Etodolac - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

ETODOLAC A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P...

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

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Etodolac: 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: 0-497-00425-9 1. Etodolac-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on etodolac. 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 ETODOLAC ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Etodolac......................................................................................... 4 The National Library of Medicine: PubMed .................................................................................. 5 CHAPTER 2. NUTRITION AND ETODOLAC ...................................................................................... 27 Overview...................................................................................................................................... 27 Finding Nutrition Studies on Etodolac ....................................................................................... 27 Federal Resources on Nutrition ................................................................................................... 31 Additional Web Resources ........................................................................................................... 32 CHAPTER 3. ALTERNATIVE MEDICINE AND ETODOLAC ................................................................ 33 Overview...................................................................................................................................... 33 National Center for Complementary and Alternative Medicine.................................................. 33 Additional Web Resources ........................................................................................................... 35 General References ....................................................................................................................... 36 CHAPTER 4. PATENTS ON ETODOLAC ............................................................................................. 37 Overview...................................................................................................................................... 37 Patents on Etodolac...................................................................................................................... 37 Patent Applications on Etodolac .................................................................................................. 45 Keeping Current .......................................................................................................................... 47 CHAPTER 5. PERIODICALS AND NEWS ON ETODOLAC................................................................... 49 Overview...................................................................................................................................... 49 News Services and Press Releases................................................................................................ 49 Academic Periodicals covering Etodolac ...................................................................................... 51 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 53 Overview...................................................................................................................................... 53 U.S. Pharmacopeia....................................................................................................................... 53 Commercial Databases ................................................................................................................. 54 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 59 Overview...................................................................................................................................... 59 NIH Guidelines............................................................................................................................ 59 NIH Databases............................................................................................................................. 61 Other Commercial Databases....................................................................................................... 63 APPENDIX B. PATIENT RESOURCES ................................................................................................. 65 Overview...................................................................................................................................... 65 Patient Guideline Sources............................................................................................................ 65 Finding Associations.................................................................................................................... 67 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 69 Overview...................................................................................................................................... 69 Preparation................................................................................................................................... 69 Finding a Local Medical Library.................................................................................................. 69 Medical Libraries in the U.S. and Canada ................................................................................... 69 ONLINE GLOSSARIES.................................................................................................................. 75 Online Dictionary Directories ..................................................................................................... 75 ETODOLAC DICTIONARY .......................................................................................................... 77 INDEX .............................................................................................................................................. 105

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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 etodolac 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 etodolac, 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 etodolac, 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 etodolac. 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 etodolac, 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 etodolac. 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 ETODOLAC Overview In this chapter, we will show you how to locate peer-reviewed references and studies on etodolac.

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

Preventing Gastrointestinal Complications of NSAIDs: Risk Factors, Recent Advances, and Latest Strategies Source: Postgraduate Medicine. 109(5): 117-120, 123-128. May 2001. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: In the United States, gastrointestinal complications induced by nonsteroidal antiinflammatory drugs (NSAIDs) cause more than 100,000 hospitalizations and an estimated 16,500 deaths annually. Because serious gastrointestinal events can occur without warning, prevention measures must not rely on warning signs alone. This article discusses the epidemiology of NSAID induced toxic episodes, reviews the risk factors for these occurrences, and offers strategies for minimizing the risk among long

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term NSAID users. Risk factors for toxicity include older age and history of ulcer. To minimize the risk of gastrointestinal complications, prescribers should avoid NSAIDs or use NSAIDs at the lowest effective dose. If long term NSAID therapy is required, prescribers should avoid concomitant use of oral corticosteroids, anticoagulants, or more than one NSAID. In most patients with no risk factors, the effects of gastrointestinal toxicity can be minimized by prescribing the lowest effective dose of ibuprofen, salsalate, etodolac, or nabumetone. In patients with two or more risk factors, concomitant misoprostol use is cost effective with long term NSAID therapy. The cost effectiveness for concomitant omeprazole use is not known. Prophylactic omeprazole may be reserved for high risk patients who do not tolerate misoprostol. In other patients, it may be less cost effective. Because ranitidine is inferior to omeprazole in endoscopic studies, it is not recommended for prophylaxis. 6 tables. 26 references.

Federally Funded Research on Etodolac The U.S. Government supports a variety of research studies relating to etodolac. 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 etodolac. 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 etodolac. The following is typical of the type of information found when searching the CRISP database for etodolac: •

Project Title: REGULATION LYMPHOCYTES

OF

SENESCENCE

AND

APOPTOSIS

IN

Principal Investigator & Institution: Carson, Dennis A.; Professor; Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 30-JUN-1976; Project End 31-JAN-2004 Summary: (appended verbatim from investigator's abstract): Abnormalities in the regulation of Iymphocyte senescence and apoptosis are fundamental to the pathogenesis of lymphoproliferative diseases, and also play a role in the progression of autoimmune syndromes. The overall goal of this research grant is to identify these abnormalities, and to exploit the information pharmacologically for the development of better treatments for these disabling and often fatal ailments. Experiments supported by this grant since the last competitive review four years ago: (i) have demonstrated that purine deoxynucleosides with anti lymphocyte activity can directly stimulate Apaf 1 dependent caspase activation; (ii) have synthesized and analyzed novel substantiated indanones that induce apoptosis in chronic lymphocytic leukemia (CLL) cells without harming 2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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normal lymphocytes; (iii) have shown that the non steroidal anti inflammatory drug etodolac can depress malignant Iymphocyte counts in CLL patients; and (iv) have revealed that both the R and S enantiomers of etodolac interfere with mitochondrial respiration in CLL cells, cause rapid degradation of the anti apoptotic protein Mcl 1, and activate the nuclear hormone receptor PPARy. Based upon this progress, the specific aims of the renewal application are (1) to study in detail how different purine nucleosides interact with components of the apoptotic machinery in normal and malignant lymphocytes; (2) to clarify the biochemical basis for the selective toxicity of substituted indanones to malignant B cells, emphasizing changes in the cytoskeleton and cell death receptor expression; (3) to analyze the importance of PPARy, Mcl 1, and mitochondria in the regulation of cell survival in Iymphocytes, using R etodolac as a pharmacologic probe; and (4) to test the clinical activity of R etodolac in lymphoproliferative diseases and multiple myeloma. The proposed experiments differ from most other studies of apoptosis regulation because of their focus on quiescent cells, their utilization of lymphocytes taken directly from patients, and their aim to translate results quickly to the clinic. When complete, these experiments should enhance current knowledge of the factors that regulate senescence and apoptosis in non dividing lymphocytes, and could lead to less toxic and more effective therapies for lymphoproliferative and possibly autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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.3 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 etodolac, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “etodolac” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for etodolac (hyperlinks lead to article summaries): •

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A comparative study of the efficacy and toxicity of etodolac and naproxen in the treatment of osteoarthritis. Author(s): Chikanza IC, Clarke B, Hopkins R, MacFarlane DG, Bird H, Grahame R. Source: Br J Clin Pract. 1994 March-April; 48(2): 67-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8024992

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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A comparison of etodolac (Ultradol) with acetaminophen plus codeine (Tylenol #3) in controlling post-surgical pain in vasectomy patients. Author(s): Casey R, Zadra J, Khonsari H. Source: Current Medical Research and Opinion. 1997; 13(10): 555-63. Erratum In: Curr Med Res Opin 1997; 14(1): 63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9327190

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A comparison of the effects of etodolac and ibuprofen on renal haemodynamics, tubular function, renin, vasopressin and urinary excretion of albumin and alphaglutathione-S-transferase in healthy subjects: a placebo-controlled cross-over study. Author(s): Svendsen KB, Bech JN, Sorensen TB, Pedersen EB. Source: European Journal of Clinical Pharmacology. 2000 August; 56(5): 383-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11009046

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A comparison of the efficacy of etodolac SR (Lodine SR) and etodolac (Lodine) in patients with rheumatoid arthritis or osteoarthritis. Author(s): Dreiser RL. Source: Rheumatology International. 1993; 13(2 Suppl): S13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8210919

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A double-blind comparison of etodolac and piroxicam in the treatment of osteoarthritis. Author(s): Freitas GG. Source: Current Medical Research and Opinion. 1990; 12(4): 255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150187

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A double-blind gastroscopic evaluation of the effects of etodolac and naproxen on the gastrointestinal mucosa of rheumatic patients. Author(s): Bianchi Porro G, Caruso I, Petrillo M, Montrone F, Ardizzone S. Source: Journal of Internal Medicine. 1991 January; 229(1): 5-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1825323

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A global safety evaluation of etodolac. Author(s): Karbowski A. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 73-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525986

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A randomized double-blind comparison of placebo, etodolac, and naproxen on gastrointestinal injury and prostaglandin production. Author(s): Laine L, Sloane R, Ferretti M, Cominelli F. Source: Gastrointestinal Endoscopy. 1995 November; 42(5): 428-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8566633

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A review of the antiarthritic efficacy and safety of etodolac. Author(s): Zvaifler N. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 43-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525982

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Acute colitis associated with etodolac. Author(s): Wilcox GM, Porensky RS. Source: Journal of Clinical Gastroenterology. 1997 July; 25(1): 367-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9412924

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Agranulocytosis associated with etodolac. Author(s): Cramer RL, Aboko-Cole VC, Gualtieri RJ. Source: The Annals of Pharmacotherapy. 1994 April; 28(4): 458-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8038466

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Albumin binding sites for etodolac enantiomers. Author(s): Mignot I, Presle N, Lapicque F, Monot C, Dropsy R, Netter P. Source: Chirality. 1996; 8(3): 271-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8777148

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An endoscopic comparison of the effects of etodolac, indomethacin, ibuprofen, naproxen, and placebo on the gastrointestinal mucosa. Author(s): Lanza F, Rack MF, Lynn M, Wolf J, Sanda M. Source: The Journal of Rheumatology. 1987 April; 14(2): 338-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2955117

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An endoscopic evaluation of the effects of etodolac and diclofenac on the gastric and duodenal mucosa. Author(s): van Eeden A, Schotborgh RH, Tytgat GN. Source: Clinical Therapeutics. 1990 November-December; 12(6): 496-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2149673

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An overview of the efficacy of etodolac in arthritic disorders. Author(s): Bacon PA. Source: Eur J Rheumatol Inflamm. 1990; 10(1): 22-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146130

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An updated safety profile of etodolac in several thousand patients. Author(s): Schattenkirchner M. Source: Eur J Rheumatol Inflamm. 1990; 10(1): 56-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146132

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Application of a stereospecific high-performance liquid chromatography assay to a pharmacokinetic study of etodolac enantiomers in humans. Author(s): Jamali F, Mehvar R, Lemko C, Eradiri O. Source: Journal of Pharmaceutical Sciences. 1988 November; 77(11): 963-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2976091

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Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories). Author(s): Molina-Martinez IT, Herrero R, Gutierrez JA, Iglesias JM, Fabregas JL, Martinez-Tobed A, Cadorniga R. Source: Journal of Pharmaceutical Sciences. 1993 February; 82(2): 211-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8445537

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Bioavailability studies with etodolac in dogs and man. Author(s): Kraml M, Cosyns L, Hicks DR, Simon J, Mullane JF, Dvornik D. Source: Biopharmaceutics & Drug Disposition. 1984 January-March; 5(1): 63-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6231062

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Capillary electrochromatography-electrospray ionization mass spectrometry for the qualitative investigation of the drug etodolac and its metabolites in biological samples. Author(s): Strickmann DB, Blaschke G. Source: J Chromatogr B Biomed Sci Appl. 2000 October 1; 748(1): 213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11092600

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Chiral bioequivalence: effect of absorption rate on racemic etodolac. Author(s): Boni JR, Korth-Bradley JM, Richards LS, Chiang ST, Hicks DR, Benet LZ. Source: Clinical Pharmacokinetics. 2000 December; 39(6): 459-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11192477

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Clinical efficacy and safety profile of etodolac: focus on the elderly. Author(s): Bacon PA. Source: Eur J Rheumatol Inflamm. 1994; 14(1): 1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744122

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Clinical performance of etodolac in patients with osteoarthritis and rheumatoid arthritis. Author(s): Veys EM. Source: Eur J Rheumatol Inflamm. 1994; 14(1): 23-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744125

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Clinical response to etodolac in the management of pain. Author(s): Mizraji M. Source: Eur J Rheumatol Inflamm. 1990; 10(1): 35-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1699764

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Clinical use of etodolac for the treatment of lumbar disc herniation. Author(s): Hatori M, Kokubun S. Source: Current Medical Research and Opinion. 1999; 15(3): 193-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10621926

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Comparative effects of etodolac, indomethacin, and benoxaprofen on icosanoid biosynthesis. Author(s): Sirois P, Saura C, Salari H, Borgeat P. Source: Inflammation. 1984 December; 8(4): 353-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6240459

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Comparative efficacy of etodolac and placebo in rheumatoid arthritic patients. Author(s): Vetter G, Placchi M, Joubert L. Source: Int J Clin Pharmacol Ther Toxicol. 1982 May; 20(5): 240-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6212555

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Comparison of etodolac and diclofenac in osteoarthritis of the knee. Author(s): Grisanti AM, Vaz AA, Samara AM. Source: Clinical Therapeutics. 1992 November-December; 14(6): 791-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1286486

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Comparison of etodolac, aspirin and placebo for pain after oral surgery. Author(s): Gaston GW, Mallow RD, Frank JE. Source: Pharmacotherapy. 1986 September-October; 6(5): 199-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2948162

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Comparison of etodolac, zomepirac, and placebo for relief of pain after oral surgery. Author(s): Giglio JA, Campbell RL. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1986 October; 44(10): 765-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2944997

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Comparison of the effects of etodolac SR and naproxen on gastro-intestinal blood loss. Author(s): Leese P. Source: Current Medical Research and Opinion. 1992; 13(1): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1468240

