication that works on a cellular level to prevent inflammation and was recently approved by the FDA for treatment of CD. The future treatment of UC and CD will involve medications that better target the immune chemicals responsible for inflammation. For now, the treatment of IBD remains a multidisciplinary approach (medical, surgical, and nutritional) aimed at controlling symptoms and maintaining wellness.
Academic Periodicals covering Corticosteroids Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to corticosteroids. In addition to these sources, you can search for articles covering corticosteroids that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for corticosteroids. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with corticosteroids. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to corticosteroids: Clioquinol and Hydrocortisone •
Topical - U.S. Brands: Vioform-Hydrocortisone Cream; Vioform-Hydrocortisone Lotion; Vioform-Hydrocortisone Mild Cream; Vioform-Hydrocortisone Mild Ointment; Vioform-Hydrocortisone Ointment http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202148.html
Clotrimazole and Betamethasone •
Topical - U.S. Brands: Lotrisone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202156.html
Colistin, Neomycin, and Hydrocortisone •
Otic - U.S. Brands: Coly-Mycin S Otic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202162.html
Corticosteroids •
Dental - U.S. Brands: Kenalog in Orabase; Orabase-HCA; Oracort; Oralone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202010.html
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Inhalation - U.S. Brands: AeroBid; AeroBid-M; Azmacort; Beclovent; Pulmicort Respules; Pulmicort Turbuhaler; Qvar; Vanceril; Vanceril 84 mcg Double Strength http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202011.html
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Nasal - U.S. Brands: Beconase; Beconase AQ; Dexacort Turbinaire; Flonase; Nasacort; Nasacort AQ; Nasalide; Nasarel; Nasonex; Rhinocort; Vancenase; Vancenase AQ 84 mcg; Vancenase pockethaler http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202012.html
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Ophthalmic - U.S. Brands: AK-Dex; AK-Pred; AK-Tate; Baldex; Decadron; Dexair; Dexotic; Econopred; Econopred Plus; Eflone; Flarex; Fluor-Op; FML Forte; FML Liquifilm; FML S.O.P.; HMS Liquifilm; Inflamase Forte; Inflamase Mild; I-Pred; Lite Pred; Maxidex; Ocu-Dex; Ocu-Pred; Ocu-Pred Forte; Ocu-PredA; Pred Forte; Pred Mild; Predair; Predair A; Predair Forte; Storz-Dexa; Ultra Pred http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202013.html
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Otic - U.S. Brands: Decadron http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202014.html
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Rectal - U.S. Brands: Anucort-HC; Anu-Med HC; Anuprep HC; Anusol-HC; Anutone-HC; Anuzone-HC; Cort-Dome; Cortenema; Cortifoam; Hemorrhoidal HC; Hemril-HC Uniserts; Proctocort; Proctosol-HC; Rectasol-HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203366.html
Corticosteroids and Acetic Acid •
Otic - U.S. Brands: VoSol HC http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202017.html
Corticosteroids Glucocorticoid Effects •
Systemic - U.S. Brands: Acetocot; A-hydroCort; Amcort; A-MethaPred; Aristocort; Aristocort Forte; Aristopak; Aristospan; Articulose-50; Articulose-
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L.A.; Celestone; Celestone Phosphate; Celestone Soluspan; Cinalone 40; Cinonide 40; Clinacort; Clinalog; Cordrol; Cortastat; Cortastat 10; Cortastat LA; Cortef; Cortone Acetate; Cotolone; Dalalone; Dalalone D.P.; Dalalone L.A.; Decadrol; Decadron; Decadron Elixir; Decadron Phosphate; Decadron-LA; Decaject; Decaject-LA; Delta-Cortef; Deltasone; DepMedalone 40; DepMedalone 80; Depoject-40; Depoject-80; Depo-Medrol; Depopred; Depo-Predate; Dexacorten; Dexacorten-LA; Dexamethasone Intensol; Dexasone; Dexasone L.A.; Dexone; Dexone 0.75; Dexone 1.5; Dexone 4; Dexone LA; Duralone-40; Duralone-80; Hexadrol; Hexadrol Phosphate; Hydrocortone; Hydrocortone Acetate; Hydrocortone Phosphate; Kenacort; Kenacort Diacetate; Kenaject-40; Kenalog-10; Kenalog-40; Ken-Jec 40; Key-Pred; Key-Pred SP; Liquid Pred; Med-Jec-40; Medralone 80; Medrol; Meprolone; Methacort 40; Methacort 80; Methylcotolone; Meticorten; Mymethasone; Nor-Pred T.B.A.; Orasone 1; Orasone 10; Orasone 20; Orasone 5; Orasone 50; Pediapred; Predacort 50; Predacorten; Predacorten 80; Predalone 50; Predalone T.B.A.; Predate S; Predate TBA; Predate-50; Predcor-25; Predcor-50; Predcor-TBA; Predicort-RP; Pred-Ject-50; Prednicot; Prednisone Intensol; Pred-Pak 45; Pred-Pak 79; Prelone; Primethasone; Robalog; Selestoject; Solu-Cortef; Solu-Medrol; Solurex; Solurex LA; Sterapred; Sterapred DS; Tac-3; Tramacort-D; Triam-A; Triam-Forte; Triamolone 40; Triamonide 40; Tri-Kort; Trilog; Trilone; Tristoject http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202018.html Corticosteroids Low Potency •
Topical - U.S. Brands: 9-1-1; Aclovate; Acticort 100; Aeroseb-Dex; Aeroseb-HC; Ala-Cort; Ala-Scalp HP; Allercort; Alphaderm; Bactine; Beta-HC; CaldeCORT Anti-Itch; CaldeCORT Light; Carmol-HC; Cetacort; Cloderm; Cortaid; CortDome; Cortef Feminine Itch; Corticaine; Cortifair; Cortril; Decaderm; Decadron; Decaspray; Delacort; Dermacort; Dermarest DriCort; DermiCort; Dermtex HC; DesOwen; Epifoam; FoilleCort; Gly-Cort; Gynecort; Gynecort 10; Hi-Cor 1.0; HiCor 2.5; Hydro-Tex; Hytone; LactiCare-HC; Lanacort; Lanacort 10; Lemoderm; Maximum Strength Cortaid; MyCort; Nutracort; Penecort; Pentacort; PharmaCort; Rederm; Rhulicort; S-T Cort; Synacort; Texacort; Tridesilon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202907.html
Corticosteroids Medium to Very High Potency •
Topical - U.S. Brands: Alphatrex; Aristocort; Aristocort A; Betatrex; Beta-Val; Bio-Syn; Cordran; Cordran SP; Cormax; Cutivate; Cyclocort; Delta-Tritex; Dermabet; Dermatop; Diprolene; Diprolene AF; Diprosone; Elocon; Florone; Florone E; Fluocet; Fluocin; Fluonid; Flurosyn; Flutex; Halog; Halog-E; Kenac; Kenalog; Kenalog-H; Kenonel; Licon; Lidex; Lidex-E; Locoid; Luxiq; Maxiflor; Maxivate; Olux; Pandel; Psorcon; Synalar; Synalar-HP; Synemol; Teladar; Temovate; Temovate E; Temovate Scalp Application; Topicort; Topicort LP; Triacet; Triderm; Ultravate; Uticort; Valisone; Valisone Reduced Strength; Valnac; Westcort http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202016.html
Cromolyn •
Inhalation - U.S. Brands: Intal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202166.html
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Docetaxel •
Systemic - U.S. Brands: Taxotere http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202920.html
Dornase Alfa •
Inhalation - U.S. Brands: Pulmozyme http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202710.html
Fludrocortisone •
Systemic - U.S. Brands: Florinef http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202244.html
Fluticasone •
Inhalation-Local - U.S. Brands: Flovent; Flovent Rotadisk http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203649.html
•
Nasal - U.S. Brands: Flonase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203588.html
Fluticasone and Salmeterol •
Inhalation-Local - U.S. Brands: Advair Diskus http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500235.html
Formoterol •
Inhalation-Local - U.S. Brands: Foradil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500269.html
Ivermectin •
Systemic - U.S. Brands: Stromectol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202311.html
Loteprednol •
Ophthalmic - U.S. Brands: Alrex; Lotemax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203541.html
Metyrapone •
Systemic - U.S. Brands: Metopirone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202367.html
Mometasone •
Nasal - U.S. Brands: Nasonex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203589.html
Nedocromil •
Inhalation - U.S. Brands: Tilade http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202681.html
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Neomycin, Polymyxin B, and Hydrocortisone •
Ophthalmic - U.S. Brands: Ak-Spore H.C. Ophthalmic Suspension; Cortisporin Ophthalmic Suspension http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202402.html
•
Otic - U.S. Brands: AK-Spore HC Otic; Antibiotic Ear; Cortatrigen Ear; Cortatrigen Modified Ear Drops; Cort-Biotic; Cortisporin; Cortomycin; Drotic; Ear-Eze; LazerSporin-C; Masporin Otic; Octicair; Octigen; Otic-Care; Otic-Care Ear; Otimar; Otisan; Otocidin; Otocort; Pediotic; UAD Otic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202403.html
Nystatin and Triamcinolone •
Topical - U.S. Brands: Dermacomb; Myco II; Mycobiotic II; Mycogen II; Mycolog II; Myco-Triacet II; Mykacet; Mykacet II; Mytrex; Tristatin II http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202420.html
Rimexolone •
Ophthalmic - U.S. Brands: Vexol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203590.html
Risedronate •
Systemic - U.S. Brands: Actonel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203554.html
Sirolimus •
Systemic - U.S. Brands: Rapamune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500028.html
Thiabendazole •
Systemic - U.S. Brands: Mintezol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202558.html
Tobramycin And Dexamethasone •
Ophthalmic - U.S. Brands: Tobradex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203776.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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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
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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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/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
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 “corticosteroids” (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 151596 460 978 162 3447 156643
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 “corticosteroids” (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 corticosteroids 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 corticosteroids. 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 corticosteroids. 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 “corticosteroids”:
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Addison's Disease http://www.nlm.nih.gov/medlineplus/addisonsdisease.html Adrenal Gland Disorders http://www.nlm.nih.gov/medlineplus/adrenalglanddisorders.html Alpha-1 Antitrypsin Deficiency http://www.nlm.nih.gov/medlineplus/alpha1antitrypsindeficiency.html Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Asthma http://www.nlm.nih.gov/medlineplus/asthma.html Asthma in Children http://www.nlm.nih.gov/medlineplus/asthmainchildren.html Autoimmune Diseases http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html COPD http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.t ml Crohn's Disease http://www.nlm.nih.gov/medlineplus/crohnsdisease.html Diabetic Eye Problems http://www.nlm.nih.gov/medlineplus/diabeticeyeproblems.html Drug and Medical Device Safety http://www.nlm.nih.gov/medlineplus/drugandmedicaldevicesafety.html Endocrine Diseases http://www.nlm.nih.gov/medlineplus/endocrinediseases.html Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Medicines http://www.nlm.nih.gov/medlineplus/medicines.html Nose Disorders http://www.nlm.nih.gov/medlineplus/nosedisorders.html Premature Babies http://www.nlm.nih.gov/medlineplus/prematurebabies.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html Skin Diseases http://www.nlm.nih.gov/medlineplus/skindiseases.html Smallpox http://www.nlm.nih.gov/medlineplus/smallpox.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html
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Vaginal Diseases http://www.nlm.nih.gov/medlineplus/vaginaldiseases.html Vitiligo http://www.nlm.nih.gov/medlineplus/vitiligo.html 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 corticosteroids. 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: •
Behcet's Disease: What You Should Know: Symptoms, Causes and Treatment Source: Minneapolis, MN: American Behcet's Disease Association. 1991. 4 p. Contact: Available from American Behcet's Disease Association. P.O. Box 54063, Minneapolis, MN 55454-0063. (800) 7BEHCETS. PRICE: Single copy free; $0.75 for each additional copy. Summary: Behcet's disease is a rare, chronic, lifelong disorder that involves inflammation of blood vessels throughout the body, causing recurrent oral ulcerations resembling canker sores, recurrent genital ulcers, and inflammation inside of the eyes. This brochure provides general patient education information on the symptoms, causes, and treatment of Behcet's disease. Topics covered include the specific symptoms, the role of the immune system in Behcet's, primary care and specialists involved in patient care management; drug therapy, including topical corticosteroids, anti-inflammatory drugs, and immunosuppressive drugs; and the prognosis for people with Behcet's.
•
Childhood Nephrotic Syndrome Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH). 2000. 4 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301)634-0716. E-mail:
[email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available online at no charge; single copy free; bulk orders available. Order number: KU-141.
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Summary: Childhood nephrotic syndrome includes high levels of protein in the urine, low levels of protein in the blood, and swelling resulting from buildup of salt (sodium) and water. The nephrotic syndrome can be the first sign of a disease that damages the tiny blood filtering units (glomeruli) in the kidneys, where urine is made. This fact sheet offers information about childhood nephrotic syndrome, how it is diagnosed, and current research efforts to better understand this condition. The syndrome is usually diagnosed with urine testing (to check for protein) and blood tests (to see how well the kidneys are removing wastes); kidney biopsy may also be indicated. The most common form of the nephrotic syndrome in children is called minimal change disease (children diagnosed with this have normal or nearly normal biopsies). Minimal change disease is usually treated with drugs, including corticosteroids and diuretics. In about 20 percent of children with the nephrotic syndrome, the kidney biopsy reveals scarring or deposits in the glomeruli. Treatment for these children can include ACE inhibitors which help prevent protein from leaking into the urine and keep the kidneys from being damaged. The fact sheet concludes with a list of organizations that can provide readers with more information and a brief description of the activities of the NKUDIC. •
Fatty Liver Source: Cedar Grove, NJ: American Liver Foundation. 1997. [2 p.]. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) 4HEP-ABC. Fax (973) 256-3214. E-mail:
[email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: Fatty liver is the accumulation of fat in liver cells (fatty infiltration of the liver). Fat accumulates in the liver usually in connection with heavy use of alcohol, extreme weight gain, or diabetes mellitus. Fatty liver can also occur with poor diet and certain illnesses, such as tuberculosis, intestinal bypass surgery for obesity, and certain drugs such as corticosteroids. This fact sheet reviews fatty liver. Written in a question and answer format, the fact sheet covers the causes of fatty liver, symptoms, diagnostic tests that may be used to confirm the condition, how fatty liver occurs, and treatment options. The author concludes that simple fatty liver does not require treatment, since it does not result in damage to liver cells or clinical disease. The treatment of other types of fatty liver is related to the cause. The fact sheet concludes with the contact information for the American Liver Foundation, a nonprofit, national voluntary health organization (www.liverfoundation.org).
•
Drugs Used in IBD Source: St. Albans, England: National Association for Colitis and Crohn's Disease. 2000. 20 p. Contact: Available from National Association for Colitis and Crohn's Disease (NACC). 4 Beaumont House, Sutton Road, St. Albans, Hertfordshire, AL1 5 HH. 01727-844296. Fax 01727-862550. E-mail:
[email protected]. Website: www.nacc.org.uk. PRICE: Single copy free to members. Summary: This booklet helps people with inflammatory bowel disease (IBD) understand the nature and purpose of different drugs used in treatment. IBD is the general term used for ulcerative colitis (UC) and Crohn's disease (CD). The booklet covers how drugs are taken (topical, oral, and intravenous), antiinflammatory drugs, corticosteroids, aminosalicylates (5 ASAs), immunomodulators and
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immunosuppressants, antibiotics, symptomatic drugs, the role of nutritional support, and special circumstances, including pregnancy and breastfeeding, osteoporosis, children, and the use of alternative and complementary therapies. Specific drugs covered include azathioprine (Imuran), 6 mercaptopurine (Purinethol), cyclosporin (Sandimmune), methotrexate, infliximab (Remicade), metronidazole (Flagyl), ciprofloxacin, clarithromycin, anti-myobacterium (anti tuberculous) therapy, antidiarreals, antimotility drugs, bile salt drugs, bulking agents, and analgesics (pain killers). Since UC and CD are inflammatory diseases, many antiinflammatory drugs are used to combat or dampen down the inflammation. Antiobiotics that kill or inhibit bacteria can also play a role in treatment, particularly for CD. Other drugs may help to reduce symptoms such as diarrhea or pain, but do not reduce inflammation. Nutritional support can be important in IBD. Supplements such as iron, minerals, and vitamins may be prescribed to replace important body chemicals (nutrients) that are lost or cannot be absorbed by the intestines of people who have Crohn's or UC. Special diets can also play a part in treatment for some patients. The booklet concludes by encouraging patients to work closely with their doctor to learn about and implement the drug therapy options that are available. The booklet lists related information and support organizations in England. 1 figure. 2 tables. •
Q and A: About Crohn's Disease Source: New York, NY: Crohn's and Colitis Foundation of America. 2002. 11 p. Contact: Available from Crohn's and Colitis Foundation of America (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 932-2423. E-mail:
[email protected]. Website: www.ccfa.org. PRICE: Single copy free. Summary: This brochure answers commonly asked questions about Crohn's disease, a serious inflammatory disease of the gastrointestinal (GI) tract. Crohn's disease usually causes diarrhea, crampy abdominal pain, often fever, and at times rectal bleeding. In Crohn's disease (compared to the other inflammatory bowel disease, ulcerative colitis), all layers of the intestine are involved, and there can be normal healthy bowel in between patches of diseased bowel. The diagnosis of Crohn's disease is suggested by the patient history (signs and symptoms); additional testing that may be used include barium x-rays of the upper and lower GI tract, flexible sigmoidoscopy, and sometimes colonoscopy. Laboratory tests are also helpful and include evaluation of the blood and stool. The goals of medical treatment are to suppress the inflammatory response to permit healing of tissue, and to relieve the symptoms of fever, diarrhea, and abdominal pain. Several groups of drugs are used: aminosalicylates, corticosteroids, immune modifiers, and antibiotics. Surgery becomes necessary in Crohn's disease when medication can no longer control the symptoms, or when there is an intestinal obstruction or other complication. Good nutrition is essential in this disease, which is characterized by reduced appetite, poor absorption, and diarrhea, all of which rob the body of fluids, nutrients, vitamins, and minerals. Most people with the illness continue to lead useful and productive lives, even though they may be hospitalized from time to time, and may need to take medications. The brochure concludes with a brief description of current research efforts and a detailed glossary of related terms. 1 figure.
