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

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

Author: ICON Health Publications

8 downloads 324 Views 2MB Size Report

This content was uploaded by our users and we assume good faith they have the permission to share this book. If you own the copyright to this book and it is wrongfully on our website, we offer a simple DMCA procedure to remove your content from our site. Start by pressing the button below!

Report copyright / DMCA form

DOWNLOAD PDF

LEFLUNOMIDE 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

ii

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., 1960Leflunomide: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84481-X 1. Leflunomide-Popular works. I. Title.

iii

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.

iv

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 leflunomide. 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.

v

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.

vi

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

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON LEFLUNOMIDE .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Leflunomide................................................................................... 4 E-Journals: PubMed Central ......................................................................................................... 7 The National Library of Medicine: PubMed .................................................................................. 8 CHAPTER 2. NUTRITION AND LEFLUNOMIDE................................................................................. 35 Overview...................................................................................................................................... 35 Finding Nutrition Studies on Leflunomide ................................................................................. 35 Federal Resources on Nutrition ................................................................................................... 38 Additional Web Resources ........................................................................................................... 39 CHAPTER 3. CLINICAL TRIALS AND LEFLUNOMIDE ....................................................................... 41 Overview...................................................................................................................................... 41 Recent Trials on Leflunomide ...................................................................................................... 41 Keeping Current on Clinical Trials ............................................................................................. 42 CHAPTER 4. PATENTS ON LEFLUNOMIDE ....................................................................................... 45 Overview...................................................................................................................................... 45 Patents on Leflunomide................................................................................................................ 45 Patent Applications on Leflunomide............................................................................................ 50 Keeping Current .......................................................................................................................... 53 CHAPTER 5. BOOKS ON LEFLUNOMIDE........................................................................................... 55 Overview...................................................................................................................................... 55 Book Summaries: Federal Agencies.............................................................................................. 55 Book Summaries: Online Booksellers........................................................................................... 56 Chapters on Leflunomide ............................................................................................................. 56 CHAPTER 6. PERIODICALS AND NEWS ON LEFLUNOMIDE ............................................................. 59 Overview...................................................................................................................................... 59 News Services and Press Releases................................................................................................ 59 Academic Periodicals covering Leflunomide................................................................................ 62 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 63 Overview...................................................................................................................................... 63 U.S. Pharmacopeia....................................................................................................................... 63 Commercial Databases ................................................................................................................. 64 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 67 Overview...................................................................................................................................... 67 NIH Guidelines............................................................................................................................ 67 NIH Databases............................................................................................................................. 69 Other Commercial Databases....................................................................................................... 71 APPENDIX B. PATIENT RESOURCES ................................................................................................. 73 Overview...................................................................................................................................... 73 Patient Guideline Sources............................................................................................................ 73 Finding Associations.................................................................................................................... 75 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 77 Overview...................................................................................................................................... 77 Preparation................................................................................................................................... 77 Finding a Local Medical Library.................................................................................................. 77 Medical Libraries in the U.S. and Canada ................................................................................... 77 ONLINE GLOSSARIES.................................................................................................................. 83 Online Dictionary Directories ..................................................................................................... 83

viii Contents

LEFLUNOMIDE DICTIONARY................................................................................................... 85 INDEX .............................................................................................................................................. 121

1

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 leflunomide 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 leflunomide, 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 leflunomide, 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 leflunomide. 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 leflunomide, 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 leflunomide. The Editors

1

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

3

CHAPTER 1. STUDIES ON LEFLUNOMIDE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on leflunomide.

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

Leflunomide for RA: Defining Its Role Source: Journal of Musculoskeletal Medicine. 18(5): 277-282. May 2001. Summary: This journal article, the third in a series on new therapies for rheumatoid arthritis (RA), provides health professionals with information on the role of leflunomide in the management of RA. Leflunomide is a new disease modifying antirheumatic drug available to people who have RA. It works primarily through reversible inhibition of pyrimidine nucleotide synthesis. Following a loading dose of 100 milligrams for 3 days, 3 to 6 weeks are needed to achieve steady state blood levels of leflunomide. In the absence of such a loading dose, it takes approximately 2 months of treatment at a dosage of 20 milligrams per day to achieve this steady state. The clinical safety and efficacy of leflunomide have been assessed in three phase III clinical studies. Leflunomide was compared with methotrexate and placebo in one study, methotrexate

4

Leflunomide

alone in another study, and sulfasalazine and placebo in the third study. Results of these phase III trials indicate that leflunomide is equivalent to sulfasalazine and methotrexate in retarding radiographic progression of RA and is better than sulfasalazine in improving physical function. In one trial, leflunomide was better than methotrexate in improving physical function. Adverse events associated with leflunomide are similar to those of methotrexate and include diarrhea, rash, elevated liver function levels, and reversible alopecia. Leflunomide is not recommended for patients who are pregnant or trying to conceive. If significant adverse events occur, leflunomide can be quickly cleared from the system with cholestyramine washout. 2 figures, 2 tables, and 15 references. (AA-M).