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Etodolac

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Comparison of the efficacy and safety of etodolac and piroxicam in patients with rheumatoid arthritis. Etodolac Study 326 Rheumatoid Arthritis Investigators Group. Author(s): Lightfoot R. Source: J Rheumatol Suppl. 1997 February; 47: 10-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035015

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Comparison of three radioligands, selenium-75, lodine-125, and tritium, in the radioimmunoassay of methotrexate. Author(s): Paxton JW, Rowell FJ, Cree GM. Source: Clinical Chemistry. 1978 September; 24(9): 1534-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=688614

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Concomitant etodolac affects neither the unbound clearance nor the pharmacologic effect of warfarin. Author(s): Ermer JC, Hicks DR, Wheeler SC, Kraml M, Jusko WJ. Source: Clinical Pharmacology and Therapeutics. 1994 March; 55(3): 305-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8143396

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Conventional and extended-release etodolac for postsurgical dental pain. Author(s): Hersh EV, Levin LM, Cooper SA, Reynolds D, Gallegos LT, McGoldrick K, Appel A. Source: Clinical Therapeutics. 1999 August; 21(8): 1333-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10485505

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Covalent binding of etodolac acyl glucuronide to albumin in vitro. Author(s): Smith PC, Song WQ, Rodriguez RJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1992 November-December; 20(6): 962-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1362954

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Disposition and biotransformation of 14C-etodolac in man. Author(s): Ferdinandi ES, Sehgal SN, Demerson CA, Dubuc J, Zilber J, Dvornik D, Cayen MN. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1986 February; 16(2): 153-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2938343

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Double blind evaluation of the long-term effects of etodolac versus ibuprofen in patients with rheumatoid arthritis. Author(s): Neustadt DH. Source: J Rheumatol Suppl. 1997 February; 47: 17-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035016

Studies

11

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Double-blind comparison of etodolac and diclofenac in patients with rheumatoid arthritis. Author(s): Lonauer G, Tisscher JR, Lim HG, Bijlsma JW. Source: Current Medical Research and Opinion. 1993; 13(2): 70-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8325044

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Double-blind comparison of etodolac and naproxen in the treatment of rheumatoid arthritis. Author(s): de Queiros MF. Source: Clinical Therapeutics. 1991 January-February; 13(1): 38-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1827613

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Double-blind comparison of etodolac and piroxicam in patients with rheumatoid arthritis. Author(s): Schattenkirchner M. Source: Current Medical Research and Opinion. 1991; 12(8): 497-506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1837260

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Double-blind comparison of etodolac and piroxicam in the treatment of rheumatoid arthritis. Author(s): Dick WC, Franchimont P, Veys E. Source: Clinical Therapeutics. 1993 January-February; 15(1): 148-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8458044

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

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Double-blind comparison of the efficacy and safety of etodolac SR 600 mg u.i.d. and of tenoxicam 20 mg u.i.d. in elderly patients with osteoarthritis of the hip and of the knee. Author(s): Perpignano G, Bogliolo A, Puccetti L. Source: Int J Clin Pharmacol Res. 1994; 14(5-6): 203-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7672877

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Double-blind evaluation of etodolac (200 mg, 400 mg) compared with zomepirac (100 mg) and placebo on third molar extraction pain. Author(s): Scott R, Ellis E 3rd, Upton LG. Source: Oral Surg Oral Med Oral Pathol. 1986 December; 62(6): 638-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2948143

12

Etodolac

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Double-blind, parallel comparison of etodolac and indomethacin in patients with osteoarthritis of the knee. Author(s): Karbowski A. Source: Current Medical Research and Opinion. 1991; 12(5): 309-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1825972

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Double-blind, parallel-group evaluation of etodolac and naproxen in patients with acute sports injuries. Author(s): D'Hooghe M. Source: Clinical Therapeutics. 1992 July-August; 14(4): 507-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1388091

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Double-blind, placebo-controlled comparison of the safety and efficacy of orally administered etodolac and nabumetone in patients with active osteoarthritis of the knee. Author(s): Schnitzer TJ, Ballard IM, Constantine G, McDonald P. Source: Clinical Therapeutics. 1995 July-August; 17(4): 602-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8565024

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Double-blind, randomised, comparative trial of etodolac SR versus diclofenac in the treatment of osteoarthritis of the knee. Author(s): Liang TH, Hsu PN. Source: Current Medical Research and Opinion. 2003; 19(4): 336-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841927

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Economic and gastrointestinal safety comparisons of etodolac, nabumetone, and oxaprozin from insurance claims data from patients with arthritis. Author(s): Simon LS, Zhao SZ, Arguelles LM, Lefkowith JB, Dedhiya SD, Fort JG, Johnson KE. Source: Clinical Therapeutics. 1998 November-December; 20(6): 1218-35; Discussion 1192-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9916614

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Effect of etodolac in patients with moderate renal impairment compared with normal subjects. Author(s): Brater DC, Anderson SA, Brown-Cartwright D, Toto RD, Chen A, Jacob GB. Source: Clinical Pharmacology and Therapeutics. 1985 December; 38(6): 674-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2933206

Studies

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Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis. Author(s): Anaya JM, Fabre D, Bressolle F, Bologna C, Alric R, Cocciglio M, Dropsy R, Sany J. Source: The Journal of Rheumatology. 1994 February; 21(2): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8182625

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Effect on gastric and duodenal mucosal prostaglandins of repeated intake of therapeutic doses of naproxen and etodolac in rheumatoid arthritis. Author(s): Taha AS, McLaughlin S, Holland PJ, Kelly RW, Sturrock RD, Russell RI. Source: Annals of the Rheumatic Diseases. 1990 June; 49(6): 354-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2143369

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Effectiveness and safety of etodolac in treatment of rheumatoid arthritis: a multicentre two-months' open study. Author(s): Puccetti L, Soletti A, Petrini G, Remorini E, Zuccotti M, Bazzichi L, Ciompi ML. Source: Int J Clin Pharmacol Res. 1990; 10(6): 347-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2151575

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Effectiveness of etodolac ('Lodine') compared with naproxen in patients with acute gout. Author(s): Maccagno A, Di Giorgio E, Romanowicz A. Source: Current Medical Research and Opinion. 1991; 12(7): 423-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1838075

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Effects of etodolac on human chondrocytes cultivated in three dimensional culture. Author(s): Henrotin Y, Bassleer C, Reginster JY, Franchimont P. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 36-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2545406

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Effects of etodolac, a selective cyclooxygenase-2 inhibitor, on the expression of Ecadherin-catenin complexes in gastrointestinal cell lines. Author(s): Noda M, Tatsumi Y, Tomizawa M, Takama T, Mitsufuji S, Sugihara H, Kashima K, Hattori T. Source: Journal of Gastroenterology. 2002; 37(11): 896-904. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483244

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Effects of urinary metabolites of etodolac on diagnostic tests of bilirubin in urine. Author(s): Sho Y, Ishiodori T, Oketani M, Kubozono O, Nakamura A, Takeuchi A, Morino A, Arima T. Source: Arzneimittel-Forschung. 1999 July; 49(7): 572-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10442203

14

Etodolac

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Efficacy and safety of etodolac and naproxen in patients with osteoarthritis of the knee: a double-blind, placebo-controlled study. Author(s): Dore R, Ballard I, Constantine G, McDonald P. Source: Clinical Therapeutics. 1995 July-August; 17(4): 656-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8565029

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Efficacy and tolerability comparison of etodolac and piroxicam in the treatment of patients with osteoarthritis of the knee. Author(s): Astorga Paulsen G, Baigun S, Galvao de Figueiredo J, Gomes de Freitas G. Source: Current Medical Research and Opinion. 1991; 12(6): 401-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1828415

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

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Efficacy and tolerability of etodolac in the treatment of osteoarthritis. Author(s): Ciocci A. Source: Current Medical Research and Opinion. 1989; 11(7): 471-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2528441

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Efficacy of etodolac on gait in hip osteoarthritis as assessed by Bessou's locometer: a randomized, crossover, double-blind study versus placebo. Groupe de Recherche sur le Handicap de L'appareil Locomoteur. Author(s): Mejjad O, Favre S, Dujardin F, Thomine J, Le Loet X, Weber J. Source: Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society. 2000 May; 8(3): 230-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10806051

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Efficacy of transdermal nitroglycerin combined with etodolac for the treatment of chronic post-thoracotomy pain: an open-label prospective clinical trial. Author(s): Glantz L, Godovic G, Lekar M, Kramer M, Eidelman LA. Source: Journal of Pain and Symptom Management. 2004 March; 27(3): 277-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038339

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Endoscopic evaluation of etodolac and naproxen, and their relative effects on gastric and duodenal prostaglandins. Author(s): Russell RI. Source: Rheumatology International. 1990; 10 Suppl: 17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150567

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Enhanced clearance of leukemic lymphocytes in B-cell chronic lymphocytic leukemia with etodolac. Author(s): Nardella FA, LeFevre JA. Source: Blood. 2002 April 1; 99(7): 2625-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926185

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Etodolac (Lodine) in the treatment of osteoarthritis: recent studies. Author(s): Schnitzer TJ, Constantine G. Source: J Rheumatol Suppl. 1997 February; 47: 23-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035017

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Etodolac and the treatment of arthritis. Author(s): Scott DL. Source: Eur J Rheumatol Inflamm. 1990; 10(1): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146128

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Etodolac clinical pharmacokinetics. Author(s): Brocks DR, Jamali F. Source: Clinical Pharmacokinetics. 1994 April; 26(4): 259-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8013160

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Etodolac compared with aspirin: an endoscopic study of the gastrointestinal tracts of normal volunteers. Author(s): Lanza F, Panagides J, Salom IL. Source: The Journal of Rheumatology. 1986 April; 13(2): 299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2941572

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Etodolac in postsurgical pain: a double-blind dose-ranging efficacy study with aspirin and placebo. Author(s): Versichelen L, Bilsback P, Rolly G, Merlo M, Joubert L. Source: Int J Clin Pharmacol Ther Toxicol. 1982 May; 20(5): 236-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6212554

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Etodolac kinetics in the elderly. Author(s): Scatina J, Hicks D, Kraml M, Weidler D, Garg D, Sanda M. Source: Clinical Pharmacology and Therapeutics. 1986 May; 39(5): 550-3. Erratum In: Clin Pharmacol Ther 1986 September; 40(3): 358. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2938866

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Etodolac overdose. Author(s): Boldy DA, Hale KA, Vale JA. Source: Hum Toxicol. 1988 March; 7(2): 203-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2967796

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Etodolac preserves cartilage-specific phenotype in human chondrocytes: effects on type II collagen synthesis and associated mRNA levels. Author(s): Goldring MB, Sohbat E, Elwell JM, Chang JY. Source: Eur J Rheumatol Inflamm. 1990; 10(1): 10-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146129

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Etodolac selectively inhibits human prostaglandin G/H synthase 2 (PGHS-2) versus human PGHS-1. Author(s): Glaser K, Sung ML, O'Neill K, Belfast M, Hartman D, Carlson R, Kreft A, Kubrak D, Hsiao CL, Weichman B. Source: European Journal of Pharmacology. 1995 July 25; 281(1): 107-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8566109

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Etodolac therapy for osteoarthritis: a double-blind, placebo-controlled trial. Author(s): Williams PI, Hosie J, Scott DL. Source: Current Medical Research and Opinion. 1989; 11(7): 463-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2528440

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Etodolac versus diclofenac: double-blind cross-over study in rheumatoid arthritis. Author(s): Ciompi ML, Puccetti L, Bazzichi L, Remorini E, Marotta G. Source: Int J Clin Pharmacol Res. 1989; 9(3): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2526101

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Etodolac versus naproxen in rheumatoid arthritis: a double-blind crossover study. Author(s): Waltham-Weeks CD. Source: Current Medical Research and Opinion. 1987; 10(8): 540-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2960494

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Etodolac, a new nonsteroidal anti-inflammatory drug: gastrointestinal microbleeding and endoscopic studies. Author(s): Lanza FL, Arnold JD. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 5-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525983

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Etodolac, a novel antiinflammatory agent. The syntheses and biological evaluation of its metabolites. Author(s): Humber LG, Ferdinandi E, Demerson CA, Ahmed S, Shah U, Mobilio D, Sabatucci J, De Lange B, Labbadia F, Hughes P. Source: Journal of Medicinal Chemistry. 1988 September; 31(9): 1712-9. Erratum In: J Med Chem 1989 December; 32(12): 2582. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2970548

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Etodolac, aspirin, and gastrointestinal microbleeding. Author(s): Arnold JD, Mullane JF, Hayden DM, March L, Hart K, Perdomo CA, Fencik M, Berger AE. Source: Clinical Pharmacology and Therapeutics. 1984 May; 35(5): 716-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6232035

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

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Etodolac, aspirin, and placebo in patients with rheumatoid arthritis: a 12-week study. Author(s): Edwards W. Source: Clinical Therapeutics. 1983; 5(5): 495-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6225520

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Etodolac. A preliminary review of its pharmacodynamic activity and therapeutic use. Author(s): Lynch S, Brogden RN. Source: Drugs. 1986 April; 31(4): 288-300. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2940079

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Etodolac. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases and pain states. Author(s): Balfour JA, Buckley MM. Source: Drugs. 1991 August; 42(2): 274-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1717225

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Etodolac: analgesic effects in musculoskeletal and postoperative pain. Author(s): Pena M. Source: Rheumatology International. 1990; 10 Suppl: 9-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150571

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Etodolac: efficacy in osteoarthritis and effects on chondrocyte function. Author(s): Bacon PA. Source: Rheumatology International. 1990; 10 Suppl: 3-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150570

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Etodolac: the chemistry, pharmacology, metabolic disposition, and clinical profile of a novel anti-inflammatory pyranocarboxylic acid. Author(s): Humber LG. Source: Medicinal Research Reviews. 1987 January-March; 7(1): 1-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2951571