•
Living with Inflammatory Bowel Disease: Your Illness and Its Treatment Source: San Bruno, CA: StayWell Company. 1998. 16 p.
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Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. PRICE: $1.60 plus shipping and handling; bulk copies available. Order number 11003. Summary: This brochure describes inflammatory bowel disease (IBD), characterized by inflammation (irritation and swelling) of the digestive tract. IBD has two subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis occurs in the rectum and sometimes in the colon; Crohn's disease can occur anywhere from the mouth to the anus, but usually affects the last part of the small intestine. The brochure describes how the digestive tract works, how IBD affects the digestive tract, diagnosing and monitoring IBD, treating IBD with medication, managing daily life, managing nutrition, and surgery for IBD. The symptoms of Crohn's can include abdominal pain and bloating after meals, sores in the anal area, high fever and chills, loss of appetite (possible weight loss), bloody diarrhea, and nausea or vomiting. Diagnostic tests that may be used to confirm Crohn's disease include barium enema, upper GI series, and small bowel series, endoscopy, blood or stool tests, and CT scan. The symptoms of UC can include frequent, loose bowel movements; blood and pus in stools; rectal bleeding; feeling of incomplete bowel movement; urgency; severe straining with bowel movement; joint pain; and rectal pain that comes and goes. Diagnostic tests that may be used to confirm UC include endoscopy, biopsy, blood or stool tests, and xrays of the colon. Drug therapy for IBD can include antiinflammatory agents, corticosteroids, immunosuppressive agents, and antibiotics. Readers are advised to monitor their dietary habits and take note of which foods seem to be problematic. Surgical options described include limited bowel resection, ileoanal pouch, proctocolectomy with permanent ileostomy, continent ileostomy, strictureplasty, and anal fistula surgery; each technique is illustrated with a simple line drawing. The brochure also explains what patients can expect before and after surgery for IBD. The brochure encourages readers to work closely with their health care providers and to seek out support groups to talk with others who are dealing with IBD. The toll free telephone numbers of the Crohn's and Colitis Foundation (800-9322423) and the United Ostomy Association (800-826-0826) are provided. The brochure is illustrated with full color drawings. 19 figures. •
What is Lupus? Source: Rockville, MD: Lupus Foundation of America, Inc. 1996. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800)558-0121 or (301) 670-9292. PRICE: Single copy free. Summary: This brochure describes lupus, a chronic autoimmune disease which causes inflammation of various parts of the body, especially the skin, joints, blood, and kidneys. The brochure reviews the three types of lupus: discoid, systemic, and druginduced. The cause of lupus is unknown, but environmental and genetic factors are involved. Some of the environmental factors that may trigger the disease are infections, antibiotics (especially those in the sulfa and penicillin groups), ultraviolet light, extreme stress, and certain drugs. The brochure discusses pregnancy and lupus, symptoms of the disease, the 11 criteria used for the diagnosis of lupus erythematosus, laboratory tests used in diagnosis, flare-ups, treatment options, the role of nutrition and diet, and prognostic considerations. Treatments discussed include nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, corticosteroids, anti-malarials, and cytotoxic drugs. With early diagnosis and current methods of therapy, 80 to 90 percent of people with lupus can look forward to a normal lifespan. This likelihood is increased if they follow the instructions of their physician, take their medication(s) as prescribed, and know when to seek help for unexpected side effects of a medication or a new
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manifestation of lupus. The brochure concludes with a description of the goals and activities of the Lupus Foundation of America (LFA). The LFA assists local chapters in their efforts to provide supportive services to individuals living with lupus, educates the public about lupus, and supports research into the cause and cure of lupus. 2 tables. (AA-M). •
What Do I Need to Know About Preventing the Complications of Chronic Kidney Disease? Source: Rockville, MD: American Kidney Fund. 2002. 32 p. Contact: Available from American Kidney Fund (AKF). 6110 Executive Boulevard, Suite 1010, Rockville, MD 20852. (8000) 638-8299 or (301) 881-3052 Fax (301) 881-0898. E-mail:
[email protected]. Website: www.kidneyfund.org. PRICE: 1-10 copies free; additional copies available at cost. Summary: This brochure helps readers newly diagnosed with renal insufficiency or early chronic kidney disease (CKD) understand how to take care of themselves and prevent the complications common to CKD. The brochure introduces readers to kidney disease, then discusses treatment options, the role of diet in treatment and prevention, possible complications associated with kidney disease, and the different types of doctors kidney disease patients normally encounter. Specific topics include a description of the physiology and function of the kidneys, symptoms of kidney disease, glomerular filtration rate (GFR, a measure of kidney function), the role of blood pressure control, diabetes control (when applicable), corticosteroids or other special medications, the need to avoid certain medications, protein restriction, caloric intake, carbohydrates, fats, fluid restriction, sodium, potassium, phosphorus, anemia, measuring hemoglobin (red blood cells), hypertension, vitamins and minerals, acidosis, and osteodystrophy (bone disease). The booklet includes sample menus, numerous charts of information, a summary of the concepts presented, and a glossary of terms. A list of resource organizations is also included, for readers wishing to obtain additional information. A reader's response questionnaire postage-paid postcard is appended to the brochure. 3 figures.
•
Medications for Inflammatory Bowel Disease Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. (CCFA). 199x. 20 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail:
[email protected] PRICE: Single copy free. Summary: This brochure reviews for health professionals the available information on both the standard drug therapy for inflammatory bowel disease (IBD) and the agents under investigation. Topics include 5-ASA agents, including sulfasalazine, topical and oral forms of aminosalicylates, slow-release agents (mesalamine), chemically linked agents (olsalazine), and the side effects of these drugs; corticosteroids in topical, oral, parenteral, and rapidly-metabolized forms; immunomodulators, including 6mercaptopurine and azathioprine, cyclosporin, and methotrexate; antibiotics, including metronidazole, ciproflaxin, and antituberculous agents; lipoxygenase inhibitors; nicotine; antidiarrheal agents, including loperamide, diphenoxylate with atropine, codeine, and deodorized tincture of opium; anticholinergic agents; psychotropic agents; miscellaneous agents that show potential benefit; and drugs that may exacerbate colitis.
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The brochure includes a section on the management of the pediatric patient, including the use of sulfasalazine, aminosalicylates, corticosteroids, immunomodulators, antibiotics, and antidiarrheal agents. It also addresses specific issues of adolescents. •
Crohn's Disease: Questions and Answers Source: Arlington Heights, IL: American Society of Colon and Rectal Surgeons. 1996. 2 p. Contact: Available from American Society of Colon and Rectal Surgeons. 85 West Algonquin Road, Suite 550, Arlington Heights, IL 60005. (800) 791-0001 or (847) 2909184. Fax (847) 290-9203. Price: Single copy free; bulk copies available. Summary: This brochure, from the American Society of Colon and Rectal Surgeons, provides basic information about Crohn's disease. Crohn's disease is a chronic inflammatory process primarily involving the intestinal tract. Crohn's disease most commonly affects the last part of the small intestine (ileum) and or the large intestine (colon and rectum). The brochure describes the symptoms of Crohn's disease, etiologic theories, and treatment options. Common Crohn's symptoms including cramping and abdominal pain, diarrhea, fever, weight loss, bloating, anal pain or drainage, skin lesions, rectal abscess, fissure, and joint pain. Initial treatment of Crohn's disease is almost always with medication, including corticosteroids and various antiinflammatory agents. In more advanced or complicated cases of Crohn's disease, surgery may be recommended. Emergency surgery is sometimes necessary when complications, such as a perforation of the intestine, obstruction of the bowel, or significant bleeding occur with Crohn's disease. The brochure notes that surgery is eventually required in up to three-fourths of all patients with Crohn's. Surgery often provides effective longterm relief of symptoms and frequently limits or eliminates the need for ongoing use of prescribed medications. The brochure concludes with a brief description of the specialty practiced by colon and rectal surgeons. 2 figures. (AA-M).
•
Peyronie's Disease Source: American Family Physician. 60(2): 554. August 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Also available at www.aafp.org/afp/990800ap/990800e.html. Summary: This patient education handout discusses Peyronie's disease, an acquired inflammatory condition of the penis associated with penile curvature and, in some cases, pain. It affects men primarily between 45 and 60 years of age, although an age range of 18 to 80 years has been reported. In some men, Peyronie's disease is a mild problem without symptoms. Other men with Peyronie's disease may have pain during erection or erections that aren't hard enough for sexual intercourse. Many cases resolve without treatment. Medical therapies include antioxidants (such as vitamin E and potassium aminobenzoate) and corticosteroids injected directly into the penis. The fact sheet encourages patients to work closely with their physician, particularly for dosing of medications. Surgery can be used for men who have bad pain during sexual intercourse; surgery is also used to place a penile implant (prosthesis) to help make the penis straighter and to help erections last longer.
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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 “corticosteroids” (or synonyms). The following was recently posted: •
Antenatal corticosteroids revisited: repeat courses Source: National Institute of Child Health and Human Development - Federal Government Agency [U.S.]; 2000 August 18; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2717&nbr=1943&a mp;string=corticosteroids
•
Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants Source: American Academy of Pediatrics - Medical Specialty Society; 2002 February; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3175&nbr=2401&a mp;string=corticosteroids
•
Practice parameter: the role of corticosteroids in the management of acute monosymptomatic optic neuritis. Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2000 June; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2831&nbr=2057&a mp;string=corticosteroids Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Antenatal Corticosteroids Revisited: Repeat Courses Summary: This NIH consensus statement covers the benefits and risks of repeat courses of antenatal corticosteroids. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6338 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 corticosteroids. 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
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professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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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 corticosteroids. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with corticosteroids. 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 corticosteroids. 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/.
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Simply type in “corticosteroids” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “corticosteroids”. 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 “corticosteroids” (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 “corticosteroids” (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/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
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
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on corticosteroids: •
Basic Guidelines for Corticosteroids Corticosteroids overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002582.htm Cortisol - urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003703.htm Cortisol level Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003693.htm
•
Signs & Symptoms for Corticosteroids Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm
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Deafness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Emesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Itching Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003217.htm Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Sleepiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Swelling in lower legs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •
Diagnostics and Tests for Corticosteroids 17-OHCS Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003459.htm ACTH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003695.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm Ulcers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003228.htm
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Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •
Background Topics for Corticosteroids Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Adrenal glands Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002219.htm Amino acids Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002222.htm Benign Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002236.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Immune response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Inflammatory response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Penis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002279.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm Vital signs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002341.htm
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Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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CORTICOSTEROIDS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 6-Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate. [NIH]
Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different
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from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
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Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] AFP: Alpha-fetoprotein. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU]
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Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amblyopia: A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivationinduced amblopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. Strabismus and refractive errors may cause this condition. Toxic amblyopia is a disorder of the optic nerve which is associated with alcoholism, tobacco smoking, and other toxins and as an adverse effect of the use of some medications. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH]
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Aminoglutethimide: An anticancer drug that belongs to the family of drugs called nonsteroidal aromatase inhibitors. Aminoglutethimide is used to decrease the production of sex hormones (estrogen or testosterone) and suppress the growth of tumors that need sex hormones to grow. [NIH] Aminoquinolines: Quinolines substituted in any position by one or more amino groups. [NIH]
Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anal Fistula: A channel that develops between the anus and the skin. Most fistulas are the result of an abscess (infection) that spreads to the skin. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH]
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Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anogenital: Pertaining to the anus and external genitals. [EU] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthracyclines: Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IgG whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc
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receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. [NIH] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihistamine: A drug that counteracts the action of histamine. The antihistamines are of two types. The conventional ones, as those used in allergies, block the H1 histamine receptors, whereas the others block the H2 receptors. Called also antihistaminic. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and
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febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antithymocyte globulin: A protein used to reduce the risk of or to treat graft-versus-host disease. [NIH] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]
Apnea: A transient absence of spontaneous respiration. [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] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus
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fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Asparaginase: A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic Eczema: Generic term for acute or chronic inflammatory conditions of the skin, typically erythematous, edematous, papular, vesicular, and crusting; often accompanied by sensations of itching and burning. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH]
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Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH]
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Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]
Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving
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chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blasts: Immature blood cells. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH]
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Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] 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] Blood-Aqueous Barrier: The selectively permeable barrier between the capillary bed in the ciliary body and the aqueous humor. It consists of two layers of epithelium joined at their apical surfaces by tight junctions. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blood-Retinal Barrier: Specialized nonfenestrated tightly-joined endothelial cells that form a transport barrier for certain substances between the retinal capillaries and the retinal tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH]
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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] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Provocation Tests: Tests involving inhalation of allergens (nebulized or in dust form), nebulized pharmacologically active solutions (e.g., histamine, methacholine), or control solutions, followed by assessment of respiratory function. These tests are used in the diagnosis of asthma. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bulking Agents: Laxatives that make bowel movements soft and easy to pass. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in
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many enzymatic processes. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carbonate Dehydratase: A zinc-containing enzyme of erythrocytes with molecular weight of 30 kD. It is among the most active of known enzymes and catalyzes the reversible hydration of carbon dioxide, which is significant in the transport of CO2 from the tissues to
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the lungs. The enzyme is inhibited by acetazolamide. EC 4.2.1.1. [NIH] Carbonic Anhydrase Inhibitors: A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of carbonic anhydrase (carbonate dehydratase). [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [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] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalepsy: A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with psychotic disorders (e.g., schizophrenia, catatonic), nervous system drug toxicity, and other conditions. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ,
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or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cat-Scratch Disease: A self-limiting bacterial infection of the regional lymph nodes caused by Afipia felis, a gram-negative bacterium recently identified by the Centers for Disease Control and Prevention and by Bartonella henselae. It usually arises one or more weeks following a feline scratch, with raised inflammatory nodules at the site of the scratch being the primary symptom. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter 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 Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in
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man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cerumen: The yellow or brown waxy secretions produced by vestigial apocrine sweat glands in the external ear canal. [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 relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [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] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Chloral Hydrate: A hypnotic and sedative used in the treatment of insomnia. The safety margin is too narrow for chloral hydrate to be used as a general anesthetic in humans, but it is commonly used for that purpose in animal experiments. It is no longer considered useful as an anti-anxiety medication. [NIH] Chlorambucil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Choleretic: A choleretic agent. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla.