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

Project Title: ANTIVIRAL LEFLUNOMIDE

ACTIVITY

OF

THE

IMMUNOSUPPRESSANT

Principal Investigator & Institution: Waldman, W J.; Pathology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2005 Summary: Post-transplantation pharmacologic immunosuppression puts transplant recipients at risk for development of opportunistic infections. Of these, cytomegalovirus (CMV) remains one of the most common sources of serious complications, frequently engaging the clinician in a struggle to balance graft-preserving immunosuppressive therapy with control of CMV disease. Our recent preliminary studies suggest that leflunomide, an experimental immunosuppressive agent currently in Phase I clinical trials in : transplant recipients, exhibits unique mechanisms of antiviral activity against CMV, including (traditional) drug-resistant isolates. This investigation is designed to assess the antiviral activity of leflunomide in vivo, and to resolve the molecular mechanisms underlying the antiviral activity of this agent. To determine the effectiveness of leflunomide in control of acute CMV disease, immunodeficient rats will be inoculated with CMV, treated with this agent (or otherimmunsuppressants or anti2

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

Studies

5

CMV drugs), and authorized at intervals. Salivary glands, spleen, and lungs will be examined histologically for viral pathology, and assayed for viral load by plaque assay. To determine the effectiveness of leflunomide in the prevention and reversal of viral reactivation, CMV latency will be established in immunocompetent rats and leflunomide (or other agents) will be administered prior to, or following radiationinduced viral reactivation. Animals will be authorized at intervals and assayed as above. Since leflunomide, a known inhibitor of protein kinase activity, appears to interfere with formation of the viral tegument (our preliminary observations), several major components of which are phosphoproteins, molecular mechanisms underlying the antiviral activity of leflunomide will be investigated first by assay of viral structural protein phosphorylation. CMV-infected human cells incubated in the presence or absence of leflunomide will be labeled with [32P] orthophosphate, lysed, and assayed by western blot (and confirmatory immunoprecipitation) using antibodies specific for tegument or other structural proteins. Phosphorylation patterns will be assayed by autoradiography and specific proteins will be identified and quantitated by immunoblot. Phosphoamino acids in precipitated phosphoproteins will be identified by two-dimensional electrophoresis and distribution of structural proteins will be assessed by immunogold electron microscopy. Since our preliminary data indicate that leflunomide attenuates activation of host cell transcription factors which contribute to viral gene activation, but does not inhibit viral gene transcription or DNA synthesis, we will also test the hypothesis that the antiviral activity of this agent is independent of its effect upon host cell transcription factors. Nuclear extracts derived from leflunomidetreated (or untreated) CMV-infected cells will be quantitatively analyzed by electrophoretic mobility shift assay for binding of CMV-relevant host transcription factors to their respective consensus DNA binding elements. Transfection with plasmid constructs containing reporter genes driven the CMV immediate early promoter/enhancer sequence will be employed to determine the impact of leflunomide upon CMV immediate early gene expression. Preliminary data predict that results of the proposed experiments will identify leflunomide as uniquely bifunctional in its ability to both preserve graft integrity and substantially reduce viral load. In addition, data generated by this investigation will provide the rationale for the development of leflunomide derivatives and related compounds possessing greater efficacy and/or with exclusively antiviral (but not imrnunosuppressive) activity, thereby broadening the target population to include AIDS patients and other individuals susceptible to opportunistic infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF T KINASE DISREGULATED TUMORS BY LEF AND MABS Principal Investigator & Institution: Xu, Xiulong; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 26-JAN-1998; Project End 31-DEC-2002 Summary: (Applicant's Abstract) Most approaches to cancer therapy have centered around the idea that cytotoxic drugs can be used to eradicate proliferating neoplastic cells. Cytotoxicity is generally thought to evolve from the presence of drug-induced damage to genetic material, and DNA has served admirably as a primary focus for drug development. However, improved understanding of receptor-mediated signal transduction and growth control pathways in the last decade has reshaped the strategy for drug development: the inhibitors and monoclonal antibodies that disrupt signal transduction pathways now provide a useful basis for the rational design of new cancer