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Evaluation of etodolac in subjects with renal impairment. Author(s): Brater DC. Source: Eur J Rheumatol Inflamm. 1990; 10(1): 44-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146131

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Evaluation of the effectiveness and safety of etodolac in prolonged treatment of active osteoarthritis. Author(s): Puccetti L, Ciompi ML. Source: Int J Clin Pharmacol Res. 1991; 11(3): 143-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1839736

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Evaluation of the efficacy and comparative effects on gastric and duodenal mucosa of etodolac and naproxen in patients with rheumatoid arthritis using endoscopy. Author(s): Taha AS, McLaughlin S, Sturrock RD, Russell RI. Source: British Journal of Rheumatology. 1989 August; 28(4): 329-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525943

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Evaluation of the stereoselective metabolism of the chiral analgesic drug etodolac by high-performance liquid chromatography. Author(s): Becker-Scharfenkamp U, Blaschke G. Source: Journal of Chromatography. 1993 November 24; 621(2): 199-207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8294542

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Fulminant hepatic failure associated with etodolac use. Author(s): Mabee CL, Mabee SW, Baker PB, Kirkpatrick RB, Levine EJ. Source: The American Journal of Gastroenterology. 1995 April; 90(4): 659-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7717333

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Gas chromatography-mass spectrometry determination of etodolac in human plasma following single epicutaneous administration. Author(s): Giachetti C, Assandri A, Zanolo G, Brembilla E. Source: Biomedical Chromatography : Bmc. 1994 July-August; 8(4): 180-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7812122

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Gastric mucosal adaptation to etodolac and naproxen. Author(s): Lipscomb GR, Wallis N, Armstrong G, Goodman MJ, Rees WD. Source: Alimentary Pharmacology & Therapeutics. 1995 August; 9(4): 379-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8527613

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Gastrointestinal blood loss in arthritic patients receiving chronic dosing with etodolac and piroxicam. Author(s): Jallad NS, Sanda M, Salom IL, Perdomo CS, Garg DC, Mullane JF, Weidler DJ. Source: The American Journal of the Medical Sciences. 1986 November; 292(5): 272-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2946224

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Gastrointestinal microbleeding associated with the use of etodolac, ibuprofen, indomethacin, and naproxen in normal males. Author(s): Salom IL, Jacob G, Jallad N, Perdomo CA, Mullane JF, Weidler D. Source: Journal of Clinical Pharmacology. 1984 May-June; 24(5-6): 240-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6235249

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Global safety of etodolac: reports from worldwide postmarketing surveillance studies. Author(s): Serni U. Source: Rheumatology International. 1990; 10 Suppl: 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150568

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Identification of the etodolac metabolite, 4-ureidoetodolac, in mouse, rat, dog, and man. Author(s): Ferdinandi ES, Cochran D, Gedamke R. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1987 November-December; 15(6): 921-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2893722

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Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drug. Author(s): Cunha PD, Lord RS, Johnson ST, Wilker PR, Aster RH, Bougie DW. Source: Transfusion. 2000 June; 40(6): 663-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10864985

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In vitro effects of Etodolac and acetylsalicylic acid on human chondrocyte metabolism. Author(s): Henrotin Y, Bassleer C, Franchimont P. Source: Agents Actions. 1992 July; 36(3-4): 317-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1388320

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Influence of severity of chronic inflammatory joint disease on the pharmacokinetics of indomethacin and etodolac. Author(s): Pawlotsky Y, Le Dantec P, Jacquelinet C, Lapicque F, Goasguen J, Perdriger A, Veillard E, Guggenbuhl P, Netter P. Source: Rev Rhum Engl Ed. 1996 March; 63(3): 179-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8731235

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International experience with etodolac therapy for rheumatoid arthritis: an interim report of comparative efficacy. Author(s): Briancon D. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 63-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525985

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Isolation of an unknown metabolite of the non-steroidal anti-inflammatory drug etodolac and its identification as 5-hydroxy etodolac. Author(s): Strickmann DB, Blaschke G. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 July; 25(5-6): 977-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377082

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Large-scale open trials with etodolac (Lodine) in France: an assessment of safety. Author(s): Benhamou CL. Source: Rheumatology International. 1990; 10 Suppl: 29-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150569

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Low dose etodolac in rheumatoid arthritis: a review of early studies. Author(s): Spencer-Green G. Source: J Rheumatol Suppl. 1997 February; 47: 3-9; Discussion 48-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035014

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Meta-analysis of three double-blind comparative trials with sustained-release etodolac in the treatment of osteoarthritis of the knee. Author(s): Porzio F. Source: Rheumatology International. 1993; 13(2 Suppl): S19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8210920

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Meta-analysis of two double-blind comparative studies with the sustained-release form of etodolac in rheumatoid arthritis. Author(s): Porzio F. Source: Rheumatology International. 1993; 13(2 Suppl): S25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8210921

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Minimum effective dose of etodolac for the treatment of rheumatoid arthritis. Author(s): Jacob G, Messina M, Kennedy J, Epstein C, Sanda M, Mullane J. Source: Journal of Clinical Pharmacology. 1986 March; 26(3): 195-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2937811

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Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. I: Collagen synthesis. Author(s): Mauviel A, Redini F, Loyau G, Pujol JP. Source: Agents Actions. 1990 November; 31(3-4): 345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150740

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Modulation of extracellular matrix metabolism in rabbit articular chondrocytes and human rheumatoid synovial cells by the non-steroidal anti-inflammatory drug etodolac. II: Glycosaminoglycan synthesis. Author(s): Redini F, Mauviel A, Loyau G, Pujol JP. Source: Agents Actions. 1990 November; 31(3-4): 358-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150741

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Oral etodolac, a COX-2 inhibitor, reduces postoperative pain immediately after fasttrack cardiac surgery. Author(s): Koizuka S, Saito S, Obata H, Sasaki M, Nishikawa K, Takahashi K, Saito Y, Goto F. Source: Journal of Anesthesia. 2004; 18(1): 9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991469

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Pharmacokinetic and pharmacodynamic action of etodolac in patients after oral surgery. Author(s): Boni J, Korth-Bradley J, McGoldrick K, Appel A, Cooper S. Source: Journal of Clinical Pharmacology. 1999 July; 39(7): 729-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10392328

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Pharmacokinetic profile of etodolac in special populations. Author(s): Benet LZ. Source: Eur J Rheumatol Inflamm. 1994; 14(1): 15-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744123

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Pharmacokinetic study of etodolac after rectal administration; "in vitro" release kinetics. Author(s): Cadorniga R, Herrero R, Barcia E, Molina IT, Guitierrez JA, Fabregas JL, Martinez-Tobed A. Source: Eur J Drug Metab Pharmacokinet. 1991; Spec No 3: 389-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1840326

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Pharmacokinetics of etodolac in patients with stable juvenile rheumatoid arthritis. Author(s): Boni JP, Korth-Bradley JM, Martin P, Simcoe DK, Richards LS, Rennebohm R, Walson PD. Source: Clinical Therapeutics. 1999 October; 21(10): 1715-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10566567

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Pharmacokinetics of sustained-release etodolac. Author(s): Benet LZ. Source: Rheumatology International. 1993; 13(2 Suppl): S3-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8210922

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Profile of etodolac: pharmacokinetic evaluation in special populations. Author(s): Brater DC, Lasseter KC. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 25-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525981

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Recent clinical experience with etodolac in the treatment of osteoarthritis of the knee. Author(s): Platt PN. Source: Clinical Rheumatology. 1989 March; 8 Suppl 1: 54-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2525984

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Relief of dental surgery pain: a controlled 12-hour comparison of etodolac, aspirin, and placebo. Author(s): Nelson SL, Bergman SA. Source: Anesthesia Progress. 1985 July-August; 32(4): 151-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2934008

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

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Safety profile of etodolac in the elderly population. Author(s): Bacon PA. Source: Eur J Rheumatol Inflamm. 1994; 14(1): 19-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7744124

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Sensitive high-performance liquid chromatographic method for the determination of etodolac in serum. Author(s): Cosyns L, Spain M, Kraml M. Source: Journal of Pharmaceutical Sciences. 1983 March; 72(3): 275-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6221089

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Separation and identification of etodolac and its urinary phase I metabolites using capillary electrochromatography and on-line capillary electrochromatographyelectrospray ionisation mass spectrometry coupling. Author(s): Strickmann DB, Chankvetadz B, Blaschke G, Desiderio C, Fanali S. Source: J Chromatogr A. 2000 July 28; 887(1-2): 393-407. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961329

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Simultaneous determination of the phase II metabolites of the non steroidal antiinflammatory drug etodolac in human urine. Author(s): Berendes U, Blaschke G. Source: Enantiomer. 1996; 1(4-6): 415-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9676278

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Stereoselective binding of etodolac to human serum albumin. Author(s): Muller N, Lapicque F, Monot C, Payan E, Dropsy R, Netter P. Source: Chirality. 1992; 4(4): 240-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1389961

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Stereoselective disposition of etodolac enantiomers in synovial fluid. Author(s): Brocks DR, Jamali F, Russell AS. Source: Journal of Clinical Pharmacology. 1991 August; 31(8): 741-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1831817

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Stereoselective gas chromatographic analysis of etodolac enantiomers in human plasma and urine. Author(s): Singh NN, Jamali F, Pasutto FM, Coutts RT, Russell AS. Source: Journal of Chromatography. 1986 October 31; 382: 331-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2946709

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Etodolac

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The dissolution and bioavailability of etodolac from capsules exposed to conditions of high relative humidity and temperatures. Author(s): Dey M, Enever R, Kraml M, Prue DG, Smith D, Weierstall R. Source: Pharmaceutical Research. 1993 September; 10(9): 1295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8234166

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The effect of etodolac administration on renal function in patients with arthritis. Author(s): Shand DG, Epstein C, Kinberg-Calhoun J, Mullane JF, Sanda M. Source: Journal of Clinical Pharmacology. 1986 April; 26(4): 269-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2939116

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The effectiveness of 100 and 200 mg etodolac (Ultradol), aspirin, and placebo in patients with pain following oral surgery. Author(s): Hutton CE. Source: Oral Surg Oral Med Oral Pathol. 1983 December; 56(6): 575-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6228772

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The effectiveness of prophylactic etodolac on postendodontic pain. Author(s): Menke ER, Jackson CR, Bagby MD, Tracy TS. Source: Journal of Endodontics. 2000 December; 26(12): 712-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11471639

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The efficacy of etodolac for patients with pain following oral surgery. Author(s): Gaston GW, Mallow RD, Frank JE. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1984 June; 42(6): 362-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6232359

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The metabolic disposition of etodolac in rats, dogs, and man. Author(s): Cayen MN, Kraml M, Ferdinandi ES, Greselin E, Dvornik D. Source: Drug Metabolism Reviews. 1981; 12(2): 339-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6461537

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The pharmacokinetics of etodolac in serum and synovial fluid of patients with arthritis. Author(s): Kraml M, Hicks DR, McKean M, Panagides J, Furst D, Furst J. Source: Clinical Pharmacology and Therapeutics. 1988 May; 43(5): 571-6. Erratum In: Clin Pharmacol Ther 1988 August; 44(2): 201. Furst J[corrected to Furst D]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2966693

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The safety profile of sustained-release etodolac. Author(s): Schattenkirchner M. Source: Rheumatology International. 1993; 13(2 Suppl): S31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8210923

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The stereoselective pharmacokinetics of etodolac in young and elderly subjects, and after cholecystectomy. Author(s): Brocks DR, Jamali F, Russell AS, Skeith KJ. Source: Journal of Clinical Pharmacology. 1992 November; 32(11): 982-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1474171

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Tissue selective inhibition of prostaglandin biosynthesis by etodolac. Author(s): Dvornik DM. Source: J Rheumatol Suppl. 1997 February; 47: 40-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035019

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Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac. Author(s): Chen WS, Wei SJ, Liu JM, Hsiao M, Kou-Lin J, Yang WK. Source: International Journal of Cancer. Journal International Du Cancer. 2001 March 15; 91(6): 894-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11275997

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Twelve-week study of etodolac, aspirin, and placebo in patients with rheumatoid arthritis. Author(s): del Toro RA, Concepcion R. Source: Clinical Therapeutics. 1983; 5(4): 436-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6223699

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Worldwide experience with etodolac (Lodine) 300 mg b.i.d. in the treatment of osteoarthritis. Author(s): Bacon P. Source: Rheumatology International. 1993; 13(2 Suppl): S7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8210924

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CHAPTER 2. NUTRITION AND ETODOLAC Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and etodolac.