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[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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [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] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Circumcision: Excision of the prepuce or part of it. [NIH]
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Cirrhosis: A type of chronic, progressive liver disease. [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] Cladribine: An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [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] Clobetasol: Topical corticosteroid that is absorbed faster than fluocinonide. It is used in psoriasis, but may cause marked adrenocortical suppression. [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] Closing Volume: The lung volume at which the dependent lung zones cease to ventilate presumably as a result of airway closure. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains
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knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all 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] Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [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
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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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized 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]
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Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condylomata Acuminata: Sexually transmitted form of anogenital warty growth caused by the human papillomaviruses. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]
Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continent Ileostomy: An operation to create a pouch from part of the small intestine. Stool that collects in the pouch is removed by inserting a small tube through an opening made in the abdomen. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [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] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]
Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral
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or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH]
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Cortodoxone: 17,21-Dihydroxypregn-4-ene-3,20-dione. A 17-hydroxycorticosteroid with glucocorticoid and anti-inflammatory activities. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom
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of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytopenia: A reduction in the number of blood 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] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decongestant: An agent that reduces congestion or swelling. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive
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stimuli from other neurons. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermatitis Herpetiformis: Rare, chronic, papulo-vesicular disease characterized by an intensely pruritic eruption consisting of various combinations of symmetrical, erythematous, papular, vesicular, or bullous lesions. The disease is strongly associated with the presence of HLA-B8 and HLA-DR3 antigens. A variety of different autoantibodies has been detected in small numbers in patients with dermatitis herpetiformis. [NIH] Dermatitis, Atopic: A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema. [NIH] Dermatitis, Contact: A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU]
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Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desiccation: Removal of moisture from a substance (chemical, food, tissue, etc.). [NIH] Desonide: A nonfluorinated corticosteroid anti-inflammatory agent used topically for dermatoses. [NIH] Desoximetasone: Topical anti-inflammatory glucocorticoid used in dermatoses, skin allergies, psoriasis, etc. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] 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] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH]
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Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenoxylate: A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discoid: Shaped like a disk. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic
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effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Dross: Residue remaining in an opium pipe which has been smoked; contains 50 % of the morphine present in the original drug. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]
Duodenum: The first part of the small intestine. [NIH]
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Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ear Diseases: Diseases of the ear, general or unspecified. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH]
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Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into
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the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Endotracheal intubation: Insertion of an airtube into the windpipe. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences,
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or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythrina: A genus of leguminous shrubs or trees, mainly tropical, yielding certain alkaloids, lectins, and other useful compounds. [NIH]
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Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]
Etretinate: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH]
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Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] 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] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of
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fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibrotic tissue: Inflamed tissue that has become scarred. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU]
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Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flexor: Muscles which flex a joint. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Flumethasone: An anti-inflammatory glucocorticoid used in veterinary practice. [NIH] Fluocinonide: A topical glucocorticoid used in the treatment of eczemas. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluorophotometry: Measurement of light given off by fluorescein in order to assess the integrity of various ocular barriers. The method is used to investigate the blood-aqueous barrier, blood-retinal barrier, aqueous flow measurements, corneal endothelial permeability, and tear flow dynamics. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Fluprednisolone: A synthetic glucocorticoid with anti-inflammatory properties. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH]
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Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]
Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fumigation: The application of smoke, vapor, or gas for the purpose of disinfecting or destroying pests or microorganisms. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Fungicide: An agent that destroys fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Fuzzy Logic: Approximate, quantitative reasoning that is concerned with the linguistic ambiguity which exists in natural or synthetic language. At its core are variables such as good, bad, and young as well as modifiers such as more, less, and very. These ordinary terms represent fuzzy sets in a particular problem. Fuzzy logic plays a key role in many medical expert systems. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored
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in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionectomy: Removal of an autonomic or sensory ganglion by any means. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gemtuzumab ozogamicin: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] 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] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of
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heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucaric Acid: A sugar acid derived from D-glucose in which both the aldehydic carbon atom and the carbon atom bearing the primary hydroxyl group are oxidized to carboxylic acid groups. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of
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glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH]
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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] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematemesis: The vomiting of blood. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]
Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH]
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Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocyte: A liver cell. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one
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generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hospital Mortality: A vital statistic measuring or recording the rate of death from any cause in hospitalized populations. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human
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gene has already been cloned and successfully expressed in bacteria. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperaldosteronism: Aldosteronism. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperemesis: Excessive vomiting. [EU] Hypericum: Genus of perennial plants in the family Clusiaceae (Hypericaceae). Herbal and homeopathic preparations are used for depression, neuralgias, and a variety of other
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conditions. Contains flavonoids, glycosides, mucilage, tannins, and volatile oils (oils, essential). [NIH] Hyperkeratosis: 1. Hypertrophy of the corneous layer of the skin. 2a. Any of various conditions marked by hyperkeratosis. 2b. A disease of cattle marked by thickening and wringling of the hide and formation of papillary outgrowths on the buccal mucous membranes, often accompanied by watery discharge from eyes and nose, diarrhoea, loss of condition, and abortion of pregnant animals, and now believed to result from ingestion of the chlorinated naphthalene of various lubricating oils. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [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] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypophyseal: Hypophysial. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU]
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Hypoxic: Having too little oxygen. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileitis: Inflammation of the ileum. [EU] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immortal: Stage when the mother cell and its descendants will multiply indefinitely. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH]
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Immunology: The study of the body's immune system. [NIH] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotent: Unable to have an erection adequate for sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] 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] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed
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by additional therapy to eliminate whatever cancer remains. [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infantile: Pertaining to an infant or to infancy. [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]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammation Mediators: The endogenous compounds that mediate inflammation (autacoids) and related exogenous compounds including the synthetic prostaglandins (prostaglandins, synthetic). [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [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] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role
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in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-15: Cytokine that stimulates the proliferation of T-lymphocytes and shares biological activities with IL-2. IL-15 also can induce B-lymphocyte proliferation and differentiation. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH]
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Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intertrigo: A superficial dermatitis occurring on skin surfaces in contact with each other, such as the axillae, neck creases, intergluteal fold, between the toes, etc. Obesity is a predisposing factor. The condition is caused by moisture and friction and is characterized by erythema, maceration, burning, and exudation. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestinal Obstruction: Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anus. [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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypotension: A condition in which there is a diminution or loss of muscular tonicity, in consequence of which the muscles may be stretched beyond their normal limits. [NIH]
Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [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]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from
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the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [NIH]
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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] Keratitis: Inflammation of the cornea. [NIH] Keratoacanthoma: A benign, non-neoplastic, usually self-limiting epithelial lesion closely resembling squamous cell carcinoma clinically and histopathologically. It occurs in solitary, multiple, and eruptive forms. The solitary and multiple forms occur on sunlight exposed areas and are identical histologically; they affect primarily white males. The eruptive form usually involves both sexes and appears as a generalized papular eruption. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketosteroids: Steroid derivatives formed by oxidation of a methyl group on the side chain or a methylene group in the ring skeleton to form a ketone. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+,
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catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [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] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU]
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Leukemia: Cancer of blood-forming tissue. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] Lichenification: Hypertrophy of the epidermis, resulting in thickening of the skin with exaggeration of the normal skin markings, giving the skin a leathery barklike appearance, which is caused by prolonged rubbing or scratching. It may arise on seemingly normal skin, or it may develop at the site of another pruritic cutaneous disorder. [EU] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] 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