6

Leflunomide

therapies and may represent a new class of chemotherapeutic agents. Leflunomide, a novel immunomodulatory drug, has two biochemical activities: inhibition of tyrosine phosphorylation and pyrimidine nucleotide synthesis. The applicant's recent studies of the lymphoproliferative and autoimmune disease in MRL-lpr/lpr mice have demonstrated that inhibition of protein tyrosine phosphorylation but not interference with pyrimidine nucleotide synthesis by leflunomide represents its in vivo mode of action. This observation opens the possibility that leflunomide might be exploited as a novel antitumor agent to be used for controlling tyrosine kinase dysregulated-tumors. The applicant's preliminary results show that leflunomide is very effective in the control of platelet-derived growth factor-overexpressed C6 glioma implanted in athymic mice. Here he proposes to extend these observations by examining the mechanisms of leflunomide-mediated antitumor activities in several types of tyrosine kinasedysregulated tumor cell lines in vitro and in vivo. He will also test whether combination therapy of leflunomide with anti-growth factor receptor mAbs will achieve synergistic therapeutic effects. Finally, he will test whether leflunomide can inhibit the kinase activity of vascular endothelial growth factor receptor and control angiogenesis, and to test whether the antitumor activity of leflunomide is mediated by control of angiogenesis in solid tumors. Demonstration that leflunomide can inhibit the proliferation of tumor cells through inhibition of tyrosine kinase activity, rather than cytotoxic mechanisms, would suggest its use as a novel class of differentiation agent for the treatment of tyrosine kinase-driven tumors. In addition, the identification of an agent that has both immunosuppressive as well as anti-tumor potential could be of clinical significance to transplant patients who, under currently available immunosuppression, become susceptible to lymphoproliferative disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEFLUNOMIDE VS PLACEBO FOR ACTIVE RHEUMATOID ARTHRITIS Principal Investigator & Institution: Weisman, Michael H.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: LFM-A13: AN ANTILEUKEMIC/ANTITHROMBOTIC AGENT Principal Investigator & Institution: Mahajan, Sandeep; Paradigm Pharmaceuticals, Llc 2685 Patton Rd St. Paul, Mn 55113 Timing: Fiscal Year 2004; Project Start 15-AUG-2002; Project End 31-DEC-2005 Summary: (provided by applicant): We have rationally designed the leflunomide metabolite analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13) as a specific inhibitor of the protein tyrosine kinase, Bruton's tyrosine kinase (BTK). LFM-A13 is a chemosensitizing anti-leukemic agent with antithrombotic properties. Our preclinical studies established that LFM-A13 has a favorable safety and pharmacokinetics profile. LFM-A13 has been formulated for oral administration (LFM-A13-F). Under SPECIFIC AIM 1, we will study the toxicity profile of LFM-A13-F in rats and dogs and 2) synthesize and formulate large quantities of LFMA13 under GMP conditions to be used for human clinical trials. Based on the toxicity studies done in mice, we hypothesize that LFM-A13-F will not cause acute, subacute, or chronic toxicity at the proposed dose levels. Under SPECIFIC AIM 2, large scale

Studies

7

synthesis and evaluation of LFM-A13-F as hard gelatin capsules will be carried under Good Manufacturing Practice (GMP) to comply with FDA regulations and to ensure preparation of clinical grade LFM-A13-F for human clinical trials. We will use synthetic procedures developed during the phase I studies. In order to achieve specific aim 2 we have already identified FDA approved facilities for the synthesis and formulation of LFM-A13. The results obtained in specific aim #1 and specific aim #2 will provide the critical information for further testing of this agent in human subjects under Phase III. This research will facilitate the bench-to-bedside development of LFM-A13 as the protype of a new class of anti-leukemic agents with anti-thrombotic properties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF IMMUNOPHILINS AND RELATED PROTEINS Principal Investigator & Institution: Clardy, Jon C.; Professor; Chemistry and Chemical Biology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 10-JUL-1992; Project End 31-DEC-2002 Summary: Immunophilins and related proteins participate in many fundamental biological processes, and this project's overall goal is analyzing these processes in structural terms. In addition to providing a basic structural understanding of these important proteins, the project has practical implications for prevent graft versus. host disease in transplant patients, alleviating autoimmune diseases such as rheumatoid arthritis and insulin- dependent diabetes, and developing small molecules for regulated gene therapy. Separate projects include: Structures of the large immunophilins FKBP51 and FKB952 along with their partners in the steroid receptor complex Hip and Hop. Structure of FRAP, a member of the ATM family of proteins involved in cell cycle checkpoints and DNA repair. Structure of dihydroorotate dehydrogenase, the protein target of the rheumatoid arthritis drug leflunomide (Arava) and the anti- cancer agent brequinar. Structure of the dimerizing agents based on FKBP12-rapamycin- FRB that are clinically useful in small molecule regulated gene therapy. Structures such as fyn SH2pYEEI/FK506-FKBP52 that illustrate the concept of using borrowed endogenous proteins to moderate the binding of hybrid small molecules. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “leflunomide” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for leflunomide in the PubMed Central database: 3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

8

•

Leflunomide

Leflunomide can potentiate the anticoagulant effect of warfarin. by Lim V, Pande I.; 2002 Dec 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137810

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with leflunomide, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “leflunomide” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for leflunomide (hyperlinks lead to article summaries): •

A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Author(s): Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gomor B, Van Den Bosch F, Nordstrom D, Bjorneboe O, Dahl R, Horslev-Petersen K, Rodriguez De La Serna A, Molloy M, Tikly M, Oed C, Rosenburg R, Loew-Friedrich I. Source: Rheumatology (Oxford, England). 2000 June; 39(6): 655-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10888712

•

A novel mechanism of action of the immunomodulatory drug, leflunomide: augmentation of the immunosuppressive cytokine, TGF-beta 1, and suppression of the immunostimulatory cytokine, IL-2. Author(s): Cao WW, Kao PN, Aoki Y, Xu JC, Shorthouse RA, Morris RE. Source: Transplantation Proceedings. 1996 December; 28(6): 3079-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8962191

•

A771726, the active metabolite of leflunomide, directly inhibits the activity of cyclooxygenase-2 in vitro and in vivo in a substrate-sensitive manner. Author(s): Hamilton LC, Vojnovic I, Warner TD. Source: British Journal of Pharmacology. 1999 August; 127(7): 1589-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10455314

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

Studies

9

•

Active leflunomide metabolite inhibits interleukin 1beta, tumour necrosis factor alpha, nitric oxide, and metalloproteinase-3 production in activated human synovial tissue cultures. Author(s): Elkayam O, Yaron I, Shirazi I, Judovitch R, Caspi D, Yaron M. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 440-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695157