Finding Nutrition Studies on Etodolac 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.4 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 “etodolac” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

4 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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Etodolac

The following information is typical of that found when using the “Full IBIDS Database” to search for “etodolac” (or a synonym): •

A comparison of etodolac (Ultradol) with acetaminophen plus codeine (Tylenol #3) in controlling post-surgical pain in vasectomy patients. Author(s): Male Health Centres, Oakville, Ontario, Canada. Source: Casey, R Zadra, J Khonsari, H Curr-Med-Res-Opin. 1997; 13(10): 555-63 03007995

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A double-blind comparison of etodolac and piroxicam in the treatment of osteoarthritis. Source: Freitas, G G Curr-Med-Res-Opin. 1990; 12(4): 255-62 0300-7995

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A double-blind gastroscopic evaluation of the effects of etodolac and naproxen on the gastrointestinal mucosa of rheumatic patients. Author(s): Gastrointestinal Unit, L. Sacco Hospital, Milan, Italy. Source: Bianchi Porro, G Caruso, I Petrillo, M Montrone, F Ardizzone, S J-Intern-Med. 1991 January; 229(1): 5-8 0954-6820

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An overview of the efficacy of etodolac in arthritic disorders. Author(s): Department of Rheumatology, Medical School, University of Birmingham, England, U.K. Source: Bacon, P A Eur-J-Rheumatol-Inflamm. 1990; 10(1): 22-34 0140-1610

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Bioavailability and bioequivalence of two formulations of etodolac (tablets and suppositories). Author(s): Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad Complutense, Madrid, Spain. Source: Molina Martinez, I T Herrero, R Gutierrez, J A Iglesias, J M Fabregas, J L Martinez Tobed, A Cadorniga, R J-Pharm-Sci. 1993 February; 82(2): 211-3 0022-3549

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Clinical performance of etodolac in patients with osteoarthritis and rheumatoid arthritis. Author(s): Department of Rheumatology, University Hospital of Gent, Belgium. Source: Veys, E M Eur-J-Rheumatol-Inflamm. 1994; 14(1): 23-7 0140-1610

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Clinical response to etodolac in the management of pain. Author(s): National Institute of Rheumatology, Montevideo, Uruguay. Source: Mizraji, M Eur-J-Rheumatol-Inflamm. 1990; 10(1): 35-43 0140-1610

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Comparison of etodolac and diclofenac in osteoarthritis of the knee. Author(s): Rheumatology Department, University of Chile, Santiago. Source: Grisanti, A M Vaz, A A Samara, A M Clin-Ther. 1992 Nov-December; 14(6): 791800 0149-2918

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Comparison of the effects of etodolac SR and naproxen on gastro-intestinal blood loss. Author(s): Clinical Research Foundation, America, Lenexa, Kansas. Source: Leese, P Curr-Med-Res-Opin. 1992; 13(1): 13-20 0300-7995

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Double blind evaluation of the long-term effects of etodolac versus ibuprofen in patients with rheumatoid arthritis. Author(s): Department of Medicine, University of Louisville School of Medicine, KY 40202, USA. Source: Neustadt, D H J-Rheumatol-Suppl. 1997 February; 4717-22 0380-0903

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Double-blind comparison of etodolac and naproxen in the treatment of rheumatoid arthritis. Author(s): Rheumatology Clinic of Lisbon, Portugal. Source: de Queiros, M F Clin-Ther. 1991 Jan-February; 13(1): 38-46 0149-2918

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Double-blind, parallel comparison of etodolac and indomethacin in patients with osteoarthritis of the knee. Author(s): Klinik und Poliklinik fur Allgemeine Abteilung Orthopadie der WWU, Munster, Federal Republic of Germany. Source: Karbowski, A Curr-Med-Res-Opin. 1991; 12(5): 309-17 0300-7995

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Effect of etodolac on prostaglandin E2 biosynthesis, active oxygen generation and bradykinin formation. Author(s): Research Laboratories, Nippon Shinyaku Co. Ltd., Kyoto, Japan. Source: Inoue, K Motonaga, A Dainaka, J Nishimura, T Hashii, H Yamate, K Ueda, F Kimura, K Prostaglandins-Leukot-Essent-Fatty-Acids. 1994 December; 51(6): 457-62 0952-3278

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Effect of high-dose etodolac on renal function. Source: Brater, D C Brown Cartwright, D Anderson, S A Uaamnuichai, M ClinPharmacol-Ther. 1987 September; 42(3): 283-9 0009-9236

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Effect on gastric and duodenal mucosal prostaglandins of repeated intake of therapeutic doses of naproxen and etodolac in rheumatoid arthritis. Author(s): Gastroenterology Unit, Glasgow Royal Infirmary, Scotland. Source: Taha, A S McLaughlin, S Holland, P J Kelly, R W Sturrock, R D Russell, R I AnnRheum-Dis. 1990 June; 49(6): 354-8 0003-4967

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Effectiveness and safety of etodolac in treatment of rheumatoid arthritis: a multicentre two-months' open study. Author(s): First Institute of Medical Pathology, University of Pisa, Italy. Source: Puccetti, L Soletti, A Petrini, G Remorini, E Zuccotti, M Bazzichi, L Ciompi, M L Int-J-Clin-Pharmacol-Res. 1990; 10(6): 347-53 0251-1649

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Effectiveness of etodolac ('Lodine') compared with naproxen in patients with acute gout. Author(s): Service of Rheumatology, Hospital Frances, Universidad del Salvador, Buenos Aires, Argentina. Source: Maccagno, A Di Giorgio, E Romanowicz, A Curr-Med-Res-Opin. 1991; 12(7): 423-9 0300-7995

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Efficacy and tolerability comparison of etodolac and piroxicam in the treatment of patients with osteoarthritis of the knee. Author(s): Departmento de Reumatologia, Hospital Clinico de la Universidad de Chile, Santiago. Source: Astorga Paulsen, G Baigun, S Galvao de Figueiredo, J Gomes de Freitas, G CurrMed-Res-Opin. 1991; 12(6): 401-12 0300-7995

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Endoscopic evaluation of etodolac and naproxen, and their relative effects on gastric and duodenal prostaglandins. Author(s): Department of Gastroenterology, Royal Infirmary, Glasgow, UK. Source: Russell, R I Rheumatol-Int. 1990; 10 Suppl17-21 0172-8172

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Evaluation of etodolac in subjects with renal impairment. Author(s): Division of Clinical Pharmacology, Indiana University, School of Medicine, Indianapolis. Source: Brater, D C Eur-J-Rheumatol-Inflamm. 1990; 10(1): 44-55 0140-1610

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Evaluation of the effectiveness and safety of etodolac in prolonged treatment of active osteoarthritis. Author(s): 1st Institute of Medical Pathology, University of Pisa, Italy. Source: Puccetti, L Ciompi, M L Int-J-Clin-Pharmacol-Res. 1991; 11(3): 143-58 0251-1649

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Histopathologic evaluation of the effects of etodolac in established adjuvant arthritis in rats: evidence for reversal of joint damage. Source: Weichman, B M Chau, T T Rona, G Arthritis-Rheum. 1987 April; 30(4): 466-70 0004-3591

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International experience with etodolac therapy for rheumatoid arthritis: an interim report of comparative efficacy. Author(s): Centre Hospitalier d'Aix-les-Bains, France. Source: Briancon, D Clin-Rheumatol. 1989 March; 8 Suppl 163-72 0770-3198

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Large-scale open trials with etodolac (Lodine) in France: an assessment of safety. Author(s): Department of Rheumatology, Regional Hospital Center, Orleans, France. Source: Benhamou, C L Rheumatol-Int. 1990; 10 Suppl29-34 0172-8172

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Low dose etodolac in rheumatoid arthritis: a review of early studies. Author(s): Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA. Source: Spencer Green, G J-Rheumatol-Suppl. 1997 February; 473-9; discussion 48-50 0380-0903

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Pharmacokinetic study of etodolac after rectal administration; “in vitro” release kinetics. Author(s): Department of Pharmacy, Faculty of Pharmacy, University of Madrid, Spain. Source: Cadorniga, R Herrero, R Barcia, E Molina, I T Guitierrez, J A Fabregas, J L Martinez Tobed, A Eur-J-Drug-Metab-Pharmacokinet. 1991; Spec No 3389-96 0398-7639

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Recent clinical experience with etodolac in the treatment of osteoarthritis of the knee. Author(s): Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne, England, U.K. Source: Platt, P N Clin-Rheumatol. 1989 March; 8 Suppl 154-62 0770-3198

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Safety and efficacy of etodolac compared with piroxicam in patients with degenerative joint disease of the knee. Author(s): Department of Rheumatology, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom. Source: Dick, W C Bulstra, S Schardijn, G H Feenstra, R M Clin-Ther. 1992 Jul-August; 14(4): 517-26 0149-2918

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Safety profile of etodolac in the elderly population. Author(s): Faculty of Medicine, Department of Rheumatology, University of Birmingham, Edgbaston, UK. Source: Bacon, P A Eur-J-Rheumatol-Inflamm. 1994; 14(1): 19-22 0140-1610

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Temporal relationships of the anti-inflammatory effect of etodolac in the adjuvant arthritic rat. Author(s): Department of Biochemistry, Ayerst Laboratories Research, Inc., Princeton, New Jersey 08543-8000. Source: Lee, D K Chau, T T Weichman, B M Wooley, P H Proc-Soc-Exp-Biol-Med. 1988 March; 187(3): 273-7 0037-9727

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The dissolution and bioavailability of etodolac from capsules exposed to conditions of high relative humidity and temperatures. Author(s): Department of Pharmaceutical Sciences, Wyeth-Ayerst Research, Rouses Point, New York 12979. Source: Dey, M Enever, R Kraml, M Prue, D G Smith, D Weierstall, R Pharm-Res. 1993 September; 10(9): 1295-300 0724-8741

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The effect of etodolac on type II collagen-induced arthritis in mice. Author(s): Immunology Department, Ayerst Laboratories Research Inc., Princeton NJ 08540. Source: Wooley, P H Whalen, J D Zimmerman, J L Champion, T M Agents-Actions. 1987 August; 21(3-4): 244-6 0065-4299

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The effectiveness of prophylactic etodolac on postendodontic pain. Author(s): West Virginia University, Morgantown, USA. Source: Menke, E R Jackson, C R Bagby, M D Tracy, T S J-Endod. 2000 December; 26(12): 712-5 0099-2399

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The stereoselective pharmacokinetics of etodolac in young and elderly subjects, and after cholecystectomy. Author(s): Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada. Source: Brocks, D R Jamali, F Russell, A S Skeith, K J J-Clin-Pharmacol. 1992 November; 32(11): 982-9 0091-2700

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

•

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 etodolac; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Minerals Copper Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com

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

Comparative effects of long term treatment with etodolac, naproxen and ibuprofen on articular and bone changes associated with adjuvant arthritis in rats. Author(s): Martel RR, Klicius J, Metcalf G, Rona GA. Source: Agents Actions. 1984 October; 15(3-4): 403-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6240930

•

Disposition of etodolac, other anti-inflammatory pyranoindole-1-acetic acids and furobufen in normal and adjuvant arthritic rats. Author(s): Ferdinandi ES, Cayen MN, Pace-Asciak C. Source: The Journal of Pharmacology and Experimental Therapeutics. 1982 February; 220(2): 417-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6460096

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•

Effect of etodolac on articular and bone pathology associated with adjuvant arthritis in rats: a comparison with aspirin and naproxen. Author(s): Martel RR, Klicius J, Metcalf G. Source: Agents Actions. 1984 February; 14(2): 257-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6231845

•

Effect of etodolac on prostaglandin E2 biosynthesis, active oxygen generation and bradykinin formation. Author(s): Inoue K, Motonaga A, Dainaka J, Nishimura T, Hashii H, Yamate K, Ueda F, Kimura K. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1994 December; 51(6): 457-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7708812

•

Effect of high-dose etodolac on renal function. Author(s): Brater DC, Brown-Cartwright D, Anderson SA, Uaamnuichai M. Source: Clinical Pharmacology and Therapeutics. 1987 September; 42(3): 283-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2957139

•

Effect of the enantiomers of flurbiprofen, ibuprofen, and ketoprofen on intestinal permeability. Author(s): Davies NM, Wright MR, Russell AS, Jamali F. Source: Journal of Pharmaceutical Sciences. 1996 November; 85(11): 1170-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8923320

•

Histopathologic evaluation of the effects of etodolac in established adjuvant arthritis in rats: evidence for reversal of joint damage. Author(s): Weichman BM, Chau TT, Rona G. Source: Arthritis and Rheumatism. 1987 April; 30(4): 466-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2953342

•

Mechanism of anti-inflammatory action of etodolac. Author(s): Inoue K, Motonaga A, Nishimura T, Yokota M, Miki N, Fujisawa H, Ueda F, Shibata Y, Kimura K. Source: Arzneimittel-Forschung. 1991 March; 41(3): 235-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1714278

•

Temporal relationships of the anti-inflammatory effect of etodolac in the adjuvant arthritic rat. Author(s): Lee DK, Chau TT, Weichman BM, Wooley PH.

Alternative Medicine 35

Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1988 March; 187(3): 273-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2964641 •

The role of eicosanoids in the process of adaptation following massive bowel resection in the rat. Author(s): Kollman-Bauerly KA, Thomas DL, Adrian TE, Lien EL, Vanderhoof JA. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2001 September-October; 25(5): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11531219

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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

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

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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

The following is a specific Web list relating to etodolac; 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 Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com

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Etodolac

Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Etodolac Source: Healthnotes, Inc.; www.healthnotes.com Non-Steroidal Anti-Inflammatory Drugs Source: Healthnotes, Inc.; www.healthnotes.com Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) 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. PATENTS ON ETODOLAC 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.5 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 “etodolac” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on etodolac, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Etodolac By performing a patent search focusing on etodolac, 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

5Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on etodolac: •

3-(2-trialkylsilyloxy)ethyl-7-ethyl-1H-indoles and method for their preparation Inventor(s): Franco; Polastri (Milanino-MI, IT), Vincenzo; Giobbio (Turin, IT) Assignee(s): Teva Pharmaceutical Industries Ltd. (Petah Tiqva, IL) Patent Number: 5,599,946 Date filed: May 30, 1995 Abstract: The present invention relates to novel trialkylsilyloxy derivatives of 7ethyltryptophol useful in the preparation of etodolac, and methods of making them, and methods of using them to prepare etodolac. Excerpt(s): The present invention relates to novel trialkylsilyloxy derivatives of 7ethyltryptophol, i.e., 3-(2-trialkylsilyloxy)ethyl-7-ethyl-1H-indoles, useful in the preparation of etodolac, methods of preparing them, and methods of using them to prepare etodolac. The synthesis of etodolac described in these patents requires flash chromatographic purification of 7-ethyltryptophol in order to produce etodolac of a pharmaceutical quality (see U.S. Pat. No. 4,585,877, Example 3). However, the use of flash chromatography in industrial scale bulk synthetic reactions is very expensive, time consuming, and cannot be performed on an industrial scale, and is for this reason disfavored. It is therefore an object of the present invention to provide novel compounds useful for the efficient and cost-effective preparation of pharmaceutically acceptable etodolac on an industrial scale. In particular, it is an object of the invention to provide a method for making etodolac that does not require flash chromatography. Web site: http://www.delphion.com/details?pn=US05599946__