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independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Local therapy: Treatment that affects cells in the tumor and the area close to it. [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]
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Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lung volume: The amount of air the lungs hold. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
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] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH]
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Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Maceration: The softening of a solid by soaking. In histology, the softening of a tissue by soaking, especially in acids, until the connective tissue fibres are so dissolved that the tissue components can be teased apart. In obstetrics, the degenerative changes with discoloration and softening of tissues, and eventual disintegration, of a fetus retained in the uterus after its death. [EU] Macroglia: A type of neuroglia composed of astrocytes. [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 computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marijuana Abuse: The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning. [NIH] Mass Media: Instruments or technological means of communication that reach large numbers of people with a common message: press, radio, television, etc. [NIH] Maternal Deprivation: Prolonged separation of the offspring from the mother. [NIH]
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Maternal Exposure: Exposure of the female parent, human or animal, to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals that may affect offspring. It includes pre-conception maternal exposure. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal
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tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Mercaptopurine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [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] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH]
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Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having the properties of, or resembling a mineralocorticoid. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [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] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]
Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH]
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Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] 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] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH]
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Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myositis: Inflammation of a voluntary muscle. [EU] Myxedema: A condition characterized by a dry, waxy type of swelling with abnormal deposits of mucin in the skin and other tissues. It is produced by a functional insufficiency of the thyroid gland, resulting in deficiency of thyroid hormone. The skin becomes puffy around the eyes and on the cheeks and the face is dull and expressionless with thickened nose and lips. The congenital form of the disease is cretinism. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit.
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Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nebulizer: A device used to turn liquid into a fine spray. [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] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Hepatitis: Irritation of the liver with no known cause. Occurs in newborn babies. Symptoms include jaundice and liver cell changes. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodermatitis: An extremely variable eczematous skin disease that is presumed to be a response to prolonged vigorous scratching, rubbing, or pinching to relieve intense pruritus. It varies in intensity, severity, course, and morphologic expression in different individuals. Neurodermatitis is believed by some to be psychogenic. The circumscribed or localized form is often referred to as lichen simplex chronicus. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH]
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Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neurovegetative: Pertaining to the vegetative (autonomic) nervous system. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Noxae: Agents capable of exerting a harmful effect on the body. [NIH]
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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] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of meta-
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rhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic disc: The circular area (disc) where the optic nerve connects to the retina. [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] Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [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] Osteodystrophy: Defective bone formation. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Otitis Media with Effusion: Inflammation of the middle ear with a clear pale yellowcolored transudate. [NIH] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from
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the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the
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duodenum. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]
Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papilledema: Swelling around the optic disk. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [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] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH]
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Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] 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 Care Management: Generating, planning, organizing, and administering medical and nursing care and services for patients. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Peak flow: The maximum amount of air breathed out; the power needed to produce this amount. [EU] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Pendulous: A condition in which the anterior part of the abdominal wall is so relaxed that it hangs down over the pubic region. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillin G: A penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on GABA mediated synaptic transmission. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH]
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Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] 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] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and
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peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phimosis: The inability to retract the foreskin over the glans penis due to tightness of the prepuce. [NIH]
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Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [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]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebo Effect: An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins
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that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Transfusion: The transfer of blood platelets from a donor to a recipient or reinfusion to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pneumococcal Infections: Infections with bacteria of the species Streptococcus pneumoniae. [NIH]
Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polyarthritis: An inflammation of several joints together. [EU] 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]
Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides,
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proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polymyalgia Rheumatica: A syndrome in the elderly characterized by proximal joint and muscle pain, high erythrocyte sedimentation rate, and a self-limiting course. Pain is usually accompanied by evidence of an inflammatory reaction. Women are affected twice as commonly as men and Caucasians more frequently than other groups. The condition is frequently associated with temporal arteritis and some theories pose the possibility that the two diseases arise from a single etiology or even that they are the same entity. [NIH] 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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Polyvinyl Alcohol: A polymer prepared from polyvinyl acetates by replacement of the acetate groups with hydroxyl groups. It is used as a pharmaceutic aid and ophthalmic lubricant as well as in the manufacture of surface coatings artificial sponges, cosmetics, and other products. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH]
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Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnenolone: Steroid hormone. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primum: The first atrial septum to appear in the embryonic heart. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block.
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(From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Proctitis: Inflammation of the rectum. [EU] Proctocolectomy: An operation to remove the colon and rectum. Also called coloproctectomy. [NIH] Proctosigmoiditis: Irritation of the rectum and the sigmoid colon. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [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] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propolis: Resinous substance obtained from beehives; contains many different substances which may have antimicrobial or antimycotic activity topically; its extracts are called propolis resin or balsam. Synonyms: bee bread; hive dross; bee glue. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond
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(5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] 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] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostaglandins, Synthetic: Compounds obtained by chemical synthesis that are analogs or derivatives of naturally occurring prostaglandins and that have similar activity. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] 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]
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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]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Sarcoidosis: A disease of unknown etiology characterized by tuberclelike, granulomatous nodules which may affect the skin, the lungs, the lymph nodes, the bones of the distal extremities, the conjunctiva, the lacrimal gland, the retina and the uveal tract. [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]
Pupil: The aperture in the iris through which light passes. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and
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interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] RANTES: A chemokine that is a chemoattractant for eosinophils, monocytes, and lymphocytes. It is a potent and selective eosinophil chemotaxin that is stored in and released from platelets and activated T-cells. [NIH] Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the trochlear nucleus in the midbrain to the hypoglossal area in the medulla oblongata. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reagin: The antibody-like substances responsible for allergic phenomena; part of the gamma globulin fraction of serum. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH]
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Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Refractometry: Measurement of the index of refraction (the ratio of the velocity of light or other radiation in the first of two media to its velocity in the second as it passes from one into the other). [NIH] Refractory: Not readily yielding to treatment. [EU] 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] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual Volume: The volume of air remaining in the lungs at the end of a maximal expiration. Common abbreviation is RV. [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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions.
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[NIH]
Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retraction: 1. The act of drawing back; the condition of being drawn back. 2. Distal movement of teeth, usually accomplished with an orthodontic appliance. [EU] Retrobulbar: Behind the pons. [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retroperitoneal Fibrosis: A slowly progressive condition of unknown etiology, characterized by deposition of fibrous tissue in the retroperitoneal space compressing the ureters, great vessels, bile duct, and other structures. When associated with abdominal aortic aneurysm, it may be called chronic periaortitis or inflammatory perianeurysmal fibrosis. [NIH]
Retroperitoneal Space: An area occupying the most posterior aspect of the abdominal cavity. It is bounded laterally by the borders of the quadratus lumborum muscles and extends from the diaphragm to the brim of the true pelvis, where it continues as the pelvic extraperitoneal space. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although
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infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Rubidium: An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells. [NIH] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to
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create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizophrenia, Catatonic: A type of schizophrenia characterized by abnormality of motor behavior which may involve particular forms of stupor, rigidity, excitement or inappropriate posture. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH]
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Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH]
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Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the
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brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] Space Flight: Travel beyond the earth's atmosphere. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] 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]
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Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphenoid Sinus: One of the paired paranasal sinuses, located in the body of the sphenoid bone and communicating with the highest meatus of the nasal cavity on the same side. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Sphincter of Oddi: The muscle between the common bile duct and pancreatic ducts. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [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] Splenectomy: An operation to remove the spleen. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Steady state: Dynamic equilibrium. [EU] Steatosis: Fatty degeneration. [EU]
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Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stool test: A test to check for hidden blood in the bowel movement. [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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subcapsular: Situated below a capsule. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