•

Alopecia areata in a patient with rheumatoid arthritis treated with leflunomide. Author(s): Gottenberg JE, Venancie PY, Mariette X. Source: The Journal of Rheumatology. 2002 August; 29(8): 1806-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180755

•

Aminotransferase levels during treatment of rheumatoid arthritis with leflunomide in clinical practice. Author(s): Hoi A, Littlejohn GO. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 379. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634251

•

Anti-glomerular basement membrane antibody-associated renal failure in a patient with leflunomide-treated rheumatoid arthritis. Author(s): Bruyn GA, Veenstra RP, Halma C, Grond J. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1164-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687568

•

Anti-HIV-1 activity of leflunomide: a comparison with mycophenolic acid and hydroxyurea. Author(s): Schlapfer E, Fischer M, Ott P, Speck RF. Source: Aids (London, England). 2003 July 25; 17(11): 1613-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853743

•

Anti-inflammatory effects of leflunomide on cultured synovial macrophages from patients with rheumatoid arthritis. Author(s): Cutolo M, Sulli A, Ghiorzo P, Pizzorni C, Craviotto C, Villaggio B. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634225

•

Beneficial effects of leflunomide in glucocorticoid- and methotrexate-resistant Takayasu's arteritis. Author(s): Haberhauer G, Kittl EM, Dunky A, Feyertag J, Bauer K. Source: Clin Exp Rheumatol. 2001 July-August; 19(4): 477-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11491512

10

Leflunomide

•

Benefits of leflunomide in systemic lupus erythematosus: a pilot observational study. Author(s): Remer CF, Weisman MH, Wallace DJ. Source: Lupus. 2001; 10(7): 480-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11480845

•

Bullous pemphigoid treated with leflunomide: a novel immunomodulatory agent. Author(s): Nousari HC, Anhalt GJ. Source: Archives of Dermatology. 2000 October; 136(10): 1204-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11030765

•

Cell cycle regulation and inhibition of de novo pyrimidine biosynthesis by leflunomide. Author(s): Schorlemmer HU, Milbert U, Zeitter D, Haun G, Wunschel M, Bartlett RR. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1999 December; 48 Suppl 2: S115-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667841

•

Clinical experience with leflunomide in rheumatoid arthritis. Leflunomide Investigators' Group. Author(s): Rozman B. Source: J Rheumatol Suppl. 1998 July; 53: 27-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9666415

•

Clinical improvement as reflected in measures of function and health-related quality of life following treatment with leflunomide compared with methotrexate in patients with rheumatoid arthritis: sensitivity and relative efficiency to detect a treatment effect in a twelve-month, placebo-controlled trial. Leflunomide Rheumatoid Arthritis Investigators Group. Author(s): Tugwell P, Wells G, Strand V, Maetzel A, Bombardier C, Crawford B, Dorrier C, Thompson A. Source: Arthritis and Rheumatism. 2000 March; 43(3): 506-14. Erratum In: Arthritis Rheum 2000 June; 43(6): 1345. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728742

•

Clinical pharmacokinetics of leflunomide. Author(s): Rozman B. Source: Clinical Pharmacokinetics. 2002; 41(6): 421-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074690

Studies

11

•

Comparative assessment of leflunomide and methotrexate for the treatment of rheumatoid arthritis, by dynamic enhanced magnetic resonance imaging. Author(s): Reece RJ, Kraan MC, Radjenovic A, Veale DJ, O'Connor PJ, Ridgway JP, Gibbon WW, Breedveld FC, Tak PP, Emery P. Source: Arthritis and Rheumatism. 2002 February; 46(2): 366-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11840438

•

Comparative effects of malononitriloamide analogs of leflunomide on whole blood lymphocyte stimulation in humans, rhesus macaques, cats, dogs, and rats. Author(s): Gregory CR, Silva HT, Patz JD, Morris RE. Source: Transplantation Proceedings. 1998 June; 30(4): 1047-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636423

•

Comparative study of the clinical efficacy of four DMARDs (leflunomide, methotrexate, cyclosporine, and levamisole) in patients with rheumatoid arthritis. Author(s): Popovic M, Stefanovic D, Pejnovic N, Popovic R, Glisic B, Obradovic S, Dimitrijevic M. Source: Transplantation Proceedings. 1998 December; 30(8): 4135-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9865325

•

Comparison of rheumatoid arthritis care costs in patients starting therapy with leflunomide versus etanercept. Author(s): Yazdani C, McLaughlin T, Cummins G, Doyle J. Source: Am J Manag Care. 2001 September; 7(13 Suppl): S419-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11594238

•

Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Author(s): Kremer JM, Genovese MC, Cannon GW, Caldwell JR, Cush JJ, Furst DE, Luggen ME, Keystone E, Weisman MH, Bensen WM, Kaine JL, Ruderman EM, Coleman P, Curtis DL, Kopp EJ, Kantor SM, Waltuck J, Lindsley HB, Markenson JA, Strand V, Crawford B, Fernando I, Simpson K, Bathon JM. Source: Annals of Internal Medicine. 2002 November 5; 137(9): 726-33. Summary for Patients In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416946

•

Cost effectiveness of adding leflunomide to a 5-year strategy of conventional diseasemodifying antirheumatic drugs in patients with rheumatoid arthritis. Author(s): Maetzel A, Strand V, Tugwell P, Wells G, Bombardier C. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 655-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522841