•

Antipyretic and analgesic methods of using optically pure R-etodolac Inventor(s): Gray; Nancy M. (Marlborough, MA), Wechter; William J. (Redlands, CA), Young; James W. (Palo Alto, CA) Assignee(s): Sepracor Inc. (Marlborough, MA) Patent Number: 5,561,151 Date filed: January 4, 1995 Abstract: Methods are disclosed utilizing optically pure R(-) etodolac for the treatment of pain, including but not limited to pain associated with toothaches, headaches, sprains, joint pain and surgical pain, for example dental pain and ophthalmic pain, while substantially reducing adverse effects which are associated with the administration of the racemic mixture of etodolac. The optically pure R(-) etodolac is also useful in treating pyrexia while substantially reducing the adverse effects associated with the administration of the racemic mixture of etodolac. Excerpt(s): This invention relates to novel compositions of matter containing optically pure R-etodolac. These compositions possess potent activity in treating pain including, but not limited to, pain associated with toothaches, headaches, sprains, joint pain and surgical pain, for example dental pain and ophthalmic pain, while substantially reducing adverse effects associated with the administration of the racemic mixture of etodolac including but not limited to gastrointestinal, renal and hepatic toxicities, as

Patents 39

well as leukopenia. Additionally, these novel compositions of matter containing optically pure R-etodolac are useful in treating or preventing pyrexia while substantially reducing the adverse effects associated with the administration of the racemic mixture of etodolac. Also disclosed are methods for treating the above-described conditions in a human while substantially reducing the adverse effects that are associated with the racemic mixture of etodolac, by administering the R-isomer of etodolac to said human. The active compound of the present compositions and methods is an optical isomer of the compound etodolac, also known as etodolic acid, which is described in Humber, L. G. et al., J. Med. Chem. 29: 871-874 (1986); Humber, L. G. Medicinal Research Reviews 7(1): 1-28 (1987); and U.S. Pat. No. 3,843,681 and German Patent No. DE 2,226,340, both to Demerson et al. Chemically, this R-isomer is (-) 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid. This isomer will hereinafter be referred to as R(-) etodolac. This term also includes the substantially optically pure and optically pure R(-) etodolac isomer. Etodolac, which is the subject of the present invention, is available commercially only as the 1:1 racemic mixture. That is, it is available only as a mixture of optical isomers, called enantiomers. The racemic mixture of etodolac is commercially available under the trade names ULTRADOL.RTM. and LODINE.RTM. by Ayerst Laboratories, New York. Web site: http://www.delphion.com/details?pn=US05561151__ •

Etodolac for inhibition of joint ankylosis Inventor(s): Wooley; Paul H. (Belle Mead, NJ) Assignee(s): American Home Products Corporation (Del.) (New York, NY) Patent Number: 4,710,511 Date filed: October 27, 1986 Abstract: A method is disclosed for inhibiting joint ankylosis for the treatment of arthritides by administering an effective amount of etodolac. Excerpt(s): This invention relates to a novel therapeutic use of 1,8-diethyl-1,3,4,9tetrahydropyrano[3,4-b]indole-1-acetic acid whose generic name is etodolac. More specifically this invention relates to a method of inhibiting joint ankylosis in mammals for the treatment of arthritides. It has now been found unexpectedly that etodolac, either in its free acid form or in its therapeutically acceptable salt form, is useful for inhibiting joint ankylosis in mammals for the treatment of arthritides. This finding, coupled with the fact that etodolac is a relatively safe drug, renders the method of this invention particularly useful and advantageous. Web site: http://www.delphion.com/details?pn=US04710511__

•

Extended release formulation of etodolac Inventor(s): Raghuvanshi; Rajeev S. (New Delhi, IN), Rampal; Ashok (Amritsar, IN), Sen; Himadri (Gurgaon, IN) Assignee(s): Ranbaxy Laboratories Limited (New Delhi, IN) Patent Number: 6,586,005 Date filed: August 25, 2000

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Abstract: A sustained release formulation of etodolac for once daily administration is described. Excerpt(s): The present invention relates to a sustained release formulation of etodolac for once daily administration. Etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano [3,4-b] indole-1-acetic acid or a therapeutically acceptable salt thereof) is disclosed in U.S. Pat. No. 3,939,178. It has been reported to have analgesic and anti-inflammatory properties. It has also been reported to be effective in the treatment of gout by lowering uric acid blood levels in humans (U.S. Pat. No. 4,663,345) and in the treatment of rheumatoid arthritis by lowering rheumatoid factor blood levels (U.S. Pat. No. 4,742,076). Etodolac is approved for the management of signs and symptoms of osteoarthritis, rheumatoid arthritis and for the management of pain. The conventional dosing regimen is 800 mg to 1200 mg given in 2-4 divided doses. This regimen can cause problems of compliance due to lack of patient convenience. It is well known to those skilled in the art that sustained release systems result in a decrease in frequency of administration thereby improving patient compliance. Furthermore, sustained released drug delivery systems produce constant therapeutic plasma levels of active ingredients as compared to fluctuations seen with multiple doses of a conventional formulation. However, development of a sustained release formulation of etodolac effective for 24 hours or suitable for once-aday administration poses problems due to a very low aqueous solubility of Etodolac which is pH independent below pH 3. The solubility then gradually increases with increasing pH up to 5 and then linearly increases with increasing pH up to 7. A thirtyfold difference between solubility at pH 5 to pH 7 has been observed. Web site: http://www.delphion.com/details?pn=US06586005__ •

Inhibition of bone resorption by etodolac Inventor(s): Hayward; Marshall A. (Lawrenceville, NJ) Assignee(s): American Home Products Corporation (New York, NY) Patent Number: 4,677,132 Date filed: March 12, 1986 Abstract: A method for modifying the balance between bone production and bone resorption in a host animal by administration of etodolac to inhibit bone resorption. Excerpt(s): This invention relates to a process for modifying the balance between bone production and bone resorption in a host animal, including man, and more specifically to the use of etodolac for the inhibition of bone resorption. Osteoporosis is a common condition in adults which is evidenced by a decrease in bone density throughout the body. In fact, both the bone mineral (calcium phosphate called "hydroxyapatite") and the matrix (major protein called "collagen") are slowly lost. This condition may begin to occur in humans as early as age 30. In general, the process is more rapid in women than in men. However, after age 80 there is no sex difference in the incidence of osteoporosis. In the course of 10 to 20 years of bone loss there may be symptoms of back pain and Xray evidence of deformation of the back bone. At older ages, the brittleness of the bones become evident by the ease in which the pelvis and femur fractures and the slowness of their subsequent healing. Osteoporosis is the most common cause of fractures in people over age 45. Although the cause of osteoporosis is poorly understood, it is believed that there is an imbalance between bone production and bone resorption (bone break-down). Bone remains a dynamic tissue throughout the life of an animal. That is, new bone is continuously being formed and old bone is continuously being resorbed. However, in

Patents 41

animals suffering from an osteoporotic condition, bone resorption exceeds bone formation. Web site: http://www.delphion.com/details?pn=US04677132__ •

Method of treating arthritis with etodolac Inventor(s): Martel; Rene (Candiac, CA) Assignee(s): American Home Products Corporation (New York, NY) Patent Number: 4,533,551 Date filed: February 17, 1984 Abstract: The effect of prolonged treatment with etodolac on the articular pathology associated with adjuvant arthritis in the rat has been compared to the effects produced by similar treatment with naproxen and ibuprofen. Drug effects were assessed by radiologic and histopathologic examinations. The effects on hindpaw edema, hindleg function, and body weight gain were also evaluated. Treatment was initiated on day 16 after adjuvant injection and continued for 28, 56 or 84 days. The degree of relapse which occurred during 28 days of non-treatment after dosage was stopped after 28 or 56 days of treatment was also assessed. Etodolac prevented the progression of the disease. Further, it appeared to diminish the severity of the articular lesions already present on day 16 before drug treatment began. All the parameters measured were improved and there was good agreement between the radiologic and histopathologic assessments of articular damage. The onset of drug activity was more rapid with etodolac than with the other drugs. By comparison naproxen and ibuprofen decreased edema, increased hindleg function and body weight gain and inhibited the progression of joint damage, but neither drug consistently decreased the magnitude of the articular damage present on day 16. With all three drugs there was less resurgence of disease symptoms when treatment was stopped after 56 days rather than 28 days of drug administration. Excerpt(s): Following treatment of adjuvant arthritic rats with the novel antiinflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1acetic acid, Ultradol.RTM.) there was less bone and articular damage than before the start of treatment. Thus after 28 days dosage etodolac appeared to produce some reversal of the articular pathology already present 16 days after the initiation of the disease. In the same experiment naproxen stopped the further progression of the joint pathology but did not reduce it, while aspirin merely prevented the damage from progressing to maximum intensity. For the present study the period of treatment has been extended (from day 16 up to day 100 after adjuvant) to ascertain whether a longer treatment period could reduce further the joint pathology. In addition the possibility of recurrence of the disease was explored by stopping treatment after different time intervals. The effects produced by etodolac have been compared to the results achieved by naproxen and ibuprofen under the same experimental conditions. The effects of the different treatment on joint damage were assessed by radiologic and histopathologic methods at the end of each experimental period. The evolution of the disease were also monitored by measuring hindleg volume, hindleg function and body weight periodically. Male inbred Wistar Lewis rats (180-220 g, initial weight) obtained from Charles River Breeding Laboratories, Boston, Mass., were injected intradermally in the distal third of the tail with 0.1 ml of Freund's Complete Adjuvant (FCA) composed of a fine suspension of killed and dried Mycobacterium butyricum (Difco) in liquid paraffin at a concentration of 5 mg/ml. The day of FCA injection was designated as day 0 of the experiments. On day 16 after administration of FCA, the volume of both hindpaws was

42

Etodolac

measured by mercury displacement according to the method of Hall, J. M. and Hallett, C.: A simple precise method for measuring rodent paw volume, J. Pharm. Pharmacol. 27:623 (1975). Web site: http://www.delphion.com/details?pn=US04533551__ •

Oral Formulations of S(+)-etodolac Inventor(s): Humber; Leslie G. (Brunswick, NJ), Reuter; Gerald L. (Plattsburgh, NY) Assignee(s): American Home Products Corporation (Madison, NJ) Patent Number: 5,958,445 Date filed: January 14, 1998 Abstract: This invention discloses organoleptically acceptable formulations containing non-solubilized S(+) 1,8-diethyl-1,3,4,9-tetrahydropyrano›3,4-b!indole-1-acetic acid, preferably with an acidic component, also known as S(+)etodolic acid or S(+)etodolac. Excerpt(s): Etodolac is a nonsteroidal antiinflamatory drug (NSAID) that exhibits antiinflammatory, analgesic, and antipyretic activities in animal models. Like that of other NSAIDs, the mechanism of etodolac is not completely understood, but is believed to be associated with an inhibition of prostaglandin biosynthesis. Etodolac is presently marketed by Wyeth-Ayerst Laboratories in the form of Lodine.RTM. tablets and capsules, which utilize a racemic mixture of etodolac. U.S. Pat. No. 3,939,178 (Demerson et al.) teaches and claims certain pyrano›3,4-B!indoles and thiopyrano›3,4-B!indoles which include the (.+-.) 1,8-diethyl-1,3,4,9-tetrahydropyrano›3,4-B!indole-1-acetic acid ingredient of Lodine.RTM. tablets and capsules. The Physicians' Desk Reference, 49 Edition, 1995, at page 2682, teaches that etodolac is insoluble in water but soluble in alcohols, chloroform, dimethyl sulfoxide and aqueous polyethylene glycol. Web site: http://www.delphion.com/details?pn=US05958445__

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Process for preparing 1,8-diethyl-1,3,4,9-tetrahydropyrano(3,4-b)-indole-1-acetic acid, etodolac Inventor(s): Demerson; Christopher A. (Plainsboro, NJ), Humber; Leslie G. (North Brunswick, NJ) Assignee(s): American Home Products Corporation (New York, NY) Patent Number: 4,585,877 Date filed: May 6, 1985 Abstract: A process for preparing 1,8-diethyl-1,3,4,9-tetrahydro[3,4-b]-indole-1-acetic acid (etodolac) is disclosed. Etodolac is a useful antiinflammatory and analgesic agent. Excerpt(s): This invention relates to the process for the preparation of 1,8-diethyl-1,3,4,9tetrahydropyrano[3,4-b]indole-1-acetic acid, also designated etodolac, disclosed as a potent antiinflammatory and analgesic compound in Demerson et al., U.S. Pat. No. 3,939,178. Preparations for pyrano[3,4-b]indoles have been previously described in Demerson et al., U.S. Pat. Nos. 3,939,178 and 4,012,417 and in Demerson et al., J. Med. Chem., 19, 391 (1976). Demerson et al., U.S. Pat. Nos. 3,939,178 and 4,012,417 disclose reaction of substituted tryptophols with keto ester to produce pyrano[3,4-b]indoles (see col. 9, lines 5 to 35). Etodolac is produced according to Example 477 of U.S. Pat. No.