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[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] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superior Cervical Ganglion: The largest and uppermost of the paravertebral sympathetic ganglia. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the
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nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [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] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein
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synthesis. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with 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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH]
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Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU]
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Trabecular Meshwork: A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of
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management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triamcinolone Acetonide: An esterified form of triamcinolone. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions. [NIH]
Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trophic: Of or pertaining to nutrition. [EU] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor Lysis Syndrome: A syndrome resulting from cytotoxic therapy, occurring generally in aggressive, rapidly proliferating lymphoproliferative disorders. It is characterized by combinations of hyperuricemia, lactic acidosis, hyperkalemia, hyperphosphatemia and hypocalcemia. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of
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ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those ionophores that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in
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which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveal tract: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure and flow rate, as well as oxygen content, are increased. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving
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around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH]
Dictionary 335
Wart: A raised growth on the surface of the skin or other organ. [NIH] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [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] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zona Fasciculata: The wide middle zone of the adrenal cortex. This zone consists of large lipid-laden cells radially arranged in parallel cords. It converts pregnenolone to cortisol by a series of enzymatically regulated steps. A small amount of corticosterone is formed as a byproduct of cortisol synthesis. [NIH] Zona Glomerulosa: The narrow subcapsular outer zone of the adrenal cortex. This zone consists of granular cells which stain deeply and are arranged in rounded groups. It
336
Corticosteroids
converts pregnenolone to aldosterone by a series of enzymatically regulated steps. [NIH] Zona Reticularis: The inner zone of the adrenal cortex. This zone consists of an anastomosing network of cells which resemble those of the zona fasciculata except for the fact that they contain less lipid. The mitochondria are elongated and contain a mixture of tubular and flattened cristae. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
337
INDEX 6 6-Mercaptopurine, 219, 235 A Abdomen, 235, 247, 257, 286, 291, 305, 306, 318, 324, 325 Abdominal, 159, 162, 171, 173, 217, 218, 220, 235, 236, 287, 291, 303, 304, 305, 306, 318, 331 Abdominal fat, 159, 163, 235 Abdominal Pain, 217, 218, 220, 235, 287, 331 Aberrant, 80, 235 Ablate, 37, 235 Abscess, 172, 220, 235, 239, 321 Acantholysis, 235, 305 Acceptor, 235, 291, 303, 328, 330 Acetaminophen, 218, 235 Acetylcholine, 235, 253, 292, 300 Acetylcysteine, 119, 235 Acidosis, 219, 235, 331 Acitretin, 93, 235 Actin, 55, 235 Adaptability, 235, 251 Adaptation, 12, 45, 50, 236, 309 Adduct, 174, 236 Adenine, 236 Adenosine, 70, 236, 308, 328 Adipocytes, 236, 257, 289 Adipose Tissue, 235, 236 Adjunctive Therapy, 158, 236 Adjustment, 8, 51, 236 Adolescence, 19, 236 Adrenal Cortex, 148, 153, 164, 168, 170, 175, 236, 237, 258, 269, 280, 312, 335, 336 Adrenal Glands, 60, 143, 159, 168, 236 Adrenal insufficiency, 5, 70, 236 Adrenal Medulla, 236, 250, 268, 300 Adrenaline, 130, 236 Adrenergic, 13, 15, 16, 18, 42, 55, 236, 237, 241, 263, 268, 292, 326 Adrenergic beta-Antagonists, 236, 241 Adverse Effect, 6, 51, 56, 64, 104, 108, 155, 161, 236, 238, 264, 307, 322 Aerobic, 236, 296, 303, 314 Aerosol, 102, 236, 245, 326 Afferent, 237, 289, 302, 311 Affinity, 26, 58, 151, 237, 243, 291, 323 AFP, 220, 237
Agar, 237, 308 Age Groups, 19, 237 Aged, 80 and Over, 237 Agonist, 15, 16, 18, 28, 42, 94, 112, 180, 237, 263, 287, 298, 300, 327 Airway Obstruction, 36, 54, 63, 75, 83, 237 Albumin, 38, 154, 237, 303, 309 Albuterol, 15, 16, 18, 237 Aldosterone, 10, 61, 68, 237, 296, 336 Algorithms, 34, 237, 246 Alimentary, 6, 237, 304 Alkaline, 165, 235, 237, 239, 244, 248, 307, 327 Alkaloid, 238, 243, 254, 255, 297, 300, 304, 328 Alkylating Agents, 238, 252 Allergen, 23, 32, 36, 43, 48, 96, 99, 238, 262, 321 Allergic Rhinitis, 23, 67, 99, 106, 116, 131, 159, 238, 248, 261, 277 Allogeneic, 117, 238, 277 Allograft, 65, 94, 238 Allopurinol, 119, 238 Alopecia, 36, 238, 259 Alpha-1, 214, 238, 259 Alternative medicine, 194, 238 Amblyopia, 118, 238 Amebiasis, 238, 295 Ameliorated, 56, 180, 238 Ameliorating, 57, 238 Amenorrhea, 131, 154, 238, 240 Amino Acid Sequence, 168, 169, 238, 240, 245, 270 Amino Acids, 148, 154, 238, 240, 245, 269, 300, 305, 310, 313, 326, 330, 332 Aminoglutethimide, 182, 239 Aminoquinolines, 186, 239 Ammonia, 239, 276, 326 Amphetamine, 181, 239, 262 Ampulla, 239, 252 Amygdala, 18, 239, 244, 290 Anaesthesia, 76, 239, 283 Anal, 30, 218, 220, 239, 272 Anal Fistula, 218, 239 Analgesic, 51, 235, 239, 254, 263, 295, 297, 301 Analog, 239, 254, 272, 289, 301 Analogous, 163, 239, 264, 330
338
Corticosteroids
Analytes, 239, 326 Anatomical, 172, 239, 243, 252, 283, 296, 320 Androgenic, 239, 260 Androgens, 13, 21, 152, 236, 239, 242 Anemia, 219, 239, 273 Anesthesia, 22, 86, 110, 237, 239, 259, 266, 311 Anesthetics, 5, 93, 239, 268 Angioplasty, 72, 240 Angiotensin-Converting Enzyme Inhibitors, 240, 241 Angiotensinogen, 240, 317 Anhydrous, 176, 240 Animal model, 24, 30, 32, 36, 60, 64, 187, 240 Anions, 237, 240, 287 Anogenital, 240, 257 Anorexia, 51, 131, 154, 240, 332 Anorexia Nervosa, 131, 154, 240 Antagonism, 240, 328 Anterior chamber, 14, 240, 287, 330 Anthracyclines, 128, 240 Antiallergic, 240 Antibacterial, 240, 254, 323 Antibiotic, 158, 172, 179, 203, 240, 254, 260, 264, 269, 290, 299, 305, 323, 327 Antibodies, 44, 97, 146, 147, 153, 164, 186, 187, 240, 244, 277, 282, 297, 309 Antibody-Dependent Cell Cytotoxicity, 240, 288 Anticarcinogenic, 149, 241 Anticholinergic, 178, 179, 180, 219, 241 Anticoagulant, 241, 313 Anticonvulsant, 71, 124, 241, 249, 307 Antidepressant, 62, 241 Antifungal, 6, 35, 112, 241, 287, 288, 295, 322 Antigen, 31, 40, 48, 147, 237, 240, 241, 256, 279, 281, 282, 283, 284, 294, 296, 321, 326 Antigen-presenting cell, 31, 241 Antihistamine, 158, 172, 241 Antihypertensive, 196, 241 Antihypertensive Agents, 196, 241 Anti-infective, 180, 241, 252, 280 Anti-Inflammatory Agents, 8, 151, 169, 177, 178, 220, 241 Antimetabolite, 235, 241, 272, 295 Antimicrobial, 168, 169, 241, 253, 312 Antimycotic, 241, 312 Antineoplastic, 235, 238, 241, 246, 254, 259, 264, 272, 295, 322, 334
Antioxidant, 241, 243, 303 Antiproliferative, 148, 241 Antipyretic, 235, 241 Antispasmodic, 242, 301 Antithymocyte globulin, 39, 242 Antitussive, 196, 242, 301 Antiviral, 235, 242, 285 Anuria, 242, 288 Anus, 218, 239, 240, 242, 243, 244, 247, 255, 267, 286, 316 Anxiety, 236, 242, 252 Aortic Aneurysm, 242, 274, 318 Aplastic anemia, 40, 242 Apnea, 242 Apoptosis, 24, 47, 60, 124, 242, 250 Aqueous, 13, 146, 150, 161, 176, 180, 242, 245, 247, 253, 260, 266, 272, 280, 289, 291, 330 Aqueous humor, 14, 242, 247, 253, 330 Arachidonic Acid, 27, 32, 58, 166, 170, 242, 265, 290, 291, 312 Arginine, 18, 242, 279, 300 Aromatase, 239, 242 Arterial, 171, 242, 258, 281, 289, 313, 327 Arteries, 72, 242, 247, 258, 292, 298, 309, 315, 328 Arterioles, 242, 247, 249 Arteritis, 72, 78, 101, 111, 242, 310 Artery, 159, 240, 242, 258, 266, 305, 315, 327 Articular, 80, 92, 166, 242, 302, 331 Ascites, 187, 242 Ascorbic Acid, 123, 242 Aseptic, 157, 243, 325 Asparaginase, 128, 243 Aspartate, 243 Aspergillosis, 34, 84, 99, 243, 287 Aspergillus, 34, 105, 118, 243 Assay, 37, 52, 105, 153, 243, 282, 331 Astrocytes, 45, 243, 293, 296, 297 Asymptomatic, 189, 238, 243, 304 Atmospheric Pressure, 243, 280 Atopic, 68, 103, 109, 112, 127, 130, 155, 243 Atopic Eczema, 68, 103, 127, 243 Atresia, 19, 243, 245 Atrial, 243, 258, 311, 331 Atrioventricular, 82, 243, 258 Atrium, 243, 258, 331, 333 Atrophy, 235, 243, 291 Atropine, 219, 243, 245, 263 Attenuated, 55, 243, 263 Attenuation, 125, 243
339
Auditory, 243, 311 Autacoids, 243, 283, 284 Autoantibodies, 244, 261 Autodigestion, 244, 304 Autoimmune disease, 8, 64, 149, 157, 187, 195, 218, 244, 298, 309 Autoimmune Hepatitis, 4, 78, 244 Autoimmunity, 186, 244 Autologous, 39, 244 Autonomic Neuropathy, 60, 244 Autoradiography, 25, 62, 244 Axillary, 72, 244 B Bacterial Physiology, 236, 244 Bactericidal, 244, 269 Bacterium, 244, 251, 278 Bacteriuria, 244, 332 Barium, 217, 218, 244 Barium enema, 218, 244 Basal cell carcinoma, 37, 244 Basal cells, 244 Basal Ganglia, 244, 253, 274, 290 Basal Ganglia Diseases, 244, 253 Base, 22, 152, 164, 165, 236, 244, 245, 261, 273, 288, 307, 327, 331, 332 Basement Membrane, 26, 245, 270, 289 Basophils, 166, 245, 277 Beclomethasone, 163, 245 Bed Rest, 154, 245 Belladonna, 243, 245 Benign, 149, 156, 233, 245, 260, 274, 288, 299, 316, 320 Benign tumor, 156, 245 Beta-Endorphin, 25, 245 Bile, 49, 187, 189, 217, 245, 252, 273, 280, 287, 291, 311, 318, 325, 332 Bile Acids, 245, 325 Bile Acids and Salts, 245 Bile duct, 187, 245, 311, 318 Bile Pigments, 245, 287 Biliary, 19, 38, 189, 245, 249, 252, 255, 304 Biliary Atresia, 19, 245 Biliary Tract, 245, 249, 304 Bilirubin, 237, 245, 280 Binding Sites, 38, 147, 245 Biochemical, 30, 56, 61, 62, 173, 182, 189, 241, 245, 276, 288, 289, 302, 321 Biological response modifier, 246, 285 Biological therapy, 246, 277 Biomolecular, 246, 326 Biopsy, 4, 216, 218, 246, 306 Biosynthesis, 144, 242, 246, 313
Biotechnology, 65, 68, 194, 209, 246 Biotransformation, 246, 307 Biphasic, 50, 246 Bipolar Disorder, 66, 131, 246 Bladder, 244, 246, 256, 298, 313, 332 Blastocyst, 246, 257, 266, 308 Blastomycosis, 246, 287 Blasts, 39, 246 Bleomycin, 32, 246 Blepharitis, 40, 132, 246 Blinking, 162, 246 Blister, 246, 305 Bloating, 218, 220, 247, 287 Blood Coagulation, 247, 248, 328 Blood Glucose, 247, 278, 281, 285 Blood Platelets, 247, 309, 321 Blood vessel, 45, 52, 215, 247, 250, 252, 253, 258, 266, 267, 270, 275, 278, 287, 291, 292, 295, 306, 308, 323, 325, 328, 333 Blood-Aqueous Barrier, 247, 272 Blood-Brain Barrier, 44, 247 Blood-Retinal Barrier, 247, 272 Blot, 24, 25, 247 Body Composition, 73, 127, 247 Body Fluids, 247, 248, 264, 272, 301, 323 Body Mass Index, 171, 247 Bone Density, 7, 247 Bone Marrow, 40, 158, 242, 247, 259, 274, 277, 278, 282, 292, 293, 323, 325 Bone scan, 247, 319 Bowel Movement, 218, 247, 248, 325 Brachytherapy, 247, 285, 287, 315, 335 Bradykinin, 248, 300, 309 Bronchi, 248, 268, 328, 330 Bronchial, 24, 33, 49, 67, 69, 79, 107, 125, 166, 248, 279, 328 Bronchial Provocation Tests, 107, 248 Bronchitis, 30, 131, 248, 253 Bronchoalveolar Lavage, 48, 248 Bronchoconstriction, 31, 78, 180, 248 Bronchodilator, 20, 54, 248 Bronchopulmonary, 99, 100, 248 Bronchopulmonary Dysplasia, 100, 248 Bronchoscopy, 36, 248 Bronchospasm, 75, 248 Bronchus, 248 Buccal, 248, 281, 292 Budesonide, 31, 74, 101, 189, 191, 248 Buffers, 148, 248 Bulking Agents, 217, 248 Bullous, 74, 248, 261 Bupivacaine, 175, 248, 290
340
Corticosteroids
Bypass, 216, 248 C Calcium, 7, 9, 14, 120, 121, 241, 248, 249, 256, 294, 304, 322, 327 Calcium Channel Blockers, 14, 241, 249 Calcium Channels, 9, 249, 304 Calculi, 249, 276 Caloric intake, 219, 249 Candidiasis, 6, 249 Candidosis, 249 Cannabidiol, 249 Cannabinoids, 10, 14, 17, 249 Cannabinol, 249 Capillary, 61, 87, 247, 248, 249, 275, 333 Capsules, 11, 159, 166, 249, 275 Carbamazepine, 124, 249 Carbohydrate, 127, 152, 164, 170, 175, 249, 276, 310 Carbon Dioxide, 249, 272, 274, 308, 317 Carbonate Dehydratase, 249, 250 Carbonic Anhydrase Inhibitors, 14, 250 Carcinogen, 236, 250, 295, 298 Carcinogenesis, 36, 250 Carcinogenic, 238, 250, 284, 312, 325 Carcinoma, 37, 250, 259 Cardiac, 8, 29, 60, 74, 236, 250, 258, 265, 266, 268, 269, 290, 298, 325, 326 Cardiomyopathy, 60, 250 Cardiovascular, 8, 14, 61, 152, 157, 159, 171, 173, 175, 239, 244, 249, 250, 290, 321 Cardiovascular disease, 8, 14, 61, 159, 171, 173, 250 Cardiovascular System, 152, 175, 244, 250 Carotene, 250, 318 Carpal Tunnel Syndrome, 93, 132, 250 Carrier Proteins, 250, 309 Case report, 107, 128, 250 Caspase, 157, 250 Catalepsy, 17, 250 Cataract, 69, 109, 250 Catecholamine, 250, 263, 307 Catheter, 250, 266, 286 Catheterization, 240, 250, 286 Cat-Scratch Disease, 102, 251 Caudal, 251, 281, 310 Cause of Death, 29, 173, 251 Caustic, 251 Cecum, 251, 289 Celiac Disease, 132, 196, 251 Cell Cycle, 251, 259, 333 Cell Death, 24, 86, 242, 251, 299 Cell Differentiation, 11, 251, 322
Cell Division, 244, 251, 277, 296, 308 Cell Extracts, 53, 251 Cell membrane, 170, 249, 250, 251, 261, 286, 308 Cell proliferation, 251, 285, 322 Cell Size, 36, 251 Cell Survival, 61, 251, 277 Cerebral, 45, 106, 244, 247, 251, 252, 257, 268, 269, 272, 273, 304, 327, 328 Cerebral Cortex, 251, 269, 272 Cerebral Palsy, 106, 252 Cerebrovascular, 244, 249, 250, 252 Cerebrum, 251, 252 Cerumen, 153, 252 Cervical, 186, 252, 294 Cervix, 252 Character, 22, 252, 260, 276 Chemokines, 64, 252 Chemotactic Factors, 166, 252, 256 Chemotherapeutic agent, 160, 252 Chemotherapy, 61, 77, 149, 154, 252 Chenodeoxycholic Acid, 252, 332 Chin, 252, 295 Chiropractic, 129, 136, 252 Chloral Hydrate, 25, 252 Chlorambucil, 4, 72, 252 Chlorhexidine, 6, 252 Choleretic, 252, 332 Cholestasis, 19, 50, 187, 252 Cholesterol, 4, 82, 133, 153, 171, 245, 253, 258, 265, 280, 291, 292, 325, 327 Cholinergic, 9, 13, 253, 300 Cholinergic Agonists, 14, 253 Chondrocytes, 80, 253 Chorea, 109, 253 Choreatic Disorders, 253 Choroid, 253, 318, 333 Chromaffin System, 253, 267 Chromatin, 37, 242, 253, 293 Chromosomal, 80, 253, 279 Chromosome, 253, 277, 290 Chronic Disease, 27, 41, 158, 253, 255, 289 Chronic Fatigue Syndrome, 81, 132, 149, 253 Chronic Obstructive Pulmonary Disease, 20, 72, 77, 81, 89, 90, 92, 95, 108, 118, 132, 253 Ciliary, 14, 242, 247, 253, 297, 333 Ciliary processes, 242, 253 Ciprofloxacin, 66, 217, 253 Circadian, 66, 75, 116, 190, 253 Circadian Rhythm, 190, 253
341