12

Leflunomide

•

Differential modulation of pro- and anti-inflammatory cytokine receptors by N-(4trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acid amide (A77 1726), the physiologically active metabolite of the novel immunomodulator leflunomide. Author(s): Mirmohammadsadegh A, Homey B, Abts HF, Kohrer K, Ruzicka T, Michel G. Source: Biochemical Pharmacology. 1998 May 1; 55(9): 1523-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10076546

•

Dihydroorotate dehydrogenase is a target for the biological effects of leflunomide. Author(s): Williamson RA, Yea CM, Robson PA, Curnock AP, Gadher S, Hambleton AB, Woodward K, Bruneau JM, Hambleton P, Spinella-Jaegle S, Morand P, Courtin O, Sautes C, Westwood R, Hercend T, Kuo EA, Ruuth E. Source: Transplantation Proceedings. 1996 December; 28(6): 3088-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8962196

•

Disease modification in rheumatoid arthritis with leflunomide. Author(s): Emery P. Source: Scand J Rheumatol Suppl. 1999; 112: 9-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668522

•

Economic comparison of leflunomide and methotrexate in patients with rheumatoid arthritis: an evaluation based on a 1-year randomised controlled trial. Author(s): Maetzel A, Strand V, Tugwell P, Wells G, Bombardier C. Source: Pharmacoeconomics. 2002; 20(1): 61-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817993

•

Effect of hemodialysis on leflunomide plasma concentrations. Author(s): Beaman JM, Hackett LP, Luxton G, Illett KF. Source: The Annals of Pharmacotherapy. 2002 January; 36(1): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816264

•

Effect of leflunomide on constitutive and inducible pathways of cellular eicosanoid generation. Author(s): Weithmann KU, Jeske S, Schlotte V. Source: Agents Actions. 1994 May; 41(3-4): 164-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7942324

•

Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers. Author(s): Zielinski T, Muller HJ, Bartlett RR. Source: Agents Actions. 1993; 38 Spec No: C80-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8317329

Studies

13

•

Effects of leflunomide and other immunosuppressive agents on T cell proliferation in vitro. Author(s): Chong AS, Rezai K, Gebel HM, Finnegan A, Foster P, Xu X, Williams JW. Source: Transplantation. 1996 January 15; 61(1): 140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8560553

•

Effects of leflunomide on immune responses and models of inflammation. Author(s): Bartlett RR, Anagnostopulos H, Zielinski T, Mattar T, Schleyerbach R. Source: Springer Seminars in Immunopathology. 1993; 14(4): 381-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8322168

•

Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group. Author(s): Smolen JS, Kalden JR, Scott DL, Rozman B, Kvien TK, Larsen A, LoewFriedrich I, Oed C, Rosenburg R. Source: Lancet. 1999 January 23; 353(9149): 259-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929017

•

Efficacy and safety of leflunomide in active rheumatoid arthritis. Author(s): Smolen JS, Emery P. Source: Rheumatology (Oxford, England). 2000 June; 39 Suppl 1: 48-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11001380

•

Efficacy and safety of the new DMARD leflunomide: comparison to placebo and sulfasalazine in active rheumatoid arthritis. Author(s): Smolen JS. Source: Scand J Rheumatol Suppl. 1999; 112: 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668523

•

Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden. Author(s): Geborek P, Crnkic M, Petersson IF, Saxne T; South Swedish Arthritis Treatment Group. Source: Annals of the Rheumatic Diseases. 2002 September; 61(9): 793-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176803

•

Exfoliative dermatitis induced by leflunomide therapy. Author(s): Bandyopadhyay D. Source: The Journal of Dermatology. 2003 November; 30(11): 845-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684946

14

Leflunomide

•

Experiences with leflunomide in solid organ transplantation. Author(s): Williams JW, Mital D, Chong A, Kottayil A, Millis M, Longstreth J, Huang W, Brady L, Jensik S. Source: Transplantation. 2002 February 15; 73(3): 358-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11884931

•

Exposure of T lymphocytes to leflunomide but not to dexamethasone favors the production by monocytic cells of interleukin-1 receptor antagonist and the tissueinhibitor of metalloproteinases-1 over that of interleukin-1beta and metalloproteinases. Author(s): Deage V, Burger D, Dayer JM. Source: European Cytokine Network. 1998 December; 9(4): 663-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9889411

•

Fatal hepatitis with leflunomide and itraconazole. Author(s): Legras A, Bergemer-Fouquet AM, Jonville-Bera AP. Source: The American Journal of Medicine. 2002 September; 113(4): 352-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12361833

•

Function and health-related quality of life: results from a randomized controlled trial of leflunomide versus methotrexate or placebo in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group. Author(s): Strand V, Tugwell P, Bombardier C, Maetzel A, Crawford B, Dorrier C, Thompson A, Wells G. Source: Arthritis and Rheumatism. 1999 September; 42(9): 1870-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10513801

•

Immunosuppressants leflunomide and mycophenolic acid inhibit fibroblast IL-6 production by distinct mechanisms. Author(s): Miljkovic Dj, Samardzic T, Drakulic D, Stosic-Grujicic S, Trajkovic V. Source: Cytokine. 2002 August 21; 19(4): 181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297111