Patents 43

4,012,417 by the reaction of 7-ethyltryptophol and the keto ester, ethyl propionylacetate, followed by alkaline hydrolysis. The 7-ethyltryptophol is produced by the reaction of 2ethylphenylhydrazine with 4-hydroxybutyraldehyde. Web site: http://www.delphion.com/details?pn=US04585877__ •

Process for the preparation of etodolac Inventor(s): Colombo; Paolo (Castellanza, IT), Vigano'; Enrico (Lurago D'Erba, IT) Assignee(s): A.M.S.A. Anonima Materie Sintetiche & Affini S.p.A. (IT) Patent Number: 6,066,741 Date filed: September 8, 1998 Abstract: Process for the preparation of etodolac, comprising the following steps:a) reacting 7-ethyl-tryptophol of formula (II) with methyl 3-oxo-pentanoate of formula (III) thereby obtaining methyl 1,8-diethyl-1,3,4,9-tetrahydropyrano [3,4-bis] indole-1-acetate of formula (IV) in an apolar solvent;b) hydrolyzing the compound of formula (IV) to etodolac (I),wherein step (a) is carried out at a temperatures of between -20.degree. C. and +50.degree. C. in the presence of a concentrated mineral acid, the molar ratio of the inorganic acid to 7-ethyl-tryptophol being comprised between 0.5 and 5. Excerpt(s): The present invention regards a process for the preparation of etodolac. The need is felt for having available an alternative process for the preparation of etodolac which does not involve the drawbacks presented by the processes of the known art. The applicant has now surprisingly found a process for the preparation of etodolac which does not present the drawbacks of the known art in so far it is conducted at lower temperatures than the reflux temperature of the solvent and in the absence of BF.sub.3.Et.sub.2 O. Web site: http://www.delphion.com/details?pn=US06066741__

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Process for the resolution of etodolac using glucamine derivatives Inventor(s): Adger; Brian Michael (Cambridge, GB), Andrews; John Francis Paul (Cambridge, GB), Baker; Helen Frances (Cambridge, GB), Dyer; Ulrich Conrad (Cambridge, GB), Woods; Martin (Cambridge, GB) Assignee(s): Chiroscience Limited (GB) Patent Number: 5,811,558 Date filed: December 6, 1996 Abstract: The subject invention pertains to a process for the resolution of etodolac comprising the use of the resolving agent glucamine or a N-(C.sub.1-4 alkyl)-glucamine. The subject invention also concerns a process for converting a single enantiomer of etodolac into the racemate. The method comprises forming all ester of the carboxylate function of the enantiomer and treating with an acid or base. Excerpt(s): This application is a 371 of PCT/GB 95/00857 filed on Apr. 11, 1995. This invention relates to etodolac, and in particular to novel enantiomeric salts thereof, a process for making those salts, and their use in the manufacture of medicaments. Etodolac is a chiral compound. It is a non-steroidal analgesic and anti-inflammatory agent which is marketed in racemic form. Its analgesic properties and preparation are

44

Etodolac

described in US-A-3843681 and sustained-release formulations containing it are described in EP-A-0309157. The existence of its meglumine and glucamine acid addition salts is disclosed in US-A-4748174, although the preparation and properties of these salts is not. Web site: http://www.delphion.com/details?pn=US05811558__ •

Sustained release etodolac Inventor(s): DeNeale; Richard J. (Willsboro, NY), Michelucci; John J. (Plattsburgh, NY), Sherman; Deborah M. (Plattsburgh, NY) Assignee(s): American Home Products Corporation (New York, NY) Patent Number: 4,966,768 Date filed: November 7, 1988 Abstract: A sustained release dosage form of etodolac is provided which is a tablet having as essential components etodolac, hydroxyproplymethylcellulose, ethylcellulose and a release rate modifying agent such as dibasic sodium phosphate, the hydroxyproplymethylcellulose having a hydroxypropoxyl content of about 7.0% to 8.6% by weight. Excerpt(s): This invention relates to a novel therapeutic dosage form of etodolac which provides drug plasma levels over a twenty-four hour period. More particularly, the sustained release dosage form is a tablet comprising as essential ingredients etodolac, hydroxypropylmethylcellulose, ethylcellulose and a release rate modifying agent such as dibasic sodium phosphate. The active agent of this invention, 1,8-diethyl-1,3,4,9tetrahydropyrano[3,4-b] indole-1-acetic acid or a therapeutically acceptable salt thereof, is disclosed in U.S. Pat. No. 3,939,178. This active agent, hereinafter designated by its generic name, etodolac, has been reported to have analgesic and anti-inflammatory properties. It has been further reported to be active in the treatment of adjuvant arthirtis, a model of inflammatory arthritis sensitive to treatment with nonsteroidal antiinflammatory drugs, in U.S. Pat. No. 4,533,551. Hydroxypropylmethylcellulose alone and in combination with ethylcellulose has been proposed as an ingredient in a sustained release formulation for twenty-four hour administration or therapeutic agents. See U.S. Pat. No. 4,369,172, issued Jan. 18, 1983 which describes dosage forms as a carrier base material a particular hydroxypropylmethylcellulose, i.e. having a hydroxypropoxyl content of 9-12 weight percent, a methoxyl content of 27-30 weight percent and a number average molecular weight of less than 50,000 with up to 30% by weight of the mixture of ethylcellulose. The patent describes comparative dissolution tests run with tablets made with this carrier base material and with a carrier base material made with a hydroxypropylmethylcellulose having a hydroxypropoxyl content of 8% by weight. The dissolution tests shown in Examples 1-4 of the patent indicate that the tablets made from the 8% hydroxypropxyl content material dissolve faster and release drug more rapidly than tablets made from 10.3% hydroxypropoxyl material. Web site: http://www.delphion.com/details?pn=US04966768__

Patents 45

•

Use of etodolac for the treatment of chronic lymphocytic leukemia Inventor(s): Adachi; Soichi (La Jolla, CA), Carson; Dennis A. (Del Mar, CA), Cottam; Howard B. (Escondido, CA), Leoni; Lorenzo M. (San Diego, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,545,034 Date filed: July 23, 1999 Abstract: A method of treating cancer is provided comprising administering an amount of etodolac to a subject afflicted with cancer that is effective to reduce the viability and/or to sensitize the cancer to an anti-cancer agent. Excerpt(s): Chronic lymphocytic leukemia (CLL) is the most common leukemia in the United States. CLL involves the cancerous proliferation of lymphocytes. It is most common among older adults; 90 percent of the cases are in people more than 50 years old. It occurs 1-3 times more often among men than among women. The onset of CLL tends to be insidious, with symptoms developing gradually. Because it involves an overproduction of mature, functional lymphocytes, persons with this disorder may survive for years. In contrast, in some, the disorder proceeds very rapidly, and requires immediate treatment. Currently, the adenine deoxynucleosides fludarabine (fludara) and 2-chlorodeoxyadenosine (2CdA) are the drugs of choice to treat the disease. However, clinical remissions are seldom induced, and patients eventually succumb from their leukemia. The number of nonsteroidal anti-inflammatory drugs (NSAIDs) has increased to the point where they warrant separate classification. In addition to aspirin, the NSAIDs available in the U.S. include meclofenamate sodium, oxyphenbutazone, phenylbutazone, indomethacin, piroxicam, sulindac and tolmetin for the treatment of arthritis; mefenamic acid and zomepirac for analgesia; and ibuprofen, fenoprofen and naproxen for both analgesia and arthritis. Ibuprofen, mefenamic acid and naproxen are used also for the management of dysmenorrhea. The clinical usefulness of NSAIDs is restricted by a number of adverse effects. Phenylbutazone has been implicated in hepatic necrosis and granulomatous hepatitis; and sulindac, indomethacin, ibuprofen and naproxen with hepatitis and cholestatic hepatitis. Transient increases in serum aminotransferases, especially alanine aminotransferase, have been reported. All of these drugs, including aspirin, inhibit cyclooxygenase, that in turn inhibits synthesis of prostaglandins, which help regulate glomerular filtration and renal sodium and water excretion. Thus, the NSAIDs can cause fluid retention and decrease sodium excretion, followed by hyperkalemia, oliguria and anuria. Moreover, all of these drugs can cause peptic ulceration. See, Remington's Pharmaceutical Sciences, Mack Pub. Co., Easton, Pa. (18th ed., 1990) at pages 1115-1122. Web site: http://www.delphion.com/details?pn=US06545034__

Patent Applications on Etodolac As of December 2000, U.S. patent applications are open to public viewing.6 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 etodolac: 6

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

46

•

Etodolac

Methods and compositions for the treatment of chronic lymphocytic leukemia Inventor(s): Nardella, Francis A.; (Scottsdale, AZ) Correspondence: Intellectual Property Group; Pillsbury Winthrop Llp; Suite 200; 11682 EL Camino Real; San Diego; CA; 92130; US Patent Application Number: 20030232874 Date filed: March 31, 2003 Abstract: The level of the leukemic lymphocytes in patients suffering from chronic lymphocytic leukemia (CLL) is reduced by the administration of certain indole or carbazole compounds, such as the nonsteroidal anti-inflammatory drug etodolac or related indole or carbazole compounds. Excerpt(s): The present invention relates to the use of indole derivatives characterized by having a 1,3,4,9-tetrahydropyrano [3,4-b]indole, 1,3,4,9-tetrahydrothiopyrano [3,4b]indole, 1,2,3,4-tetrahydro-4H carbazole or 2,3,4,9-tetrahydro-1H-carbazole nucleus, such as etodolac, in the treatment of chronic lymphocytic leukemia, and B-cell and T-cell lymphomas. Chronic lymphocytic leukemia (CLL) is a heterogeneous group of diseases characterized by different maturation states of the B-cells and T-cells, which are related to the aggressiveness of the disorder. Accordingly, CLL is commonly classified into separate categories, including B-cell chronic lymphocytic leukemia of classical and mixed-types, B-cell and T-cell prolymphocytic leukemia, hairy-cell leukemia and hairycell variant, splenic lymphoma with circulating villous lymphocytes, large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma syndrome and leukemic phases of malignant lymphomas of both B-cell and T-cell types. B-cell chronic lymphocytic leukemia (B-CLL) is characterized by proliferation and accumulation of Blymphocytes that appear morphologically mature but are biologically immature. B-CLL typically occurs in persons over 50 years of age. This disorder accounts for 30% of leukemias in Western countries, with 10,000 new cases being diagnosed annually in the United States alone. The disorder is characterized by proliferation of biologically immature lymphocytes (lymphocytosis), which typically express low levels of surface immunoglobulins, which upon organ infiltration cause lymph-node enlargement and hepato-splenomegaly. In the advanced stages of the disease, bone marrow occupation by the abnormal lymphocytes causes bone marrow failure, resulting in anemia and thrombocytopenia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Use of etodolac to treat hyperplasia Inventor(s): Carson, Dennis A.; (La Jolla, CA), Corr, Mary Patricia; (San Diego, CA), Leoni, Lorenzo M.; (San Diego, CA) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20040127431 Date filed: September 19, 2003 Abstract: The present invention provides a therapeutic method to treat non-malignant diseases characterized by the excessive tissue growth, e.g., hyperplastic diseases, comprising administering to a mammal (e.g., human) afflicted with excessive tissue growth, an effective amount of a derivative of an indole compound of formula

Patents 47

(I):formula (I): 1wherein R.sup.1 is lower alkyl, (hydroxy)lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, phenyl, benzyl or 2-thienyl; R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different and are each hydrogen or lower alkyl; each R.sup.6 is individually hydrogen, lower alkyl, hydroxy, (hydroxy)lower alkyl, lower alkoxy, benzyloxy, lower alkanoyloxy, nitro or halo, R.sup.7 is hydrogen, lower alkyl or lower alkenyl, X is oxy and thio, Y is carbonyl, --(CH.sub.2).sub.1-3--, --(C.sub.1C.sub.3)alkyl(CO)- --, or --(CH.sub.2).sub.1-3SO.sub.2--; Z is hydroxy, lower alkoxy, (C.sub.2-C.sub.4)acyloxy, --N(R.sup.8)(R.sup.9), phenylamino, (.omega.-(4pyridyl)(C.sub.2-C.sub.4 alkoxy), (.omega.-((R.sup.8)(R.sup.9- ) amino)(C.sub.2-C.sub.4 alkoxy), an amino acid ester of (.omega.-(HO)(C.sub.2-C.sub.4))alkoxy, -N(R.sup.8)CH(R.sup.8)CO.sub.2H, 1'-D-glucuronyloxy, --SO.sub.3H, --PO.sub.4H.sub.2, --N(NO)(OH), --SO.sub.2NH.sub.2, --PO(OH)(NH.sub.2), -OCH.sub.2CH.sub.2N(CH.sub.3).su- b.3.sup.+, or tetrazolyl; wherein R.sup.8 and R.sup.9 are each H, (C.sub.1-C.sub.3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R.sup.8), S or nonperoxide O; n is 0, 1, 2, or 3; wherein R.sup.8 and R.sup.9 are each H, (C.sub.1-C.sub.3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R.sup.8), S or nonperoxide O; each alkyl or phenyl group of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7 and Z is optionally substituted with 1, 2, or 3 (C.sub.1-C.sub.4)alkyl groups; or a pharmaceutically acceptable salt thereof. Excerpt(s): This application claims priority of U.S. provisional patent application Serial No. 60/412,193, filed Sep. 19, 2002, which is incorporated by reference herein. Hyperplastic diseases are non-malignant conditions that represent an unmet medical need. Typically, these diseases are characterized by the uncontrolled growth of cells. In many patients these cells are not malignant and the hyperplastic cells do not lead to the development of cancer. Thus, the hyperplastic cells are not treated with the conventional chemotherapeutic agents useful against malignant diseases. One example of a hyperplastic disease is benign prostatic hypertrophy (BPH). This disease is characterized by the abnormal growth of the prostate. Substantial data currently exist showing that prostate volume increases with age in a measurable group of middle-aged and older men, following a post-pubertal plateau. In addition, the incidence and prevalence of prostate disease increase with age, and are very high in elderly men (>40%). Other nonmalignant hyperplastic diseases include, but are not limited to fibroplastic dysplasia of the breast, fibroplastic growths in the uterus or cervix, and gastric hyperplastic polyposis. In many patients, hyperplastic diseases do not lead to the development of cancer, and are not treated with the conventional chemotherapeutic agents used against malignant diseases. 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 etodolac, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “etodolac” (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 etodolac.