Circulatory system, 253, 267 Circumcision, 178, 253 Cirrhosis, 187, 189, 254, 310, 311 CIS, 24, 254, 283, 318 Cladribine, 72, 254 Clamp, 10, 45, 254 Clarithromycin, 217, 254 Clindamycin, 186, 254 Clobetasol, 6, 254 Cloning, 187, 246, 254 Closing Volume, 48, 254 Coagulation, 247, 254, 278, 309 Coca, 254 Cocaine, 181, 254 Cochlea, 254, 284 Codeine, 219, 254, 301 Coenzyme, 243, 254, 288 Cognition, 21, 81, 254 Cohort Studies, 14, 255 Colchicine, 15, 16, 82, 187, 255 Colitis, 58, 135, 189, 190, 196, 214, 216, 217, 218, 219, 255, 287 Collagen, 245, 255, 270, 271, 280, 294, 309, 320 Collagen disease, 255, 280, 320 Collagenous Colitis, 27, 196, 255 Collapse, 164, 255, 323 Colloidal, 237, 255, 307, 326 Colon, 27, 58, 163, 191, 196, 197, 218, 220, 244, 255, 284, 287, 289, 312, 322, 331 Colonoscopy, 217, 255 Colorectal, 14, 255 Colorectal Cancer, 14, 255 Combination chemotherapy, 127, 255 Combination Therapy, 89, 187, 255 Common Bile Duct, 255, 324 Complement, 241, 255, 256, 274, 309, 321 Complementary and alternative medicine, 123, 141, 256 Complementary medicine, 123, 256 Complete remission, 256, 317 Complete response, 6, 53, 256 Compliance, 31, 89, 118, 256 Computational Biology, 209, 256 Computed tomography, 48, 247, 256, 319 Computerized axial tomography, 256, 319 Computerized tomography, 256 Conception, 257, 271, 294, 311, 325 Concomitant, 6, 62, 79, 257 Condylomata Acuminata, 150, 257 Cones, 257, 318 Congestion, 99, 135, 257, 260, 268
Conjugated, 46, 245, 252, 257, 260 Conjunctiva, 40, 257, 288, 315, 320 Conjunctivitis, 40, 132, 257, 277 Connective Tissue, 38, 148, 243, 247, 255, 257, 262, 271, 274, 292, 293, 295, 306, 318, 319, 327 Connective Tissue Cells, 257 Consciousness, 239, 257, 263, 314 Constipation, 257, 273, 287 Constriction, 180, 257, 287, 314, 335 Contact dermatitis, 117, 156, 157, 257 Contamination, 257, 278 Continent Ileostomy, 218, 257 Contraception, 152, 257 Contraindications, ii, 186, 257 Contrast Media, 257, 335 Contrast Sensitivity, 257, 302 Control group, 28, 33, 257 Controlled study, 42, 257 Convulsions, 231, 241, 257, 265 Coordination, 258, 298 Cor, 10, 17, 52, 53, 62, 153, 168, 170, 201, 258 Cornea, 36, 240, 242, 258, 288, 320, 333 Corneal Ulcer, 162, 258 Corneum, 258, 268 Coronary, 149, 159, 250, 258, 298 Coronary heart disease, 250, 258 Coronary Thrombosis, 258, 298 Corpus, 152, 258, 292, 305, 312, 321, 328, 334 Corpus Luteum, 152, 258, 292, 312 Cortex, 153, 238, 258, 267, 311 Cortical, 9, 11, 45, 57, 238, 258, 269, 311, 321 Corticotropin-Releasing Hormone, 17, 258 Cortisone, 67, 148, 170, 258, 262, 311 Cortodoxone, 170, 259 Cranial, 94, 126, 259, 269, 299, 302, 304, 306, 324 Creatine, 125, 259 Creatinine, 4, 259, 288, 332 Critical Care, 20, 81, 85, 86, 89, 90, 96, 107, 109, 110, 112, 113, 116, 119, 259 Croton Oil, 259, 308 Cryotherapy, 156, 259 Crystallization, 176, 259 Cultured cells, 24, 53, 259 Curare, 259, 298 Curative, 259, 328 Cutaneous, 132, 156, 169, 246, 249, 257, 259, 281, 287, 289, 290, 292
342
Corticosteroids
Cyclic, 14, 259, 277, 300, 308, 313, 328 Cyclin, 47, 259 Cyclodextrins, 117, 150, 259 Cyclophosphamide, 4, 5, 66, 72, 87, 101, 259 Cyclosporine, 39, 56, 64, 72, 190, 259, 283 Cyproterone, 259, 272 Cysteine, 138, 140, 235, 252, 259, 326 Cytochrome, 10, 242, 259 Cytokine, 11, 14, 30, 43, 58, 73, 80, 260, 285, 322 Cytomegalovirus, 46, 260 Cytopenia, 39, 260 Cytoplasm, 242, 245, 251, 260, 268, 293 Cytoprotection, 61, 260 Cytotoxic, 4, 12, 65, 95, 218, 260, 283, 285, 316, 322, 331 Cytotoxicity, 60, 260 D Danazol, 89, 95, 260 Daunorubicin, 260, 264 De novo, 94, 260 Decidua, 260, 308 Decongestant, 158, 172, 260 Degenerative, 260, 278, 293, 302 Dehydration, 163, 165, 260 Dehydroepiandrosterone, 21, 28, 127, 138, 260 Deletion, 38, 242, 260 Demography, 187, 260 Dendrites, 260, 261, 299 Dental Caries, 261, 272 Dentate Gyrus, 261, 279 Dentures, 261, 335 Deoxyribonucleic, 156, 261, 319 Deoxyribonucleic acid, 156, 261, 319 Deoxyribonucleotides, 261 Depigmentation, 261, 334 Depolarization, 261, 322 Depressive Disorder, 21, 261, 291 Deprivation, 238, 261 Dermatitis, 70, 109, 112, 130, 132, 135, 155, 161, 261, 265, 286 Dermatitis Herpetiformis, 156, 261 Dermatitis, Atopic, 161, 261 Dermatitis, Contact, 161, 261 Dermatology, 36, 52, 71, 72, 74, 75, 85, 87, 92, 93, 100, 101, 111, 112, 117, 261 Dermatosis, 160, 161, 261 Dermis, 262, 318, 326, 330 Desensitization, 262, 283 Desiccation, 162, 262
Desonide, 170, 262 Desoximetasone, 170, 262 Detoxification, 181, 262 Deuterium, 262, 280 Developmental Biology, 57, 262 Dexamethasone, 30, 128, 155, 167, 170, 175, 179, 182, 201, 203, 262 Dextroamphetamine, 239, 262 Diabetes Mellitus, 70, 85, 126, 149, 159, 163, 171, 216, 262, 275, 278, 301, 305 Diabetic Retinopathy, 262, 308 Diagnostic procedure, 145, 195, 262 Diarrhea, 50, 196, 217, 218, 220, 238, 262, 273, 287 Diarrhoea, 262, 281 Diastole, 262 Diastolic, 163, 262, 281 Diffusion, 262, 263, 284, 286 Digestion, 237, 245, 247, 262, 286, 291, 304, 325 Digestive tract, 218, 244, 262, 323, 324 Digitalis, 262, 303 Dihydrotestosterone, 263, 317 Dihydroxy, 163, 165, 237, 263, 269 Dilated cardiomyopathy, 60, 263 Dilution, 104, 146, 263, 309 Dimerization, 59, 263 Dimethyl, 263, 292 Diphenoxylate, 219, 263 Diploid, 263, 308 Direct, iii, 20, 25, 37, 51, 199, 263, 275, 304, 317, 327 Discoid, 218, 263 Discrete, 263, 290 Disinfectant, 252, 263, 269 Disposition, 261, 263 Dissociation, 237, 263 Distal, 47, 191, 263, 265, 314, 315, 318 Diuresis, 263, 328 Diuretics, Thiazide, 241, 263 Diurnal, 172, 263 Dizziness, 155, 263, 334 Dopamine, 239, 254, 262, 263, 297, 300, 307 Dorsal, 264, 268, 310 Dose-dependent, 80, 157, 264 Double-blind, 48, 54, 58, 61, 264 Double-blinded, 48, 264 Doxorubicin, 60, 72, 264 Drive, ii, vi, 4, 11, 24, 32, 50, 115, 185, 218, 264, 287, 290 Dross, 264, 312 Drug Design, 45, 264
343
Drug Interactions, 203, 204, 264 Drug Resistance, 35, 264 Drug Tolerance, 264, 329 Drug Toxicity, 250, 264 Dry Eye Syndrome, 162, 264 Duct, 45, 239, 250, 255, 264, 270, 293, 319, 326 Duodenal Ulcer, 166, 264 Duodenum, 245, 264, 300, 304, 325 Dura mater, 265, 294, 303 Dyes, 245, 265, 326 Dyslipidemia, 171, 265 Dyspnea, 29, 78, 180, 265, 315 Dystrophy, 124, 265 E Ear Diseases, 152, 265 Eating Disorders, 10, 265 Eczema, 132, 133, 155, 261, 265 Edema, 5, 53, 196, 257, 262, 265, 298, 299, 332 Effector, 46, 235, 240, 255, 265, 288, 308 Effector cell, 240, 265, 288 Effusion, 158, 265 Eicosanoids, 27, 32, 58, 265 Elastic, 265, 276, 326 Elastin, 255, 265, 270 Electroconvulsive Therapy, 182, 265 Electrode, 14, 265 Electrolyte, 152, 175, 237, 265, 272, 288, 296, 301, 310, 323, 332 Electrons, 241, 245, 265, 287, 303, 315, 316, 326 Embolism, 82, 266 Embolus, 266, 284 Embryo, 246, 251, 266, 283, 311, 324 Embryo Transfer, 266, 311 Embryology, 38, 266 Emesis, 77, 232, 266 Emphysema, 133, 253, 266 Emulsion, 154, 155, 244, 266, 272 Encapsulated, 31, 266 Encephalitis, 86, 266 Encephalitis, Viral, 266 Endarterectomy, 240, 266 Endemic, 266, 324 Endocarditis, 76, 133, 249, 266 Endocardium, 266 Endocrine Glands, 266, 267, 304 Endocrine System, 175, 267, 299 Endogenous, 17, 21, 25, 26, 57, 151, 168, 169, 182, 190, 245, 263, 265, 267, 284, 330 Endometriosis, 260, 267
Endometrium, 152, 260, 267, 294 Endorphins, 267, 300 Endoscopy, 218, 267 Endothelial cell, 53, 60, 247, 266, 267, 328 Endothelium, 146, 267, 300 Endothelium, Lymphatic, 267 Endothelium, Vascular, 267 Endothelium-derived, 267, 300 Endotoxin, 32, 267, 331 Endotracheal intubation, 180, 267 Enema, 267 Energy balance, 267, 289 Enhancer, 151, 267, 317 Enkephalin, 245, 267 Enterocolitis, 99, 267 Enterocytes, 50, 267 Entorhinal Cortex, 267, 279 Environmental Health, 208, 210, 267 Enzymatic, 32, 144, 249, 250, 256, 261, 268, 279, 318 Enzyme Induction, 57, 268 Enzyme Inhibitors, 268, 309 Eosinophil, 31, 32, 66, 268, 316 Eosinophilia, 99, 268, 270 Eosinophilic, 30, 67, 75, 268, 270 Epidemic, 268, 324 Epidemiological, 15, 18, 73, 268 Epidermal, 34, 37, 268, 290 Epidermis, 36, 149, 156, 235, 244, 246, 258, 262, 268, 279, 290, 305, 315 Epidermoid carcinoma, 268, 324 Epinephrine, 68, 236, 263, 268, 300, 331 Episcleritis, 40, 268, 320 Epithelial Cells, 24, 58, 125, 162, 268, 289, 296 Epithelium, 23, 26, 36, 38, 124, 146, 152, 245, 247, 267, 268, 287 Erectile, 268, 305 Erection, 220, 268, 283 Erythema, 87, 133, 257, 268, 286, 332 Erythema Multiforme, 87, 268 Erythrina, 139, 140, 268 Erythrocytes, 66, 239, 247, 249, 269, 304, 317, 321 Erythromycin, 254, 269 Escalation, 28, 269 Esophageal, 110, 269 Esophagus, 243, 262, 269, 325 Estradiol, 68, 154, 269 Estrogen, 9, 59, 61, 152, 162, 239, 242, 259, 269, 312, 321, 327 Estrogen receptor, 59, 269
344
Corticosteroids
Ethanol, 11, 46, 269 Ethmoid, 172, 269, 304 Ethylene Glycol, 146, 269 Etretinate, 235, 269 Eukaryotic Cells, 269, 283 Evoke, 58, 269, 325 Excipient, 151, 178, 269 Excitability, 21, 269 Excitation, 269, 300 Excitatory, 10, 21, 269, 276, 287 Excitatory Amino Acid Agonists, 269, 287 Excrete, 242, 270, 288, 317 Exocrine, 270, 303, 304 Exogenous, 37, 81, 117, 166, 182, 246, 265, 267, 270, 284 Exon, 9, 68, 270 Expert Systems, 270, 273 Expiration, 270, 317 Expiratory, 18, 270 Extensor, 270, 314, 334 External-beam radiation, 270, 287, 315, 335 Extracellular, 14, 25, 45, 60, 243, 257, 270, 271, 294, 323, 327 Extracellular Matrix, 14, 45, 60, 257, 270, 271, 294 Extracellular Matrix Proteins, 60, 270, 294 Extracellular Space, 270 Extraction, 153, 270 Extremity, 72, 270, 289, 294, 304 Exudate, 270, 301 F Facial, 172, 270, 305 Family Planning, 209, 270 Fasciitis, 101, 270 Fatigue, 51, 99, 187, 253, 271, 278 Fatty acids, 126, 153, 237, 265, 271, 291, 312 Fatty Liver, 216, 271 Febrile, 56, 66, 271, 324 Feces, 257, 271, 325 Feeding Behavior, 17, 271 Femoral, 72, 154, 271, 279 Femoral Neck Fractures, 154, 271, 279 Femur, 271, 279 Fertilization in Vitro, 271, 311 Fetoprotein, 237, 271 Fetus, 26, 237, 271, 282, 293, 308, 311, 324, 325, 333 Fibrin, 47, 60, 247, 271, 328 Fibrinogen, 271, 309, 328 Fibroblasts, 32, 257, 271
Fibronectin, 60, 271 Fibrosarcoma, 271 Fibrosis, 11, 23, 24, 32, 47, 98, 101, 117, 187, 271, 315, 318, 319, 320 Fibrotic tissue, 47, 271 Filtration, 55, 271, 288 Fissure, 220, 261, 272, 311 Fistula, 272, 301 Fixation, 272, 321 Flexor, 270, 272, 290 Fludarabine, 72, 272 Fluid Therapy, 272, 301 Flumethasone, 170, 176, 272 Fluocinonide, 6, 170, 254, 272 Fluorescence, 44, 84, 272 Fluorine, 176, 272 Fluorophotometry, 14, 272 Fluorouracil, 156, 272, 290 Fluprednisolone, 170, 272 Flushing, 155, 272 Flutamide, 13, 272 Folate, 186, 272, 273 Fold, 8, 164, 272, 273, 286, 303, 311 Folic Acid, 272, 273 Follow-Up Studies, 181, 273 Forearm, 247, 271, 273, 294 Fractionation, 44, 273 Frameshift, 273, 331 Frameshift Mutation, 273, 331 Free Radicals, 44, 241, 263, 273 Friction, 273, 286, 292 Frontal Lobe, 21, 273, 311 Fumigation, 273 Functional Disorders, 166, 273 Fungicide, 172, 273 Fungus, 249, 273 Fuzzy Logic, 172, 273 G Gallbladder, 235, 245, 273 Ganglia, 235, 244, 274, 299, 306, 326 Ganglion, 274, 302 Ganglionectomy, 14, 274 Ganglionic Blockers, 241, 274 Gas, 239, 249, 262, 272, 273, 274, 280, 287, 298, 300, 317, 326, 333 Gas exchange, 274, 317, 333 Gastric, 118, 127, 166, 244, 274, 279 Gastrin, 274, 279 Gastrointestinal, 27, 57, 128, 157, 190, 196, 217, 244, 248, 253, 268, 269, 274, 290, 321, 325
345
Gastrointestinal tract, 57, 190, 244, 269, 274, 290, 321 Gemtuzumab ozogamicin, 91, 274 Gene, 12, 13, 17, 18, 25, 26, 27, 36, 37, 38, 42, 45, 46, 50, 58, 59, 61, 66, 68, 94, 111, 242, 246, 268, 274, 280, 309, 317 Gene Expression, 17, 25, 26, 27, 36, 37, 46, 50, 58, 59, 274 Gene Therapy, 12, 94, 111, 274 General practitioner, 99, 274 Genetic Engineering, 246, 254, 274 Genetics, 18, 274, 307 Genital, 150, 215, 244, 253, 275, 286 Genomics, 19, 61, 275 Genotype, 15, 16, 63, 275, 307 Geriatric, 24, 275 Germ Cells, 275, 303, 327 Gestation, 26, 67, 275, 306, 308, 324 Giardiasis, 275, 295 Ginseng, 126, 138, 140, 275 Glomerular, 50, 56, 126, 219, 275, 286, 288 Glomerular Filtration Rate, 219, 275, 288 Glomeruli, 55, 216, 275 Glomerulosclerosis, 50, 275 Glomerulus, 275 Glucans, 259, 275 Glucaric Acid, 125, 275 Glucose, 34, 35, 148, 162, 171, 242, 247, 259, 262, 275, 276, 278, 285, 319, 332 Glucose Intolerance, 171, 262, 275 Glucose tolerance, 171, 275 Glucose Tolerance Test, 275, 276 Glutamate, 10, 39, 276, 307 Glutamic Acid, 273, 276, 300 Glutamine, 66, 276 Glutathione Peroxidase, 276, 321 Gluten, 196, 251, 276 Glycine, 18, 245, 252, 276, 300 Glycogen, 57, 276 Glycoprotein, 151, 271, 276, 289, 297, 328, 331 Glycosaminoglycans, 270, 276 Glycoside, 276, 302, 319 Glycosidic, 240, 276 Glycosylation, 67, 151, 276 Goblet Cells, 36, 267, 276 Gonad, 276 Gonadal, 11, 276, 325 Gout, 133, 149, 255, 276 Governing Board, 277, 311 Graft, 40, 65, 158, 160, 187, 242, 277, 283 Graft Rejection, 277, 283
Grafting, 277, 283 Graft-versus-host disease, 158, 242, 277 Gram-negative, 251, 277, 305, 314, 318 Gram-positive, 277, 305 Gram-Positive Bacteria, 277, 305 Granulocyte, 40, 277 Gravis, 98, 277 Growth factors, 27, 32, 34, 38, 57, 60, 277, 296 Guanylate Cyclase, 277, 300 H Habitual, 252, 277 Haematemesis, 266, 277 Hair follicles, 262, 277, 334 Half-Life, 151, 235, 277 Haploid, 277, 308 Haptens, 164, 237, 277 Hay Fever, 133, 238, 277 Health Behavior, 129, 277 Health Status, 5, 277, 278 Heart attack, 250, 278 Heart failure, 61, 240, 278, 315 Heartbeat, 278, 326 Hematologic malignancies, 14, 278 Hematology, 29, 87, 117, 278 Hematopoiesis, 40, 278 Hemodialysis, 278, 288 Hemodynamics, 49, 278 Hemoglobin, 219, 239, 269, 278, 289, 303 Hemoglobinopathies, 274, 278 Hemolytic, 270, 278 Hemorrhage, 262, 278, 315, 325 Hemostasis, 278, 321 Hepatic, 35, 38, 187, 237, 255, 276, 278, 291 Hepatitis, 3, 4, 19, 73, 75, 78, 100, 107, 133, 278 Hepatitis A, 4, 19, 278 Hepatocyte, 35, 38, 252, 278 Hepatovirus, 278 Hereditary, 253, 261, 276, 278, 306 Heredity, 274, 275, 279 Herpes, 34, 53, 86, 149, 279 Herpes Zoster, 279 Heterogeneity, 237, 279 Hip Fractures, 271, 279 Hippocampus, 9, 18, 21, 24, 26, 39, 56, 62, 261, 279, 290, 325 Hirsutism, 157, 259, 279, 281 Histamine, 80, 241, 248, 279, 292 Histology, 38, 279, 293 Histones, 253, 279 Homeostasis, 11, 23, 35, 36, 49, 50, 57, 279
346
Corticosteroids
Homologous, 259, 274, 279, 321, 327 Hormonal, 51, 59, 152, 177, 178, 243, 279 Horny layer, 268, 279 Horseradish Peroxidase, 164, 279 Hospital Mortality, 91, 279 Human growth hormone, 162, 279 Human papillomavirus, 257, 280 Humoral, 149, 277, 280 Humour, 280 Hybrid, 56, 280 Hybridization, 53, 280 Hydration, 174, 249, 280 Hydrocortisone, 148, 149, 170, 174, 191, 200, 203, 280 Hydrogen, 82, 173, 176, 235, 245, 248, 249, 262, 270, 276, 280, 291, 297, 300, 301, 303, 307, 314, 335 Hydrogen Peroxide, 82, 276, 280, 291 Hydrolysis, 246, 280, 287, 308, 310, 314 Hydrophilic, 154, 280 Hydroxides, 280 Hyperaemia, 257, 280 Hyperaldosteronism, 164, 280 Hyperbaric, 99, 280 Hyperbaric oxygen, 99, 280 Hyperbilirubinemia, 280, 287 Hypercholesterolemia, 50, 133, 265, 280 Hyperemesis, 69, 280 Hypericum, 125, 129, 280 Hyperkeratosis, 150, 281 Hyperlipidemia, 7, 265, 281 Hyperplasia, 36, 57, 164, 281, 290 Hypersecretion, 36, 281 Hypersensitivity, 8, 71, 88, 96, 131, 238, 262, 268, 281, 290, 319, 321 Hypertension, 4, 7, 157, 162, 171, 187, 219, 236, 240, 241, 249, 250, 281, 301, 310, 329, 332 Hyperthermia, 56, 281 Hypertrichosis, 279, 281 Hypertriglyceridemia, 265, 281 Hypertrophy, 8, 36, 258, 281, 290, 331 Hyperuricemia, 276, 281, 331 Hypesthesia, 281, 299 Hypnotic, 252, 281 Hypoglycemia, 175, 281 Hypoglycemic, 34, 281 Hypogonadism, 7, 281 Hypophyseal, 34, 281 Hypotension, 258, 274, 281, 300 Hypothalamic, 10, 11, 17, 21, 46, 57, 62, 89, 153, 172, 281