•

Immunosuppressive effects of leflunomide in experimental chronic vascular rejection. Author(s): Swan SK, Crary GS, Guijarro C, O'Donnell MP, Keane WF, Kasiske BL. Source: Transplantation. 1995 October 27; 60(8): 887-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7482756

Studies

15

•

Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. Author(s): Manna SK, Aggarwal BB. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 February 15; 162(4): 2095102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9973483

•

Impact of leflunomide versus biologic agents on the costs of care for rheumatoid arthritis in a managed care population. Author(s): Ollendorf DA, Peterson AN, Doyle J, Huse DM. Source: Am J Manag Care. 2002 May; 8(7 Suppl): S203-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022236

•

Improved functional ability in patients with rheumatoid arthritis--longterm treatment with leflunomide versus sulfasalazine. European Leflunomide Study Group. Author(s): Kalden JR, Scott DL, Smolen JS, Schattenkirchner M, Rozman B, Williams BD, Kvien TK, Jones P, Williams RB, Oed C, Rosenburg R; European Leflunomide Study Group. Source: The Journal of Rheumatology. 2001 September; 28(9): 1983-91. Erratum In: J Rheumatol 2002 January; 29(1): 205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11550964

•

In vivo activity of leflunomide: pharmacokinetic analyses and mechanism of immunosuppression. Author(s): Chong AS, Huang W, Liu W, Luo J, Shen J, Xu W, Ma L, Blinder L, Xiao F, Xu X, Clardy C, Foster P, Williams JA. Source: Transplantation. 1999 July 15; 68(1): 100-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10428276

•

Infliximab and leflunomide combination therapy in rheumatoid arthritis: an openlabel study. Author(s): Kiely PD, Johnson DM. Source: Rheumatology (Oxford, England). 2002 June; 41(6): 631-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048288

•

Inhibition of angiogenesis-related endothelial activity by the experimental immunosuppressive agent leflunomide. Author(s): Waldman WJ, Bickerstaff A, Gordillo G, Orosz K, Knight DA, Orosz CG. Source: Transplantation. 2001 November 15; 72(9): 1578-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707749

16

Leflunomide

•

Inhibition of cytomegalovirus in vitro and in vivo by the experimental immunosuppressive agent leflunomide. Author(s): Waldman WJ, Knight DA, Blinder L, Shen J, Lurain NS, Miller DM, Sedmak DD, Williams JW, Chong AS. Source: Intervirology. 1999; 42(5-6): 412-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702725

•

Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Author(s): Greene S, Watanabe K, Braatz-Trulson J, Lou L. Source: Biochemical Pharmacology. 1995 September 7; 50(6): 861-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7575649

•

Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide. Author(s): Knight DA, Hejmanowski AQ, Dierksheide JE, Williams JW, Chong AS, Waldman WJ. Source: Transplantation. 2001 January 15; 71(1): 170-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11211189

•

Inhibition of HIV replication by A77 1726, the active metabolite of leflunomide, in combination with pyrimidine nucleoside reverse transcriptase inhibitors. Author(s): Hossain MM, Margolis DM. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2001 October 1; 28(2): 199-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588518

•

Inhibition of neutrophil migration soon after initiation of treatment with leflunomide or methotrexate in patients with rheumatoid arthritis: findings in a prospective, randomized, double-blind clinical trial in fifteen patients. Author(s): Kraan MC, de Koster BM, Elferink JG, Post WJ, Breedveld FC, Tak PP. Source: Arthritis and Rheumatism. 2000 July; 43(7): 1488-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10902750

•

Inhibition of protein tyrosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide. Author(s): Xu X, Williams JW, Bremer EG, Finnegan A, Chong AS. Source: The Journal of Biological Chemistry. 1995 May 26; 270(21): 12398-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7759480

Studies

17

•

Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide. Author(s): Mattar T, Kochhar K, Bartlett R, Bremer EG, Finnegan A. Source: Febs Letters. 1993 November 15; 334(2): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8224241

•

Innovative treatment approaches for rheumatoid arthritis. Cyclosporin, leflunomide and nitrogen mustard. Author(s): Furst DE. Source: Baillieres Clin Rheumatol. 1995 November; 9(4): 711-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8591650

•

Is leflunomide as safe and effective in the treatment of rheumatoid arthritis as other DMARDs? Author(s): Schooff M, Wickersham J. Source: American Family Physician. 2003 September 1; 68(5): 849-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678131

•

Is the recommended dose of leflunomide the best regimen to treat rheumatoid arthritis patients? Author(s): Erra A, Tomas C, Barcelo P, Vilardell M, Marsal S. Source: Rheumatology (Oxford, England). 2003 September; 42(9): 1123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923276

•

Is there a place for leflunomide in the treatment of rheumatoid arthritis? Author(s): Breedveld FC. Source: Lancet. 2001 October 13; 358(9289): 1198-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11675052

•

Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions leading to transplantation rejection. Author(s): Bartlett RR, Dimitrijevic M, Mattar T, Zielinski T, Germann T, Rude E, Thoenes GH, Kuchle CC, Schorlemmer HU, Bremer E, et al. Source: Agents Actions. 1991 January; 32(1-2): 10-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2058454

•

Leflunomide and anti-glomerular basement membrane glomerulonephritis: comment on the letter by Bruyn et al. Author(s): Chow KM, Szeto CC. Source: Arthritis and Rheumatism. 2004 January; 50(1): 336; Author Reply 336-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730637