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You can also use this procedure to view pending patent applications concerning etodolac. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

49

CHAPTER 5. PERIODICALS AND NEWS ON ETODOLAC Overview In this chapter, we suggest a number of news sources and present various periodicals that cover etodolac.

News Services and Press Releases One of the simplest ways of tracking press releases on etodolac 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 “etodolac” (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 etodolac. 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 “etodolac” (or synonyms). The following was recently listed in this archive for etodolac: •

Lederle issues "Dear Doctor" letter concerning etodolac recall Source: Reuters Industry Breifing Date: October 11, 2000

•

ESI Lederle recalls etodolac capsules on fears of contamination Source: Reuters Industry Breifing Date: October 05, 2000

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•

Roberts acquires rights to etodolac in UK and Ireland Source: Reuters Medical News Date: March 10, 1999

•

FDA Approves Watson's Etodolac Capsules Source: Reuters Medical News Date: December 30, 1997

•

FDA Approves Mylan's Etodolac Capsules Source: Reuters Medical News Date: May 19, 1997

•

Roberts Licenses Wyeth Laboratories' Lodine In U.K., Ireland Source: Reuters Medical News Date: January 07, 1997 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 “etodolac” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “etodolac” (or synonyms). If you know the name of a company that is relevant to etodolac, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for

Periodicals and News

51

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 “etodolac” (or synonyms).

Academic Periodicals covering Etodolac Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to etodolac. In addition to these sources, you can search for articles covering etodolac 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 6. 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 etodolac. 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 nonprofit 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 etodolac. 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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Etodolac

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to etodolac: Anti-inflammatory Drugs, Nonsteroidal •

Systemic - U.S. Brands: Actron; Advil; Advil Caplets; Advil, Children's; Aleve; Anaprox; Anaprox DS; Ansaid; Bayer Select Ibuprofen Pain Relief Formula Caplets; Cataflam; Clinoril; Cotylbutazone; Cramp End; Daypro; Dolgesic; Dolobid; EC-Naprosyn; Excedrin IB; Excedrin IB Caplets; Feldene; Genpril; Genpril Caplets; Haltran; Ibifon 600 Caplets; Ibren; Ibu; Ibu-200; Ibu-4; Ibu-6; Ibu8; Ibuprin; Ibuprohm; Ibuprohm Caplets; Ibu-Tab; Indocin; Indocin SR; Lodine; Lodine XL; Meclomen; Medipren; Medipren Caplets; Midol IB; Mobic; Motrin; Motrin Chewables; Motrin, Children's; Motrin, Children's Oral Drops; Motrin, Junior Strength Caplets; Motrin-IB; Motrin-IB Caplets; Nalfon; Nalfon 200; Naprelan; Naprosyn; Nuprin; Nuprin Caplets; Orudis; Orudis KT; Oruvail; Pamprin-IB; Ponstel; Q-Profen; Relafen; Rufen; Tolectin 200; Tolectin 600; Tolectin DS; Trendar; Voltaren http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202743.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Medications

55

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.

57

APPENDICES

59

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 Institute7: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

7

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

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

•

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

•

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

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

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

•

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

•

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

•

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

•

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

•

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

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.8 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:9 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

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

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

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

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

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

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

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

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

8

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). 9 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 Gateway10 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.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “etodolac” (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 416 2 992 2 1 1413

HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 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.14 Simply search by “etodolac” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

10

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

11

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). 12 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 13 14

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 Biologists15 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.16 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.17 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/.

15 Adapted 16

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. 17 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 etodolac 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 etodolac. 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 etodolac. 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 “etodolac”:

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Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Carpal Tunnel Syndrome http://www.nlm.nih.gov/medlineplus/carpaltunnelsyndrome.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Medicines http://www.nlm.nih.gov/medlineplus/medicines.html Sprains and Strains http://www.nlm.nih.gov/medlineplus/sprainsandstrains.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 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 etodolac. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

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

•

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

•

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

•

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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to etodolac. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with etodolac. 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 etodolac. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “etodolac” (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 “etodolac”. 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 “etodolac” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “etodolac” (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.18

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

18

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)19: •

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

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

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

19

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

•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

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

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

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

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

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

•

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

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

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

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

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

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

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

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

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

•

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

•

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

•

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

•

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

•

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

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

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

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

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

•

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

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

75

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

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

•

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

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

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

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

77

ETODOLAC DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] 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] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is

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produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Ampulla: A sac-like enlargement of a canal or duct. [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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angina: Chest pain that originates in the heart. [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] 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] Ankylosis: Fixation and immobility of a joint. [NIH]

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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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Anus: The opening of the rectum to the outside of the body. [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] 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] 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] Articular: Of or pertaining to a joint. [EU] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied

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in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] 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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Bladder: The organ that stores urine. [NIH]

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Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [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] Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH]

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Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] 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] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [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] 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] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Chondrocytes: Polymorphic cells that form cartilage. [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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [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] 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] 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]

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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] 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] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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

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theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]

Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [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]

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Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] 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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during cryopreservation. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids,

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prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] 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] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [NIH] Dysmenorrhea: Painful menstruation. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] 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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from

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intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Etodolac: A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and in the alleviation of postoperative pain. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fenoprofen: An anti-inflammatory analgesic and antipyretic highly bound to plasma proteins. It is pharmacologically similar to aspirin, but causes less gastrointestinal bleeding. [NIH]

Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flatus: Gas passed through the rectum. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting carbonic anhydrase. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored

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in the gallbladder. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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]

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] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] 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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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

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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] 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] 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] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepato-splenomegaly: Enlargement of the liver and spleen. [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] 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] 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] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side

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effect of some anticancer drugs. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] 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] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [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] 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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a

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net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [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] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune

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system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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] Mefenamic Acid: A non-steroidal anti-inflammatory agent with analgesic, antiinflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase. [NIH] Meglumine: 1-Deoxy-1-(methylamino)-D-glucitol. A derivative of sorbitol in which the hydroxyl group in position 1 is replaced by a methylamino group. Often used in conjunction with iodinated organic compounds as contrast medium. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] 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] 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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an

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inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] 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] 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] Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties. [NIH] 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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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] 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] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the

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acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] 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] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] 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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Ophthalmic: Pertaining to the eye. [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] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal

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osteoporosis and age-related (or senile) osteoporosis. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH]

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Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [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] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] 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] 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] 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] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma 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] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation

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of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

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] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] 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] 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] 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] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by

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thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [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] 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] 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] Pyrexia: A fever, or a febrile condition; abnormal elevation of the body temperature. [EU] 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] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [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] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [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] 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] 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] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH]

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Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] 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] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which 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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] 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] 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] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of

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old age. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

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] 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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [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] Sperm: The fecundating fluid of the male. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between

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the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [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] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

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] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracotomy: Surgical incision into the chest wall. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] 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]

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] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolmetin: An anti-inflammatory antipyretic and analgesic similar in mode of action to indomethacin. It has been proposed as an antirheumatic agent. [NIH]

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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] 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] 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] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [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] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]

Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

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Venous: Of or pertaining to the veins. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] 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]

Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]

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INDEX A Acetaminophen, 6, 28, 77 Acetic Acids, 33, 77 Acute renal, 77, 89 Acyl, 10, 77 Adaptability, 77, 82 Adaptation, 19, 35, 77 Adenine, 45, 77 Adjustment, 77 Adjuvant, 30, 33, 34, 41, 44, 77, 88 Adverse Effect, 38, 45, 77, 100 Aerobic, 77, 93 Affinity, 77, 100 Aggressiveness, 46, 77 Alanine, 45, 77 Albumin, 6, 7, 10, 78, 96, 101 Algorithms, 78, 80 Alkaline, 43, 78, 81 Alternative medicine, 50, 78 Alveolar Process, 78, 99 Amino acid, 47, 77, 78, 79, 85, 88, 89, 92, 95, 97, 98, 101, 102 Ampulla, 78, 86 Analgesic, 17, 18, 38, 40, 42, 43, 44, 77, 78, 82, 85, 87, 90, 91, 92, 93, 101 Analog, 78, 93 Anatomical, 78, 90 Anemia, 19, 46, 78, 93 Angina, 78, 94 Angiotensinogen, 78, 99 Animal model, 42, 78 Anions, 78, 91, 100 Ankylosis, 39, 78 Antibodies, 79, 88, 90, 92, 96 Antibody, 77, 79, 83, 88, 90, 98 Anticoagulant, 79, 98 Antigen, 77, 79, 83, 89, 90, 98 Anti-Inflammatory Agents, 79 Antimetabolite, 79, 92 Antineoplastic, 79, 92 Antipyretic, 38, 42, 77, 79, 85, 87, 91, 92, 93, 101 Anus, 79, 83, 98 Apoptosis, 4, 79, 82 Aqueous, 40, 42, 79, 84 Arachidonic Acid, 79, 86, 97 Arterial, 79, 94, 98 Arteries, 79, 81, 84, 93, 101

Arterioles, 79, 81 Articular, 21, 33, 34, 41, 79, 94 Aspirin, 9, 15, 17, 22, 24, 25, 34, 41, 45, 79, 87 Assay, 8, 80, 98 Astringents, 80, 92 Autoimmune disease, 5, 80 B Back Pain, 40, 80 Bacteria, 77, 79, 80, 84, 88, 93 Bacterial Physiology, 77, 80 Bacterium, 80, 84, 89 Basement Membrane, 80, 87 Benign, 47, 80 Bile, 80, 86, 87, 91 Bilirubin, 13, 78, 80 Binding Sites, 7, 80 Bioavailability, 8, 24, 28, 31, 80 Biochemical, 5, 79, 80, 94 Biosynthesis, 9, 25, 29, 34, 42, 79, 80 Biotechnology, 5, 50, 61, 80 Biotransformation, 10, 80 Bladder, 80, 83, 97, 102 Blood Coagulation, 81, 101 Blood Platelets, 81, 101 Blood pressure, 81, 93, 100 Blood vessel, 81, 88, 89, 91, 100, 102 Body Fluids, 81, 100 Bone Density, 40, 81 Bone Marrow, 46, 81, 91, 93 Bone Resorption, 40, 81, 87 Bowel, 35, 81, 90, 101 Bradykinin, 29, 34, 81, 91, 96 Buccal, 81, 91 C Calcium, 40, 81, 83 Calculi, 81, 88 Capillary, 8, 23, 81, 103 Capillary Permeability, 81 Capsules, 24, 31, 42, 49, 50, 82, 86, 88 Carbon Dioxide, 81, 82, 99 Carcinogenic, 82, 90 Cardiac, 21, 82, 93 Carrier Proteins, 82, 96, 98 Caspase, 4, 82 Cell, 5, 13, 15, 46, 77, 79, 80, 82, 83, 84, 86, 87, 90, 93, 94, 98, 99, 101, 103 Cell Death, 5, 79, 82, 94

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Cell Respiration, 82, 93, 99 Cell Survival, 5, 82 Central Nervous System, 78, 82, 93 Cervix, 47, 82 Character, 82, 85 Chemotherapeutic agent, 47, 82 Chest wall, 82, 101 Chloroform, 42, 82 Cholecystectomy, 25, 31, 82 Chondrocytes, 13, 16, 21, 82 Chromatin, 79, 82 Chronic, 4, 14, 15, 19, 20, 45, 46, 80, 82, 90 Chronic lymphocytic leukemia, 4, 15, 45, 46, 82 Clinical trial, 4, 14, 61, 82, 84, 86, 98 Cloning, 80, 82 Codeine, 6, 28, 82 Colitis, 7, 83 Collagen, 16, 21, 31, 40, 78, 80, 83, 88, 97 Colloidal, 78, 83, 100 Colon, 25, 83, 91 Complement, 83, 96 Complementary and alternative medicine, 33, 36, 83 Complementary medicine, 33, 83 Compliance, 40, 83 Computational Biology, 61, 83 Concomitant, 4, 10, 84 Cone, 84, 101 Conjugation, 80, 84 Connective Tissue, 81, 83, 84, 85, 88, 99 Consciousness, 78, 84, 85 Contamination, 49, 84, 89 Contraindications, ii, 84 Contrast medium, 84, 92 Controlled study, 14, 84 Coronary, 84, 93, 94 Coronary Thrombosis, 84, 93 Cortisol, 78, 84 Cryopreservation, 84, 85 Curative, 84, 101 Cutaneous, 84, 91 Cytoplasm, 79, 84, 85, 86 Cytoskeleton, 5, 85 D Degenerative, 11, 14, 17, 22, 30, 85, 89, 94 Deletion, 79, 85 Density, 81, 85, 97 Dermis, 85, 102 Deuterium, 85, 89 Diagnostic procedure, 37, 50, 85 Diclofenac, 7, 9, 11, 12, 16, 28, 85

Diclofenac Sodium, 85 Diffusion, 81, 85, 90 Digestion, 80, 81, 85, 90, 91, 95, 100 Dilation, 81, 85 Dilator, 85, 94 Dimethyl, 42, 85 Dimethyl Sulfoxide, 42, 85 Direct, iii, 53, 85, 98 Disposition, 8, 10, 18, 19, 23, 24, 33, 85 Dissociation, 77, 85, 91 Distal, 41, 85 Dosage Forms, 44, 85 Double-blind, 6, 11, 12, 14, 15, 16, 20, 21, 28, 29, 86 Drug Delivery Systems, 40, 86 Drug Interactions, 54, 86 Duodenum, 80, 86, 95, 101 Dysmenorrhea, 45, 86, 94, 96 Dysplasia, 47, 86 E Edema, 41, 86 Efficacy, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 18, 20, 22, 24, 28, 29, 30, 86 Effusion, 86, 92 Eicosanoids, 35, 86 Elastin, 83, 86 Electrolyte, 86, 100 Electrons, 86, 90, 91, 95 Endogenous, 86 Endoscope, 86 Endoscopic, 4, 7, 14, 15, 16, 29, 86 Endoscopy, 6, 18, 86 Endotoxins, 83, 86, 91 Enterohepatic, 86, 101 Enterohepatic Circulation, 86, 101 Environmental Health, 60, 62, 87 Enzymatic, 78, 81, 83, 87, 89 Enzyme, 82, 87, 88, 90, 92, 95, 96, 98, 99, 101, 103 Erythrocytes, 78, 81, 87, 98 Esophagus, 87, 95, 98, 101 Exogenous, 80, 86, 87 Expiration, 87, 99 Extracellular, 21, 84, 87, 100 Extracellular Matrix, 21, 84, 87 Extracellular Space, 87 Extraction, 11, 87 F Family Planning, 61, 87 Fat, 79, 81, 87, 91, 99, 100, 101 Febrile, 87, 98 Femur, 40, 87