Hypothalamus, 10, 18, 62, 157, 168, 258, 267, 281, 290, 300, 308, 328 Hypoxia, 49, 175, 281 Hypoxic, 282, 295 I Idiopathic, 32, 50, 62, 89, 105, 154, 282, 319 Ileal, 50, 282 Ileitis, 50, 282 Ileostomy, 218, 282 Ileum, 50, 220, 251, 282, 300 Imidazole, 163, 279, 282, 295 Immortal, 81, 282 Immune Complex Diseases, 282, 309 Immune Sera, 282 Immune system, 4, 8, 18, 34, 149, 164, 175, 186, 215, 241, 244, 246, 265, 282, 283, 290, 293, 298, 333, 335 Immune Tolerance, 4, 282 Immunity, 34, 46, 60, 148, 149, 169, 282, 285, 330 Immunization, 153, 282, 283, 321 Immunoassay, 153, 282 Immunodeficiency, 12, 91, 282 Immunogen, 153, 282 Immunoglobulins, 282, 309 Immunohistochemistry, 11, 14, 45, 59, 60, 282 Immunologic, 19, 47, 157, 252, 282, 316 Immunophilins, 283, 322 Immunosuppressant, 187, 235, 238, 272, 283, 295, 322 Immunosuppression, 12, 30, 60, 190, 283, 293 Immunosuppressive, 4, 14, 39, 60, 100, 148, 160, 196, 215, 218, 259, 275, 283, 320, 327 Immunosuppressive Agents, 40, 100, 218, 283, 320 Immunosuppressive therapy, 283 Immunotherapy, 112, 246, 262, 283 Impairment, 21, 60, 70, 252, 283, 286, 293, 295 Implant radiation, 283, 285, 287, 315, 335 Implantation, 59, 257, 283 Impotent, 64, 283 In situ, 25, 27, 36, 53, 60, 62, 283 In Situ Hybridization, 25, 27, 36, 60, 62, 283 Incision, 283, 286 Indomethacin, 40, 128, 283 Induction, 3, 5, 9, 19, 23, 24, 27, 55, 57, 66, 67, 128, 239, 274, 283, 285, 312
347
Induction therapy, 128, 283 Infancy, 19, 284 Infant, Newborn, 237, 284 Infantile, 155, 261, 284, 291 Infarction, 14, 163, 284, 309 Infiltration, 166, 216, 284, 311 Inflammation Mediators, 166, 284 Inflammatory bowel disease, 7, 158, 189, 190, 197, 216, 217, 218, 219, 284 Infusion, 28, 91, 154, 155, 166, 284, 295, 330 Ingestion, 126, 175, 276, 281, 284, 309, 327 Inhalation, 27, 101, 200, 201, 202, 236, 248, 284, 309 Initiation, 8, 19, 24, 29, 284, 312, 330 Initiator, 284, 285 Inner ear, 63, 284 Innervation, 14, 284, 294 Inorganic, 280, 284, 298, 326 Insight, 19, 40, 47, 49, 284 Insomnia, 252, 284 Insulator, 284, 298 Insulin, 34, 57, 91, 126, 159, 162, 171, 173, 276, 284, 285, 319 Insulin-dependent diabetes mellitus, 171, 285 Insulin-like, 57, 126, 285 Intensive Care, 118, 158, 180, 285 Interferon, 12, 65, 66, 78, 91, 126, 157, 285 Interferon-alpha, 285 Interleukin-1, 11, 65, 157, 285 Interleukin-12, 157, 285 Interleukin-15, 65, 285 Interleukin-18, 11, 285 Interleukin-2, 285 Interleukins, 283, 285 Intermittent, 18, 54, 148, 264, 272, 285 Internal Medicine, 12, 16, 26, 49, 70, 88, 90, 91, 95, 116, 117, 278, 285 Internal radiation, 285, 287, 315, 335 Interstitial, 101, 247, 270, 285, 286, 287, 335 Intertrigo, 156, 286 Intestinal, 26, 49, 196, 216, 217, 220, 250, 251, 252, 267, 276, 286, 293, 304 Intestinal Mucosa, 251, 267, 286 Intestinal Obstruction, 217, 286 Intestine, 50, 166, 191, 217, 220, 245, 247, 255, 286, 289, 295 Intoxication, 286, 335 Intracellular, 25, 249, 284, 286, 300, 310, 313, 316, 321, 322 Intracranial Hypotension, 107, 286 Intramuscular, 166, 190, 286, 304, 331
Intramuscular injection, 166, 286 Intraocular, 167, 176, 286 Intraocular pressure, 167, 176, 286 Intravenous, 22, 28, 71, 80, 91, 155, 190, 216, 284, 286, 295, 304 Intrinsic, 37, 155, 237, 245, 286 Intubation, 75, 251, 286 Inulin, 275, 286 Invasive, 5, 34, 48, 149, 282, 286, 293, 303 Invertebrates, 169, 286 Involuntary, 244, 246, 253, 286, 298 Involution, 156, 286 Ion Channels, 243, 286, 307, 327 Ion Transport, 286, 296 Ionizing, 287, 294, 316 Ionophores, 14, 287, 332 Ions, 245, 248, 249, 250, 263, 265, 280, 286, 287 Iris, 240, 258, 287, 315, 333 Irradiation, 149, 287, 335 Irritable Bowel Syndrome, 273, 287 Irritants, 162, 287 Ischemia, 175, 243, 287 Itraconazole, 77, 287 J Jaundice, 189, 280, 287, 299 K Kainic Acid, 56, 287 Kb, 208, 288 Keratitis, 53, 161, 288 Keratoacanthoma, 156, 288 Keratoconjunctivitis, 107, 288, 322 Keratoconjunctivitis Sicca, 288, 322 Keto, 151, 152, 164, 165, 288 Ketoconazole, 159, 162, 163, 288 Ketosteroids, 176, 288 Kidney Disease, 55, 186, 208, 215, 219, 288 Kidney Failure, 50, 275, 288 Kidney Failure, Acute, 288 Kidney Failure, Chronic, 288 Killer Cells, 46, 288 Kinetic, 34, 287, 288 L Labyrinth, 254, 284, 288, 321, 334 Lacrimal, 64, 162, 288, 315, 322 Lacrimal gland, 64, 162, 288, 315 Lactate Dehydrogenase, 60, 288 Lactation, 152, 289, 303, 312 Laminin, 245, 270, 289 Lamivudine, 75, 107, 289 Large Intestine, 196, 220, 251, 255, 262, 286, 289, 316, 323
348
Corticosteroids
Laryngeal, 196, 289 Larynx, 289, 330 Latent, 44, 181, 289, 311 Lectins, 268, 289 Leg Ulcer, 82, 289 Leishmaniasis, 289, 305 Lens, 242, 250, 289, 334 Leprosy, 70, 289 Leptin, 51, 289 Lesion, 246, 288, 289, 291, 331 Leucine, 245, 289 Leucocyte, 238, 268, 289 Leukaemia, 128, 289 Leukemia, 34, 72, 116, 235, 254, 264, 274, 278, 290 Leukotrienes, 32, 126, 242, 265, 290, 291 Levamisole, 5, 290 Libido, 21, 239, 290 Lichen Planus, 6, 157, 161, 195, 269, 290 Lichenification, 261, 290 Lidocaine, 152, 290 Life cycle, 246, 290 Ligament, 290, 313 Ligands, 13, 48, 58, 290, 326 Ligation, 47, 290 Limbic, 62, 239, 290, 311 Limbic System, 239, 290, 311 Lincomycin, 254, 290 Linkage, 61, 240, 290, 305 Lip, 185, 291 Lipid, 10, 31, 58, 126, 162, 164, 175, 285, 287, 288, 291, 298, 303, 331, 335, 336 Lipid Peroxidation, 291, 303 Lipid Peroxides, 126, 291 Lipodystrophy, 116, 291 Lipophilic, 58, 154, 291 Lipopolysaccharide, 45, 48, 277, 291 Lipoprotein, 265, 277, 291, 292 Liposome, 31, 291 Lipoxygenase Inhibitors, 219, 291 Lithium, 164, 291 Liver cancer, 38, 237, 291 Liver Regeneration, 38, 291 Liver scan, 291, 319 Liver Transplantation, 4, 19, 116, 291 Lobe, 279, 291, 334 Local therapy, 190, 291 Localization, 44, 45, 282, 291 Locomotion, 292, 308 Long-Term Potentiation, 9, 292 Loperamide, 219, 292 Low-density lipoprotein, 265, 291, 292
Lubricants, 292 Lubrication, 64, 292 Luciferase, 13, 50, 292 Lung Transplantation, 74, 292 Lung volume, 254, 292 Lupus, 95, 134, 135, 186, 214, 218, 292, 327 Luteal Phase, 152, 292 Lutein Cells, 292, 312 Lymph, 186, 244, 252, 253, 267, 280, 292, 315, 317, 319 Lymph node, 186, 244, 252, 292, 315, 317, 319 Lymphatic, 116, 148, 149, 267, 284, 292, 295, 323, 324, 328, 329 Lymphatic system, 292, 323, 324, 328, 329 Lymphoblastic, 128, 292 Lymphocyte Depletion, 283, 293 Lymphocytic, 5, 72, 196, 293 Lymphoid, 46, 240, 289, 293 Lymphoma, 278, 292, 293 Lymphopenia, 166, 293 Lymphoproliferative, 254, 293, 331 M Maceration, 286, 293 Macroglia, 293, 296 Macrophage, 11, 32, 40, 48, 241, 285, 293 Magnetic Resonance Imaging, 107, 293, 319 Maintenance therapy, 54, 293 Malabsorption, 251, 293 Malignant, 87, 144, 241, 271, 291, 293, 299, 316, 319 Malignant tumor, 87, 293 Malnutrition, 7, 60, 196, 237, 243, 293 Mammary, 152, 293, 327 Manic, 246, 291, 293 Manifest, 51, 158, 182, 293 Marijuana Abuse, 17, 293 Mass Media, 155, 293 Maternal Deprivation, 62, 293 Maternal Exposure, 73, 294 Matrix metalloproteinase, 34, 44, 64, 96, 294 Maxillary, 172, 294, 304 Meat, 127, 294 Mechanical ventilation, 180, 248, 294 Medial, 269, 294, 302, 324 Median Nerve, 250, 294 Mediate, 9, 27, 45, 59, 148, 149, 263, 284, 288, 294 Mediator, 8, 17, 80, 285, 294, 321 Medical Staff, 264, 294
349
Medicament, 181, 182, 294 MEDLINE, 5, 209, 294 Melanin, 261, 287, 294, 307, 331 Memory, 21, 24, 39, 56, 82, 113, 240, 292, 294 Meninges, 251, 265, 294 Meningitis, 45, 69, 76, 110, 134, 287, 294 Menopause, 294, 310 Menstrual Cycle, 152, 292, 294, 312 Menstruation, 152, 238, 260, 292, 294 Mental, iv, 7, 12, 208, 210, 252, 254, 263, 271, 294, 295, 314, 320, 332 Mental Disorders, 295, 314 Mental Health, iv, 7, 12, 208, 210, 295, 314 Meperidine, 263, 295 Mercaptopurine, 190, 217, 295 Mesenchymal, 32, 47, 295 Meta-Analysis, 73, 79, 90, 95, 98, 295 Metabolic Clearance Rate, 151, 295 Metabolic disorder, 276, 295 Metabolite, 35, 235, 246, 263, 295, 312 Metaplasia, 64, 162, 295 Metastasis, 294, 295 Metastatic, 13, 295 Methotrexate, 14, 78, 102, 187, 190, 217, 219, 295 Methylprednisolone, 63, 170, 189, 295 Metronidazole, 217, 219, 295 Miconazole, 6, 295 Microbe, 295, 329 Microbiology, 236, 244, 296 Microglia, 45, 243, 296, 297 Microorganism, 296, 305, 334 Microscopy, 14, 40, 44, 57, 245, 279, 296 Migration, 11, 40, 60, 166, 296 Milliliter, 247, 296 Mineralocorticoid, 26, 62, 296 Mitochondria, 296, 336 Mitochondrial Swelling, 296, 299 Mitosis, 242, 289, 296 Mitosporic Fungi, 243, 296 Mobility, 80, 296 Mobilization, 149, 296 Modeling, 104, 264, 296 Modification, 274, 296, 315, 335 Molecular, 9, 24, 34, 45, 47, 48, 49, 50, 57, 59, 60, 61, 62, 97, 104, 124, 126, 146, 147, 187, 209, 211, 246, 249, 256, 261, 264, 271, 291, 297, 312, 316, 329, 331 Monitor, 29, 34, 108, 186, 218, 259, 297, 301 Monoamine, 182, 239, 262, 297
Monoclonal, 147, 153, 157, 160, 274, 287, 297, 315, 335 Monoclonal antibodies, 147, 153, 274, 297 Monocyte, 67, 100, 241, 297 Mononuclear, 271, 297, 331 Monophosphate, 70, 297 Monotherapy, 55, 94, 178, 179, 189, 297 Mood Disorders, 39, 297 Morphine, 254, 263, 264, 295, 297, 301 Morphological, 74, 166, 266, 273, 297 Morphology, 56, 60, 195, 250, 278, 297 Motility, 30, 81, 273, 283, 297, 321 Motion Sickness, 297, 299 Motor Activity, 9, 257, 297 Motor nerve, 297, 298 Mucins, 267, 276, 297, 319 Mucociliary, 297, 322 Mucocutaneous, 87, 289, 297 Mucolytic, 196, 235, 248, 297 Mucosa, 24, 158, 195, 292, 297, 298, 312 Mucositis, 297, 328 Mucus, 30, 36, 162, 172, 297, 298, 331 Multiple sclerosis, 34, 43, 45, 74, 97, 298, 302 Muscle relaxant, 98, 298, 307 Muscle Relaxation, 129, 298 Muscle tension, 298 Musculoskeletal System, 118, 298 Mustard Gas, 287, 298 Mutagenesis, 44, 298 Mutagens, 273, 298 Myelin, 298 Myocardial infarction, 7, 8, 14, 162, 258, 298 Myocardium, 8, 298 Myopathy, 157, 298 Myositis, 102, 298 Myxedema, 86, 298 N Naloxone, 245, 298 Nasal Cavity, 298, 304, 324 Natural killer cells, 46, 285, 298 Nausea, 77, 155, 157, 218, 298, 314, 332 NCI, 1, 207, 254, 299 Nebulizer, 146, 299 Necrosis, 12, 72, 156, 157, 242, 258, 270, 284, 298, 299, 319 Neomycin, 180, 200, 203, 299 Neonatal, 19, 79, 100, 103, 105, 118, 299 Neonatal Hepatitis, 19, 299 Neoplasia, 38, 269, 299 Neoplasm, 156, 299, 319, 331
350
Corticosteroids
Nephropathy, 4, 288, 299 Nephrosis, 56, 299 Nephrotic, 5, 50, 55, 72, 215, 216, 299 Nephrotic Syndrome, 5, 50, 72, 215, 216, 299 Nervous System, 117, 118, 152, 157, 175, 235, 237, 239, 240, 245, 249, 250, 251, 254, 262, 274, 276, 290, 292, 294, 296, 297, 298, 299, 300, 302, 305, 306, 307, 321, 326, 327, 328, 333 Neural, 118, 127, 237, 271, 274, 280, 296, 299 Neuritis, 43, 299, 302 Neuroblastoma, 59, 299 Neurodermatitis, 156, 161, 299 Neuroendocrine, 10, 12, 17, 59, 162, 163, 173, 299 Neurologic, 43, 299 Neuronal, 21, 25, 56, 59, 175, 249, 299, 306 Neurons, 9, 10, 57, 59, 254, 261, 269, 274, 298, 299, 300, 316, 326, 327 Neuropathy, 244, 300, 335 Neuropeptide, 51, 59, 258, 300 Neurosecretory Systems, 267, 300 Neurotensin, 59, 300 Neurotoxicity, 188, 287, 300 Neurotransmitter, 9, 59, 235, 236, 248, 263, 276, 279, 286, 300, 322, 325, 327 Neurovegetative, 125, 300 Neutrons, 287, 300, 315 Neutrophil, 32, 73, 100, 300 Nicotine, 219, 300 Nitric Oxide, 8, 25, 35, 48, 53, 70, 300 Nitrogen, 238, 239, 259, 270, 272, 276, 288, 300, 304, 331 Norepinephrine, 38, 236, 263, 300 Noxae, 166, 300 Nuclear, 8, 37, 58, 59, 165, 244, 265, 269, 274, 290, 299, 301, 328 Nuclei, 239, 265, 274, 279, 290, 293, 296, 300, 301, 302, 314 Nucleic acid, 235, 280, 283, 298, 300, 301, 319, 335 Nucleic Acid Hybridization, 280, 301 Nucleus, 10, 242, 244, 245, 253, 259, 260, 262, 269, 293, 297, 300, 301, 311, 314, 316 Nursing Care, 301, 305 Nutritional Status, 34, 301 Nutritional Support, 217, 301 O Observational study, 74, 301 Octreotide, 81, 301
Ocular, 40, 43, 64, 84, 94, 100, 118, 161, 162, 167, 176, 272, 301 Oliguria, 288, 301 Oophorectomy, 154, 301 Opacity, 250, 301 Ophthalmic, 43, 150, 157, 167, 179, 200, 202, 203, 301, 310 Ophthalmology, 13, 53, 69, 77, 84, 85, 87, 100, 108, 119, 167, 272, 301 Opiate, 181, 245, 267, 297, 298, 301 Opium, 219, 264, 297, 301, 304 Opsin, 301, 318, 319 Optic Chiasm, 281, 302 Optic disc, 302 Optic Nerve, 238, 302, 303, 314, 318, 320 Optic Nerve Diseases, 302, 314 Optic Neuritis, 43, 118, 221, 302 Orbital, 102, 302 Orthostatic, 301, 302 Osmotic, 237, 296, 302 Osteoarthritis, 14, 302 Osteodystrophy, 219, 302 Osteoporosis, 6, 7, 43, 98, 134, 154, 157, 166, 187, 217, 302 Otitis, 88, 158, 302 Otitis Media, 158, 302 Otitis Media with Effusion, 158, 302 Ouabain, 53, 302 Outpatient, 71, 303 Ovalbumin, 31, 303 Ovarian Follicle, 258, 303 Ovaries, 242, 301, 303, 322 Ovary, 152, 258, 269, 276, 303 Overdose, 231, 303 Ovulation, 152, 292, 303 Ovum, 258, 260, 275, 290, 303, 312 Oxidation, 25, 165, 235, 241, 246, 260, 276, 288, 291, 303, 332 Oxidative metabolism, 290, 303 Oxidative Stress, 34, 303 Oximetry, 29, 303 Oxytocin, 59, 303 P Pachymeningitis, 294, 303 Palliative, 51, 64, 259, 303, 328 Pancreas, 235, 284, 303, 304 Pancreatic, 196, 303, 304, 324 Pancreatic Ducts, 303, 324 Pancreatic Insufficiency, 196, 304 Pancreatitis, 134, 157, 304 Pancytopenia, 40, 304 Paneth Cells, 267, 304
351
Papaverine, 301, 304 Papillary, 281, 304 Papilledema, 304, 314 Paranasal Sinuses, 158, 304, 322, 324 Parasite, 304, 331 Parasitic, 149, 304 Parathyroid, 154, 304, 327 Parathyroid Glands, 304 Parathyroid hormone, 154, 304 Parenteral, 180, 219, 304 Paresis, 299, 304 Paresthesias, 299, 304 Parotid, 67, 305, 319 Partial remission, 305, 317 Particle, 47, 155, 291, 305, 330 Parturition, 152, 305, 312 Patch, 10, 45, 97, 151, 152, 305, 330 Pathogen, 12, 305 Pathologic, 24, 36, 50, 57, 162, 235, 242, 246, 249, 258, 280, 281, 305, 314 Pathologic Processes, 242, 305 Pathologies, 10, 172, 305 Pathophysiology, 13, 21, 34, 46, 54, 60, 64, 82, 186, 305 Patient Care Management, 215, 305 Patient Education, 215, 220, 226, 228, 234, 305 Peak flow, 16, 28, 305 Pelvic, 267, 305, 313, 318 Pelvis, 235, 303, 305, 318, 332 Pemphigus, 92, 235, 305 Pendulous, 153, 305 Penicillin, 218, 240, 305 Penicillin G, 218, 305 Penis, 178, 220, 233, 305, 307, 311 Pentamidine, 186, 305 Peptide, 154, 168, 169, 245, 254, 289, 305, 310, 313, 314 Peptide Chain Elongation, 254, 305 Perception, 67, 78, 103, 306, 320 Percutaneous, 72, 103, 306 Perennial, 23, 280, 306, 331 Perforation, 99, 127, 220, 306 Perfusion, 14, 281, 306 Pericardium, 306, 327 Perinatal, 34, 57, 98, 103, 118, 188, 306 Peripheral blood, 31, 40, 285, 306 Peripheral Nerves, 289, 306 Peripheral Nervous System, 300, 306, 325 Peripheral stem cells, 277, 306 Peripheral Vascular Disease, 60, 306 Peritoneal, 242, 306
Peritoneal Cavity, 242, 306 Peritoneum, 306, 318 Perivascular, 296, 306 Peroxidase, 31, 291, 306 Peroxide, 307 Petrolatum, 266, 307 PH, 106, 247, 307 Phagocytosis, 12, 296, 307 Pharmaceutical Preparations, 269, 307, 312 Pharmacodynamic, 105, 181, 307 Pharmacogenetics, 18, 307 Pharmacokinetic, 92, 103, 105, 307 Pharmacologic, 13, 32, 39, 59, 239, 243, 259, 277, 307, 329 Pharmacotherapy, 77, 91, 106, 181, 307 Phenobarbital, 82, 307 Phenolphthalein, 266, 307 Phenotype, 10, 13, 19, 36, 49, 307 Phenyl, 165, 295, 307 Phenylalanine, 307, 331 Phenytoin, 249, 307 Phimosis, 177, 178, 307 Phorbol, 37, 308 Phorbol Esters, 37, 308 Phosphodiesterase, 157, 308 Phospholipases, 308, 322 Phospholipids, 271, 291, 308 Phosphorus, 219, 248, 304, 308 Phosphorylated, 59, 254, 308 Phosphorylation, 38, 44, 56, 67, 170, 308, 332 Photocoagulation, 14, 254, 308 Physiologic, 15, 26, 47, 58, 68, 168, 237, 246, 277, 286, 294, 308, 312, 316 Physiology, 17, 35, 49, 50, 58, 59, 73, 79, 83, 84, 89, 125, 128, 219, 278, 289, 308, 333 Pigments, 245, 250, 308, 318 Pilot study, 58, 98, 119, 308 Pituitary Gland, 170, 258, 308, 321 Placebo Effect, 51, 308 Placenta, 152, 242, 269, 308, 312 Plaque, 93, 240, 252, 308 Plasma cells, 240, 309 Plasma Exchange, 53, 107, 309 Plasma protein, 153, 237, 267, 309 Plasma Volume, 296, 309 Plasticity, 9, 10, 118, 309 Platelet Activation, 309, 322 Platelet Aggregation, 300, 309, 328 Platelet Transfusion, 53, 309
352
Corticosteroids