18

Leflunomide

•

Leflunomide and hypertension. Author(s): Rozman B, Praprotnik S, Logar D, Tomsic M, Hojnik M, Kos-Golja M, Accetto R, Dolenc P. Source: Annals of the Rheumatic Diseases. 2002 June; 61(6): 567-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006342

•

Leflunomide and malononitrilamides. Author(s): Silva Junior HT, Morris RE. Source: The American Journal of the Medical Sciences. 1997 May; 313(5): 289-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9145039

•

Leflunomide and methotrexate. Author(s): Laan RF, van Riel PL, van de Putte LB. Source: Current Opinion in Rheumatology. 2001 May; 13(3): 159-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11333342

•

Leflunomide and rheumatoid arthritis: a systematic review of effectiveness, safety and cost implications. Author(s): Hewitson PJ, Debroe S, McBride A, Milne R. Source: Journal of Clinical Pharmacy and Therapeutics. 2000 August; 25(4): 295-302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971781

•

Leflunomide Aventis Pharma. Author(s): Kaplan MJ. Source: Curr Opin Investig Drugs. 2001 February; 2(2): 222-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11816835

•

Leflunomide can potentiate the anticoagulant effect of warfarin. Author(s): Lim V, Pande I. Source: Bmj (Clinical Research Ed.). 2002 December 7; 325(7376): 1333. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12468482

•

Leflunomide decreases joint erosions and induces reparative changes in a patient with psoriatic arthritis. Author(s): Cuchacovich M, Soto L. Source: Annals of the Rheumatic Diseases. 2002 October; 61(10): 942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12228172

Studies

19

•

Leflunomide for active rheumatoid arthritis. Author(s): Ferraccioli GF, De Vita S. Source: Lancet. 1999 May 29; 353(9167): 1883; Author Reply 1883-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10359440

•

Leflunomide for active rheumatoid arthritis. Author(s): Bruyn GA, Griep EN, Korff KJ. Source: Lancet. 1999 May 29; 353(9167): 1883; Author Reply 1883-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10359439

•

Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Author(s): Sanders S, Harisdangkul V. Source: The American Journal of the Medical Sciences. 2002 April; 323(4): 190-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12003373

•

Leflunomide for the treatment of rheumatoid arthritis. Author(s): Miceli-Richard C, Dougados M. Source: Expert Opinion on Pharmacotherapy. 2003 June; 4(6): 987-97. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783594

•

Leflunomide for the treatment of rheumatoid arthritis. Author(s): Olsen NJ, Strand V, Kremer JM. Source: Bulletin on the Rheumatic Diseases. 1999; 48(8): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628065

•

Leflunomide for the treatment of rheumatoid arthritis: a systematic review and metaanalysis. Author(s): Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. Source: The Journal of Rheumatology. 2003 June; 30(6): 1182-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784387

•

Leflunomide for the treatment of systemic lupus erythematosus: comment on the article by McMurray. Author(s): Barthel HR. Source: Arthritis and Rheumatism. 2001 October; 45(5): 472. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11642648

20

Leflunomide

•

Leflunomide for treating rheumatoid arthritis. Author(s): Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. Source: Cochrane Database Syst Rev. 2003; (1): Cd002047. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535423

•

Leflunomide improves quality of life in rheumatoid arthritis. Author(s): Scott DL. Source: Scand J Rheumatol Suppl. 1999; 112: 23-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668524

•

Leflunomide in Crohn's disease--the open-label case series and the Texas sharpshooter. Author(s): Sachar DB. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 99-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869876

•

Leflunomide in treatment of rheumatoid arthritis. Author(s): McCarey DW, Capell HA, Madhok R. Source: Lancet. 2002 March 30; 359(9312): 1158. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11943298

•

Leflunomide induced fevers, thrombocytosis, and leukocytosis in a patient with relapsing polychondritis. Author(s): Koenig AS, Abruzzo JL. Source: The Journal of Rheumatology. 2002 January; 29(1): 192-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824960

•

Leflunomide induced vasculitis--a dose-response relationship. Author(s): Chan AT, Bradlow A, McNally J. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 492-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12626811

•

Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated Tlymphocytes from healthy humans. Author(s): Ruckemann K, Fairbanks LD, Carrey EA, Hawrylowicz CM, Richards DF, Kirschbaum B, Simmonds HA. Source: The Journal of Biological Chemistry. 1998 August 21; 273(34): 21682-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9705303

Studies

21

•

Leflunomide interferes with pyrimidine nucleotide biosynthesis. Author(s): Cherwinski HM, Byars N, Ballaron SJ, Nakano GM, Young JM, Ransom JT. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1995 August; 44(8): 317-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8581517

•

Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappa B, activator protein-1, c-Jun N-terminal protein kinase, and apoptosis. Author(s): Manna SK, Mukhopadhyay A, Aggarwal BB. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 November 15; 165(10): 5962-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11067959

•

Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator therapy. Author(s): Prajapati DN, Knox JF, Emmons J, Saeian K, Csuka ME, Binion DG. Source: Journal of Clinical Gastroenterology. 2003 August; 37(2): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869881