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Fenoprofen, 45, 87 Fetus, 87, 102 Filtration, 45, 87 Flatus, 87, 88 Fludarabine, 45, 87 Flurbiprofen, 34, 87 Fold, 40, 87 G Gait, 14, 87 Gallbladder, 82, 87 Gas, 19, 23, 82, 85, 87, 88, 89, 101 Gastric, 7, 13, 14, 18, 19, 29, 47, 85, 88, 89, 93, 94, 95, 98 Gastric Acid, 88, 93, 94 Gastric Juices, 88, 95 Gastrin, 88, 89 Gastrointestinal, 3, 6, 7, 12, 13, 15, 16, 17, 19, 28, 38, 81, 87, 88, 96, 98, 101 Gastrointestinal tract, 15, 88 Gelatin, 88, 101 Gene, 80, 88 Genotype, 88, 96 Gland, 88, 97, 99, 101 Glomerular, 45, 88 Glomerulus, 88 Glutathione Peroxidase, 88, 99 Glycine, 78, 88, 94 Gout, 13, 29, 40, 88, 94 Governing Board, 88, 97 H Half-Life, 88, 96 Haptens, 77, 88, 98 Heme, 80, 88 Hemoglobin, 78, 87, 88 Hemolytic, 19, 89 Hepatic, 18, 38, 45, 78, 89 Hepatitis, 45, 89 Hepatitis A, 45, 89 Hepatocytes, 89 Hepato-splenomegaly, 46, 89 Hepatovirus, 89 Histamine, 89, 98 Histology, 89, 95 Hormone, 5, 84, 86, 88, 89, 99 Hydrogen, 47, 85, 88, 89, 93, 95, 96, 98 Hydrolysis, 43, 80, 89, 97 Hydroxylysine, 83, 89 Hydroxyproline, 78, 83, 89 Hyperplasia, 46, 89 Hypersensitivity, 89, 99 Hypertrophy, 47, 89 Hyperuricemia, 88, 89

I Ibuprofen, 4, 6, 7, 10, 19, 28, 33, 34, 41, 45, 54, 90, 91 Imidazole, 89, 90, 98 Immune response, 77, 79, 80, 88, 90, 101 Immune system, 90, 92, 103 Immunogenic, 90, 98 Immunoglobulins, 46, 90, 96 Immunology, 31, 77, 90 Immunosuppressant, 90, 92 Impairment, 12, 18, 29, 90 In vitro, 10, 20, 22, 30, 90 In vivo, 90, 101 Incision, 90, 101 Indomethacin, 7, 9, 12, 19, 20, 29, 45, 90, 101 Infarction, 84, 90, 93 Infection, 90, 91, 92, 99, 103 Infiltration, 46, 90 Inflammation, 9, 78, 79, 83, 85, 89, 90, 96, 99, 100 Initiation, 41, 90 Inorganic, 43, 90 Intestinal, 9, 28, 34, 90 Intestine, 81, 86, 90, 91 Intracellular, 90, 99 Ionization, 8, 90 Ions, 85, 86, 89, 91 K Kallidin, 81, 91 Kb, 60, 91 Keto, 42, 91 Ketoprofen, 34, 91 Kidney stone, 91, 102 Kinetics, 15, 22, 30, 91 L Large Intestine, 90, 91, 98, 100 Lesion, 91, 102 Leukemia, 45, 46, 91 Leukocytes, 81, 90, 91 Leukopenia, 39, 91 Ligament, 91, 97 Lipid, 81, 91 Liver, 25, 77, 78, 79, 80, 86, 87, 89, 91 Localized, 90, 91, 102 Lumbar, 9, 80, 91 Lupus, 66, 91 Lymph, 46, 91 Lymphatic, 90, 91, 100 Lymphatic system, 91, 100 Lymphocyte, 4, 79, 91 Lymphocytic, 46, 92

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Lymphocytosis, 46, 92 Lymphoid, 79, 92 Lymphoma, 46, 92 Lymphoproliferative, 4, 92 M Malignant, 5, 46, 47, 79, 92, 93 Malignant tumor, 92, 93 Malnutrition, 78, 92 Mandible, 78, 92, 99 Mediate, 92, 98 Medicament, 92, 101 MEDLINE, 61, 92 Mefenamic Acid, 45, 92 Meglumine, 44, 92 Membrane, 83, 92, 93, 94, 95, 97, 101 Menstruation, 86, 92 Mental, iv, 4, 60, 62, 85, 92, 99 Mercury, 42, 92 Metabolic disorder, 88, 92 Metabolite, 19, 20, 80, 85, 92 Metastasis, 25, 92 Methionine, 85, 92 Methotrexate, 10, 13, 92 MI, 38, 75, 93 Microbe, 93, 102 Microbiology, 77, 93 Microorganism, 93, 103 Milliliter, 81, 93 Misoprostol, 4, 93 Mitochondria, 5, 93 Mitochondrial Swelling, 93, 94 Mitosis, 79, 93 Modification, 78, 93 Molecular, 44, 61, 63, 80, 84, 91, 93 Molecule, 79, 80, 81, 83, 85, 89, 93, 95, 98 Monitor, 93, 94 Morphine, 82, 93 Motility, 90, 93 Mucosa, 6, 7, 18, 28, 91, 93 Multiple Myeloma, 5, 93 Myocardium, 93 N Naproxen, 5, 6, 7, 9, 11, 12, 13, 14, 16, 18, 19, 28, 29, 33, 34, 41, 45, 93 Nausea, 86, 94 Necrosis, 45, 79, 90, 93, 94 Neoplastic, 92, 94 Neurotransmitter, 78, 81, 88, 89, 94, 101 Nitroglycerin, 14, 94 Nuclear, 5, 84, 86, 94 Nucleus, 46, 79, 82, 84, 85, 94, 98

O Ointments, 86, 94, 95 Oliguria, 45, 94 Omeprazole, 4, 94 On-line, 23, 75, 94 Ophthalmic, 38, 94 Osmotic, 78, 93, 94, 100 Osteoarthritis, 5, 6, 8, 9, 11, 12, 14, 15, 16, 18, 20, 22, 25, 28, 29, 30, 36, 40, 87, 91, 94, 96 Osteoporosis, 40, 94 Overdose, 16, 95 Oxidation, 80, 88, 95 Oxidation-Reduction, 80, 95 Oxygen Consumption, 95, 99 Oxytocic, 93, 95 P Palliative, 95, 101 Paraffin, 41, 95 Parietal, 94, 95 Patch, 95, 102 Pathogenesis, 4, 95 Pathologic, 79, 84, 89, 95, 99 Pathologic Processes, 79, 95 Patient Compliance, 40, 95 Pelvic, 95, 97 Pelvis, 40, 91, 95, 102 Pepsin, 93, 95 Peptic, 45, 95 Peptic Ulcer, 45, 95 Peptide, 78, 95, 97, 98 Periodontal disease, 87, 95, 96 Petroleum, 95, 96 PH, 34, 81, 96 Pharmaceutical Solutions, 86, 96 Pharmacodynamic, 17, 21, 96 Pharmacokinetic, 8, 21, 22, 30, 96 Pharmacologic, 5, 10, 88, 96, 102 Phenotype, 16, 96 Phenyl, 47, 96 Phosphorus, 81, 96 Physiologic, 80, 88, 92, 96, 98, 99 Pigment, 80, 96 Piroxicam, 6, 10, 11, 14, 19, 22, 28, 29, 30, 45, 96 Plasma, 19, 23, 40, 44, 77, 78, 79, 87, 88, 93, 96, 99, 100 Plasma cells, 79, 93, 96 Plasma protein, 78, 87, 96, 100 Pneumonia, 84, 96 Poisoning, 92, 94, 96 Polyethylene, 42, 97

109

Polypeptide, 78, 83, 97, 103 Polyposis, 47, 97 Posterior, 80, 97 Postmenopausal, 94, 97 Postoperative, 17, 21, 87, 96, 97 Practice Guidelines, 62, 97 Prevalence, 47, 97 Probe, 5, 97 Progression, 4, 41, 78, 97 Progressive, 94, 97 Proline, 83, 89, 97 Prophylaxis, 4, 97 Prostaglandins, 13, 14, 29, 34, 45, 79, 86, 90, 97 Prostaglandins A, 90, 97 Prostate, 47, 97 Protein C, 40, 78, 97 Protein S, 80, 98 Proteins, 78, 79, 82, 83, 93, 95, 96, 98, 100 Proteinuria, 93, 98 Protons, 89, 98 Public Policy, 61, 98 Pyrexia, 38, 39, 98 Q Quiescent, 5, 98 R Race, 8, 38, 42, 43, 98 Racemic, 8, 38, 42, 43, 98 Radioactive, 88, 89, 91, 94, 98 Radioimmunoassay, 10, 98 Randomized, 6, 14, 86, 98 Ranitidine, 4, 98 Receptor, 5, 77, 79, 84, 98 Rectal, 22, 30, 98 Rectum, 79, 83, 87, 88, 91, 97, 98, 101 Recurrence, 41, 98 Red blood cells, 87, 89, 98 Reductase, 93, 98 Refer, 1, 81, 83, 98 Reflux, 43, 98 Regimen, 40, 86, 95, 98 Relapse, 41, 99 Remission, 98, 99 Renin, 6, 78, 99 Resection, 35, 99 Resorption, 40, 99 Respiration, 5, 82, 93, 99 Rheumatism, 34, 90, 99 Rheumatoid, 6, 8, 9, 10, 11, 13, 16, 17, 18, 20, 21, 22, 25, 28, 29, 30, 40, 87, 91, 94, 96, 99

Rheumatoid arthritis, 6, 8, 10, 11, 13, 16, 17, 18, 20, 21, 22, 25, 28, 29, 30, 40, 87, 91, 94, 96, 99 Risk factor, 3, 99 Risk patient, 4, 99 S Screening, 82, 99 Secondary tumor, 92, 99 Secretion, 89, 93, 94, 98, 99 Secretory, 94, 99 Sedative, 82, 99 Selenium, 10, 99 Semen, 97, 99 Senescence, 4, 99 Senile, 95, 99 Serum, 23, 24, 45, 78, 83, 98, 100 Serum Albumin, 23, 98, 100 Side effect, 53, 77, 90, 96, 100, 101, 102 Signs and Symptoms, 40, 99, 100 Skeletal, 93, 100 Skeleton, 87, 100 Small intestine, 86, 89, 90, 100, 103 Smooth muscle, 89, 93, 94, 100, 101 Sodium, 44, 45, 85, 88, 94, 100 Soft tissue, 81, 100 Solvent, 43, 82, 85, 94, 96, 100 Sorbitol, 92, 100 Specialist, 67, 85, 100 Species, 93, 98, 100, 102, 103 Sperm, 100, 101, 102 Spleen, 89, 91, 100 Splenomegaly, 100 Spondylitis, 87, 100 Stomach, 87, 88, 89, 94, 95, 98, 100 Stool, 83, 91, 101 Stress, 84, 94, 99, 101 Subcutaneous, 86, 101 Substance P, 92, 99, 101 Suction, 87, 101 Sulindac, 45, 101 Suppositories, 8, 28, 88, 101 Symphysis, 97, 101 Synovial, 21, 23, 24, 101 Synovial Fluid, 23, 24, 101 Synovial Membrane, 101 T Testicles, 101, 102 Therapeutics, 7, 9, 10, 11, 12, 14, 15, 17, 19, 22, 24, 25, 33, 34, 54, 101 Thoracic, 80, 101 Thoracotomy, 14, 101 Thorax, 91, 101

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Thrombin, 98, 101 Thrombocytopenia, 46, 101 Thrombomodulin, 98, 101 Thromboxanes, 79, 86, 101 Thyroxine, 78, 101 Tissue, 25, 40, 46, 78, 79, 80, 81, 84, 85, 86, 89, 90, 91, 92, 93, 96, 99, 100, 101 Tolmetin, 45, 101 Tomography, 81, 102 Tooth Preparation, 77, 102 Topical, 80, 85, 95, 102 Toxic, iv, 3, 5, 84, 99, 102 Toxicity, 4, 5, 86, 92, 102 Toxicology, 62, 102 Transdermal, 14, 102 Transfection, 80, 102 Translation, 78, 102 Trauma, 94, 102 Tryptophan, 83, 102 Tuberculosis, 91, 102 Tunica, 93, 102 U Ulcer, 4, 93, 102 Ulceration, 95, 102 Urethra, 97, 102 Uric, 40, 88, 89, 102

Urinary, 6, 13, 23, 81, 94, 102 Urine, 13, 23, 80, 91, 94, 98, 102 Uterus, 47, 82, 92, 95, 102 V Vagina, 82, 92, 102 Vasectomy, 6, 28, 102 Vasodilator, 81, 89, 102 Vein, 94, 102 Venous, 94, 98, 103 Venules, 81, 103 Veterinary Medicine, 61, 103 Villi, 103 Villous, 46, 103 Virulence, 102, 103 Vitro, 103 W White blood cell, 79, 82, 91, 92, 96, 103 Womb, 102, 103 X Xenograft, 78, 103 X-ray, 40, 81, 84, 94, 103 Y Yeasts, 96, 103 Z Zymogen, 97, 103

111

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Etodolac

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