Platelets, 300, 304, 309, 316, 328 Pleura, 49, 309 Pneumococcal Infections, 20, 309 Pneumonia, 12, 66, 75, 76, 101, 186, 257, 305, 309 Pneumonitis, 66, 126, 309 Poisoning, 264, 286, 299, 309 Polyarteritis Nodosa, 107, 282, 309 Polyarthritis, 288, 309, 322 Polyethylene, 31, 146, 309 Polymers, 147, 174, 309, 313 Polymorphism, 18, 68, 310 Polymyalgia Rheumatica, 101, 310 Polypeptide, 154, 238, 255, 271, 280, 310, 312, 313, 336 Polyposis, 27, 255, 310 Polysaccharide, 241, 310, 313 Polyunsaturated fat, 128, 310, 328 Polyvinyl Alcohol, 150, 310 Portal Hypertension, 187, 189, 310 Portal Vein, 310 Posterior, 157, 176, 239, 253, 264, 287, 302, 303, 310, 318, 320, 324 Postmenopausal, 7, 154, 302, 310 Postnatal, 56, 77, 97, 104, 221, 310, 325 Postsynaptic, 10, 310, 322, 327 Potassium, 121, 219, 220, 237, 263, 296, 305, 310 Potassium hydroxide, 310 Potentiates, 285, 310 Potentiation, 37, 292, 310, 322 Practicability, 310, 331 Practice Guidelines, 63, 210, 221, 311 Precancerous, 311 Preclinical, 62, 311 Precursor, 240, 242, 259, 263, 265, 267, 268, 300, 307, 311, 312, 331, 332 Predisposition, 166, 311 Prednisolone, 6, 40, 167, 170, 189, 295, 311 Prednisone, 32, 63, 170, 189, 201, 311 Prefrontal Cortex, 62, 311 Pregnancy Outcome, 22, 311 Pregnenolone, 311, 335, 336 Premalignant, 150, 311 Prenatal, 11, 56, 99, 105, 106, 112, 266, 311 Prepuce, 177, 178, 253, 307, 311 Presynaptic, 10, 300, 311, 327 Prevalence, 7, 15, 16, 27, 34, 42, 311 Primary Biliary Cirrhosis, 102, 187, 189, 311 Primum, 101, 311 Probe, 21, 311
Procaine, 290, 311 Proctitis, 134, 191, 312 Proctocolectomy, 218, 312 Proctosigmoiditis, 191, 312 Prodrug, 312 Progesterone, 61, 152, 312, 325 Progression, 8, 13, 31, 90, 180, 240, 312 Projection, 300, 302, 311, 312 Prolactin, 125, 312 Promoter, 9, 27, 36, 37, 38, 42, 49, 50, 59, 312 Promotor, 312, 317 Prone, 153, 312 Prophylaxis, 6, 70, 98, 117, 154, 166, 269, 312 Propolis, 149, 312 Propylene Glycol, 170, 312 Prospective study, 15, 16, 94, 312 Prostaglandin, 32, 126, 148, 240, 312, 328 Prostaglandins A, 170, 283, 312, 313 Prostaglandins D, 313 Prostaglandins, Synthetic, 284, 313 Prostate, 13, 128, 313 Prosthesis, 220, 313 Protease, 52, 91, 157, 255, 313 Protease Inhibitors, 91, 313 Protective Agents, 249, 313 Protein C, 37, 147, 237, 238, 291, 313 Protein Conformation, 238, 313 Protein Kinases, 59, 313 Protein S, 246, 254, 269, 279, 299, 313, 328 Proteins, 14, 37, 44, 45, 47, 49, 53, 56, 63, 65, 147, 238, 241, 247, 250, 251, 253, 255, 269, 270, 276, 279, 280, 283, 285, 294, 297, 300, 305, 308, 309, 310, 313, 314, 316, 319, 322, 330 Proteinuria, 4, 5, 50, 275, 299, 313 Proteoglycans, 245, 270, 313 Proteolytic, 177, 178, 238, 256, 271, 314 Protocol, 16, 19, 22, 23, 43, 65, 314 Protons, 280, 287, 314, 315 Protozoa, 289, 296, 314, 324, 331 Proximal, 47, 49, 190, 250, 263, 298, 310, 311, 314, 321 Pruritic, 170, 261, 265, 290, 314 Pruritus, 187, 261, 299, 314, 332 Pseudomonas, 153, 314 Pseudotumor Cerebri, 157, 314 Psoriasis, 72, 87, 134, 149, 155, 156, 157, 161, 165, 235, 254, 262, 269, 298, 314 Psychiatric, 60, 157, 181, 295, 314
353
Psychiatry, 21, 34, 39, 62, 88, 93, 104, 182, 272, 314, 333 Psychic, 290, 295, 314, 321 Psychoactive, 314, 328, 335 Psychogenic, 299, 314 Psychotomimetic, 239, 262, 314 Psychotropic, 219, 314 Psyllium, 140, 314 Public Health, 20, 30, 118, 210, 314 Public Policy, 209, 315 Publishing, 5, 65, 165, 315 Pulmonary Artery, 247, 315, 333 Pulmonary Edema, 288, 315 Pulmonary Fibrosis, 32, 315 Pulmonary hypertension, 258, 315 Pulmonary Sarcoidosis, 85, 315 Pulse, 29, 232, 297, 303, 315 Pupil, 258, 302, 315 Purpura, 52, 76, 89, 166, 315 Q Quality of Health Care, 315, 330 Quality of Life, 14, 22, 43, 59, 85, 101, 127, 130, 195, 197, 315 Quiescent, 315, 334 R Race, 4, 54, 237, 296, 315 Racemic, 237, 315 Radiation, 244, 270, 272, 273, 280, 281, 282, 283, 285, 287, 294, 295, 315, 316, 317, 319, 335 Radiation therapy, 270, 273, 280, 285, 287, 315, 335 Radioactive, 244, 247, 277, 280, 283, 285, 287, 291, 297, 301, 315, 319, 335 Radiolabeled, 45, 287, 315, 335 Radiological, 306, 315 Radiotherapy, 247, 287, 315, 316, 335 Randomized clinical trial, 22, 28, 29, 40, 63, 316 Randomized Controlled Trials, 4, 5, 189, 316 RANTES, 48, 316 Raphe Nuclei, 18, 316 Reactivation, 92, 96, 316 Reagent, 163, 292, 316, 319 Reagin, 261, 316 Receptors, Serotonin, 316, 321 Recombinant, 42, 44, 151, 316, 333 Recombination, 274, 316 Rectal, 134, 200, 217, 218, 220, 316 Rectum, 190, 218, 220, 242, 244, 247, 255, 262, 274, 284, 289, 312, 313, 316, 322
Recurrence, 4, 23, 106, 187, 197, 246, 253, 317 Red blood cells, 49, 219, 269, 278, 317, 319 Reductase, 25, 26, 34, 242, 295, 317 Refer, 1, 13, 248, 255, 263, 267, 272, 279, 291, 292, 300, 317, 321, 329 Refraction, 317, 323 Refractive Errors, 238, 317 Refractometry, 14, 317 Refractory, 3, 53, 58, 87, 107, 191, 196, 317 Regeneration, 10, 36, 38, 317 Regimen, 5, 28, 43, 161, 189, 265, 307, 308, 317 Regional lymph node, 251, 317 Relapse, 6, 52, 181, 190, 317 Relaxant, 304, 307, 317 Remission, 3, 5, 59, 76, 96, 105, 128, 189, 197, 235, 246, 293, 317 Renal tubular, 46, 317 Renin, 11, 240, 317 Resection, 50, 218, 317 Residual Volume, 48, 317 Respiration, 75, 82, 83, 85, 242, 249, 259, 296, 297, 303, 317 Respirator, 294, 317 Respiratory distress syndrome, 56, 61, 248, 317 Respiratory failure, 61, 180, 317 Response Elements, 59, 317 Response rate, 50, 318 Reticular, 153, 195, 318 Retina, 57, 66, 253, 257, 262, 289, 302, 315, 318, 319, 333, 334 Retinal, 82, 247, 262, 302, 318, 319, 334 Retinoid, 161, 235, 269, 318 Retinol, 318, 319 Retraction, 55, 318 Retrobulbar, 302, 318 Retrograde, 10, 286, 318 Retroperitoneal, 105, 236, 318 Retroperitoneal Fibrosis, 105, 318 Retroperitoneal Space, 318 Retrospective, 42, 74, 89, 318 Retroviral vector, 274, 318 Reversion, 57, 318, 331 Rhamnose, 302, 318 Rheumatic Diseases, 72, 73, 116, 318 Rheumatoid, 14, 39, 64, 72, 82, 87, 92, 116, 135, 148, 149, 157, 166, 214, 255, 318 Rheumatoid arthritis, 14, 39, 64, 72, 82, 87, 92, 116, 148, 149, 157, 166, 255, 318 Rhinitis, 81, 91, 99, 319
354
Corticosteroids
Rhodopsin, 302, 318, 319 Ribonucleic acid, 48, 319 Ribose, 236, 319 Rigidity, 308, 319, 320 Risk factor, 4, 7, 14, 19, 50, 159, 162, 171, 312, 319 Rod, 244, 254, 314, 319 Rosiglitazone, 58, 319 Rubidium, 53, 319 S Salicylic, 149, 156, 319 Saline, 248, 309, 319 Saliva, 172, 295, 319 Salivary, 126, 127, 128, 129, 186, 260, 319, 322 Salivary glands, 260, 319, 322 Saponins, 319, 325 Sarcoidosis, 75, 82, 83, 135, 319 Sarcoma, 92, 96, 271, 319 Scans, 39, 319 Schizoid, 320, 335 Schizophrenia, 250, 265, 320, 335 Schizophrenia, Catatonic, 250, 320 Schizotypal Personality Disorder, 320, 335 Sclera, 40, 253, 257, 268, 320, 333 Scleritis, 40, 320 Scleroderma, 93, 135, 270, 320 Sclerosis, 74, 134, 255, 298, 320 Screening, 28, 110, 254, 320, 332 Sebaceous, 37, 262, 287, 320, 334 Sebaceous gland, 37, 262, 287, 320, 334 Sebum, 320 Secretory, 11, 45, 152, 320, 327 Sedative, 252, 254, 320 Sediment, 320, 332 Sedimentation, 310, 320 Segmental, 50, 275, 320 Segmentation, 320 Seizures, 56, 249, 307, 321 Selective estrogen receptor modulator, 321, 327 Selenium, 117, 121, 125, 321 Sella, 308, 321 Sella Turcica, 308, 321 Semen, 313, 321 Semicircular canal, 284, 321 Semisynthetic, 254, 321 Senile, 154, 302, 321 Sensitization, 31, 321 Sensor, 34, 174, 321 Sepsis, 35, 76, 79, 119, 158, 321 Septal, 99, 290, 321
Septic, 76, 106, 119, 158, 243, 321 Septum, 172, 298, 311, 321 Septum Pellucidum, 321 Sequencing, 34, 321 Serologic, 282, 321 Serotonin, 18, 24, 300, 307, 316, 321, 331 Serous, 77, 84, 108, 267, 309, 322 Sex Characteristics, 236, 239, 322, 327 Shock, 37, 55, 76, 106, 119, 135, 158, 280, 322, 330 Sicca, 64, 322 Sigmoid, 191, 312, 322 Sigmoid Colon, 191, 312, 322 Sigmoidoscopy, 217, 322 Signal Transduction, 24, 33, 35, 46, 59, 322 Signs and Symptoms, 217, 309, 317, 322, 332 Sinusitis, 79, 135, 158, 171, 172, 322 Sirolimus, 102, 203, 283, 322 Skeletal, 116, 152, 175, 239, 254, 259, 322 Skeleton, 235, 271, 288, 312, 322 Skull, 172, 322, 327 Sleep apnea, 101, 323 Small intestine, 27, 218, 220, 251, 252, 257, 264, 275, 279, 282, 286, 323 Smallpox, 214, 323 Smoking Cessation, 29, 323 Smooth muscle, 243, 248, 249, 257, 279, 297, 304, 323, 325 Social Environment, 315, 323 Social Security, 316, 323 Sodium, 49, 175, 179, 216, 219, 237, 263, 276, 296, 305, 323, 326 Soft tissue, 247, 271, 322, 323 Solid tumor, 246, 264, 323 Solvent, 176, 269, 302, 312, 323 Somatic, 236, 280, 290, 296, 306, 311, 323 Soybean Oil, 310, 323 Space Flight, 188, 323 Spatial disorientation, 263, 323 Specialist, 222, 323 Specificity, 9, 13, 21, 50, 65, 164, 237, 249, 323 Spectrum, 161, 169, 191, 288, 296, 323 Sperm, 239, 253, 324 Sphenoid, 172, 304, 321, 324 Sphenoid Sinus, 324 Sphincter, 81, 289, 324 Sphincter of Oddi, 81, 324 Spinal cord, 70, 243, 251, 253, 265, 274, 294, 299, 300, 303, 306, 324 Spinous, 268, 324
355
Spirometry, 29, 30, 324 Spleen, 260, 292, 319, 324 Splenectomy, 53, 66, 89, 324 Spontaneous Abortion, 311, 324 Sporadic, 27, 324 Spores, 34, 324 Sprue, 196, 324 Sputum, 22, 29, 36, 42, 324 Squamous, 64, 156, 162, 195, 268, 288, 324 Squamous cell carcinoma, 195, 268, 288, 324 Squamous cells, 324 Stabilizer, 40, 324 Staging, 319, 324 Standard therapy, 22, 28, 59, 157, 324 Steady state, 53, 173, 324 Steatosis, 271, 324 Steel, 254, 325 Stem Cells, 36, 306, 325 Sterile, 28, 162, 243, 304, 325 Sterility, 259, 325 Steroid therapy, 31, 63, 149, 325 Stillbirth, 311, 325 Stimulant, 239, 262, 279, 325 Stimulus, 51, 166, 238, 264, 265, 269, 284, 286, 304, 325, 328 Stomach, 136, 235, 244, 262, 269, 274, 276, 279, 298, 306, 323, 324, 325 Stool, 217, 218, 255, 257, 287, 289, 325, 327 Stool test, 218, 325 Stroke, 14, 34, 159, 162, 171, 208, 250, 325 Stromal, 54, 267, 325 Subacute, 284, 322, 325 Subcapsular, 157, 325, 335 Subclinical, 65, 284, 321, 325 Subcutaneous, 157, 236, 265, 291, 304, 325 Subiculum, 279, 325 Subspecies, 323, 325 Substance P, 269, 295, 320, 325 Substrate, 44, 268, 291, 326 Suction, 271, 326 Sudden death, 31, 326 Sulfates, 144, 326 Sulfur, 270, 289, 326 Sulfuric acid, 326 Superior Cervical Ganglion, 14, 326 Supplementation, 5, 117, 125, 130, 326 Support group, 218, 326 Suppression, 6, 10, 30, 149, 157, 166, 168, 187, 254, 326 Surface Plasmon Resonance, 44, 326 Surfactant, 44, 146, 326, 335
Suspensions, 150, 326 Sweat, 252, 262, 295, 326 Sweat Glands, 252, 262, 326 Sympathomimetic, 239, 262, 263, 268, 300, 326 Symphysis, 252, 313, 326 Symptomatic, 29, 154, 195, 217, 304, 326 Synapse, 236, 311, 326, 327, 330 Synaptic, 292, 300, 305, 322, 327 Synaptic Transmission, 300, 305, 327 Synergistic, 68, 147, 149, 178, 179, 312, 327 Systemic lupus erythematosus, 7, 64, 67, 74, 95, 157, 186, 255, 282, 327 Systolic, 163, 281, 327 Systolic blood pressure, 163, 327 T Tacrolimus, 94, 102, 103, 283, 327 Tamoxifen, 105, 321, 327 Tear Gases, 287, 327 Temporal, 21, 101, 239, 279, 310, 327 Temporal Lobe, 21, 239, 327 Tenesmus, 191, 327 Testis, 25, 269, 327 Testosterone, 21, 25, 59, 61, 66, 126, 154, 162, 163, 172, 239, 317, 327 Tetany, 304, 327 Tetracycline, 45, 327 Tetrahydrocannabinol, 249, 328 Thalamus, 290, 311, 328 Theophylline, 30, 101, 328 Therapeutics, 6, 37, 85, 129, 204, 328 Thigh, 271, 328 Third Ventricle, 281, 328 Thoracic, 48, 75, 82, 83, 85, 293, 294, 309, 328, 335 Threshold, 261, 269, 281, 328 Thrombin, 271, 309, 313, 328 Thrombocytes, 166, 309, 328 Thrombomodulin, 313, 328 Thrombosis, 8, 313, 325, 328 Thromboxanes, 242, 265, 328 Thrush, 249, 328 Thymidine, 37, 328 Thymidine Kinase, 37, 328 Thymoma, 88, 92, 328 Thymus, 282, 292, 328, 329 Thyroid, 57, 68, 126, 298, 304, 329, 331 Thyroid Gland, 298, 304, 329 Thyroid Hormones, 126, 329, 331 Thyroxine, 237, 307, 329 Tinnitus, 302, 314, 329 Tolerance, 33, 171, 235, 276, 329
356
Corticosteroids
Tomography, 329 Tone, 11, 329 Tonicity, 286, 329 Tonus, 329 Tooth Preparation, 236, 329 Torsion, 284, 329 Toxic, iv, 51, 56, 176, 238, 243, 259, 260, 262, 282, 291, 294, 300, 305, 310, 321, 329, 335 Toxicity, 21, 30, 31, 42, 51, 58, 60, 67, 92, 160, 264, 329 Toxicology, 60, 72, 94, 106, 124, 210, 329 Toxin, 267, 329 Trabecular Meshwork, 14, 330 Trace element, 272, 330 Tracer, 279, 330 Trachea, 248, 289, 329, 330 Traction, 254, 330 Transcriptase, 289, 330, 335 Transcription Factors, 27, 37, 58, 61, 317, 330 Transdermal, 151, 152, 330 Transduction, 25, 59, 322, 330 Transfection, 246, 274, 330 Transfer Factor, 282, 330 Transferases, 276, 330 Transfusion, 53, 330 Translation, 269, 299, 330 Translational, 19, 330 Translocation, 254, 269, 330 Transmitter, 235, 243, 263, 286, 294, 300, 330 Transplantation, 4, 39, 100, 102, 103, 158, 187, 266, 282, 288, 293, 330 Trauma, 70, 86, 147, 162, 164, 168, 244, 299, 304, 329, 330 Treatment Failure, 55, 330 Treatment Outcome, 63, 330 Trees, 268, 331 Triamcinolone Acetonide, 170, 331 Trichomoniasis, 295, 331 Tricuspid Atresia, 258, 331 Triglyceride, 155, 281, 331 Trophic, 9, 57, 331 Trypanosomiasis, 305, 331 Tryptophan, 255, 321, 331 Tuberculosis, 216, 292, 319, 331 Tumor Lysis Syndrome, 116, 331 Tumor Necrosis Factor, 48, 190, 331 Tumour, 182, 274, 331 Tunica, 266, 297, 331 Typhimurium, 46, 331
Tyrosine, 38, 263, 331 U Ulcer, 118, 264, 331, 333 Ulcerative colitis, 27, 58, 189, 190, 197, 216, 217, 218, 284, 331 Ultrasonography, 98, 331 Unconscious, 239, 332 Uncoupling Agents, 287, 332 Uraemia, 304, 332 Uremia, 288, 332 Ureters, 318, 332 Urethra, 305, 313, 332 Uric, 238, 276, 281, 332 Urinalysis, 29, 332 Urinary, 45, 65, 84, 89, 125, 153, 244, 249, 253, 301, 332, 335 Urine, 5, 29, 31, 65, 78, 96, 153, 216, 231, 242, 244, 246, 259, 263, 288, 301, 313, 332 Urine Testing, 216, 332 Urokinase, 169, 332 Ursodeoxycholic Acid, 187, 189, 332 Urticaria, 157, 332 Uterine Contraction, 303, 332 Uterus, 252, 258, 260, 267, 293, 295, 300, 303, 312, 332, 333 Uvea, 333 Uveal tract, 315, 333 Uveitis, 40, 136, 333 V Vaccine, 20, 314, 333 Vagina, 249, 252, 294, 333 Vaginal, 136, 152, 215, 292, 333 Vaginitis, 136, 249, 333 Varicose, 289, 333 Varicose Ulcer, 289, 333 Vascular, 8, 40, 164, 249, 253, 262, 267, 284, 300, 303, 308, 329, 332, 333 Vasculitis, 82, 107, 304, 309, 333 Vasodilator, 241, 248, 264, 279, 304, 333 Vector, 330, 333 Vegetative, 300, 333 Vein, 60, 286, 301, 305, 310, 333 Venereal, 150, 333 Venous, 289, 313, 331, 333 Ventilation, 333 Ventricle, 239, 243, 258, 279, 315, 327, 328, 331, 333 Ventricular, 8, 258, 331, 333 Venules, 247, 249, 267, 333 Vertebrae, 324, 333 Vertebral, 98, 333 Vertigo, 302, 333
357
Vesicular, 243, 261, 279, 323, 334 Vestibule, 254, 284, 321, 334 Veterinarians, 153, 334 Veterinary Medicine, 209, 334 Villous, 251, 334 Vinca Alkaloids, 334 Vincristine, 128, 334 Viral, 23, 51, 54, 149, 196, 235, 258, 266, 330, 334, 335 Virulence, 35, 243, 329, 334 Virus, 34, 53, 66, 74, 86, 91, 107, 133, 149, 267, 274, 280, 285, 308, 318, 323, 330, 334 Visceral, 49, 162, 244, 289, 290, 306, 334 Viscosity, 152, 235, 334 Visual Acuity, 257, 302, 320, 334 Visual Cortex, 238, 334 Visual field, 302, 314, 334 Vitiligo, 111, 215, 334 Vitreous, 176, 262, 289, 318, 334 Vitreous Body, 318, 334 Vitro, 11, 13, 14, 27, 31, 33, 35, 38, 46, 49, 52, 54, 56, 59, 60, 61, 63, 66, 67, 144, 167, 172, 266, 274, 283, 327, 334 Vivo, 11, 12, 13, 24, 25, 27, 31, 33, 35, 37, 40, 44, 49, 52, 53, 56, 57, 59, 60, 61, 151, 274, 283, 291, 293, 327, 328, 334
Vulgaris, 87, 157, 235, 334 W Wart, 150, 335 Wetting Agents, 196, 335 Wheezing, 19, 29, 54, 180, 335 White blood cell, 5, 240, 277, 292, 293, 297, 298, 300, 309, 335 Windpipe, 248, 267, 329, 335 Withdrawal, 112, 181, 295, 335 Wound Healing, 8, 36, 60, 64, 136, 157, 294, 335 X Xanthine, 238, 335 Xanthine Oxidase, 238, 335 Xenograft, 13, 240, 335 X-ray, 217, 244, 247, 256, 272, 287, 301, 315, 316, 319, 324, 335 X-ray therapy, 287, 335 Y Yeasts, 169, 249, 273, 307, 335 Z Zalcitabine, 289, 335 Zona Fasciculata, 164, 335, 336 Zona Glomerulosa, 11, 335 Zona Reticularis, 164, 336 Zymogen, 313, 336
358
Corticosteroids
359
360
Corticosteroids