•

Leflunomide use during the first 33 months after food and drug administration approval: experience with a national cohort of 3,325 patients. Author(s): Siva C, Eisen SA, Shepherd R, Cunningham F, Fang MA, Finch W, Salisbury D, Singh JA, Stern R, Zarabadi SA. Source: Arthritis and Rheumatism. 2003 December 15; 49(6): 745-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673959

•

Leflunomide versus methotrexate: a comparison of the European and American experience. Author(s): Schiff MH. Source: Scand J Rheumatol Suppl. 1999; 112: 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668525

•

Leflunomide, a new disease-modifying anti-rheumatic drug and the never ending rheumatoid arthritis story. Author(s): Smolen JS, Graninger WB, Emery P. Source: Rheumatology (Oxford, England). 2000 July; 39(7): 689-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10908683

22

Leflunomide

•

Leflunomide, a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase II clinical trial. Author(s): Bao C, Chen S, Gu Y, Lao Z, Ni L, Yu Q, Xu J, Li X, Liu J, Sun L, He P, Ma J, Xu S, Ding C. Source: Chinese Medical Journal. 2003 August; 116(8): 1228-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935395

•

Leflunomide, a novel immunomodulating drug, inhibits homotypic adhesion of mononuclear cells in rheumatoid arthritis. Author(s): Dimitrijevic M, Bartlett RR. Source: Transplantation Proceedings. 1996 December; 28(6): 3086-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8962195

•

Leflunomide, a novel immunomodulating drug, inhibits homotypic adhesion of peripheral blood and synovial fluid mononuclear cells in rheumatoid arthritis. Author(s): Dimitrijevic M, Bartlett RR. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1996 November; 45(11): 550-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8951506

•

Leflunomide, a novel immunomodulator for the treatment of active rheumatoid arthritis. Author(s): Goldenberg MM. Source: Clinical Therapeutics. 1999 November; 21(11): 1837-52; Discussion 1821. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10890256

•

Leflunomide, a novel immunomodulatory agent: in vitro analyses of the mechanism of immunosuppression. Author(s): Chong AS, Gebel H, Finnegan A, Petraitis EE, Jiang XL, Sankary HN, Foster P, Williams JW. Source: Transplantation Proceedings. 1993 February; 25(1 Pt 1): 747-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8438466

•

Leflunomide, a novel immunosuppressive agent. The mechanism of inhibition of T cell proliferation. Author(s): Chong AS, Finnegan A, Jiang X, Gebel H, Sankary HN, Foster P, Williams JW. Source: Transplantation. 1993 June; 55(6): 1361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8390735

Studies

23

•

Leflunomide, a reversible inhibitor of pyrimidine biosynthesis? Author(s): Zielinski T, Zeitter D, Muller S, Bartlett RR. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1995 August; 44 Suppl 2: S207-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8548402

•

Leflunomide, an immunorestoring drug for the therapy of autoimmune disorders, especially rheumatoid arthritis. Author(s): Bartlett RR, Brendel S, Zielinski T, Schorlemmer HU. Source: Transplantation Proceedings. 1996 December; 28(6): 3074-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8962190

•

Leflunomide, mycophenolic acid and matrix metalloproteinase inhibitors. Author(s): Furst DE. Source: Rheumatology (Oxford, England). 1999 November; 38 Suppl 2: 14-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10646484

•

Leflunomide. Author(s): Cohen SB, Iqbal I. Source: Int J Clin Pract. 2003 March; 57(2): 115-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661795

•

Leflunomide: a new DMARD for rheumatoid arthritis. Author(s): Emery P. Source: Hosp Med. 2000 May; 61(5): 344-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953742

•

Leflunomide: a novel DMARD for the treatment of rheumatoid arthritis. Author(s): Alldred A, Emery P. Source: Expert Opinion on Pharmacotherapy. 2001 January; 2(1): 125-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336574

•

Leflunomide: a review of its use in active rheumatoid arthritis. Author(s): Prakash A, Jarvis B. Source: Drugs. 1999 December; 58(6): 1137-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10651393

24

Leflunomide

•

Leflunomide: an active antiinflammatory and antiproliferative agent in models of dermatologic disease. Author(s): Kurtz ES, Bailey SC, Arshad F, Lee AA, Przekop PA. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 1995 August; 44 Suppl 2: S187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8548390

•

Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Author(s): Herrmann ML, Schleyerbach R, Kirschbaum BJ. Source: Immunopharmacology. 2000 May; 47(2-3): 273-89. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10878294

•

Leflunomide: mode of action in the treatment of rheumatoid arthritis. Author(s): Breedveld FC, Dayer JM. Source: Annals of the Rheumatic Diseases. 2000 November; 59(11): 841-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11053058

•

Leflunomide: new antirheumatic drug. Effect on pregnancy outcomes. Author(s): Kozer E, Moretti ME, Koren G. Source: Can Fam Physician. 2001 April; 47: 721-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11340750

•

Leflunomide-associated skin ulceration. Author(s): McCoy CM. Source: The Annals of Pharmacotherapy. 2002 June; 36(6): 1009-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022903

•

Leflunomide-associated weight loss in rheumatoid arthritis. Author(s): Coblyn JS, Shadick N, Helfgott S. Source: Arthritis and Rheumatism. 2001 May; 44(5): 1048-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352235

•

Leishmaniasis in Israel: reservoir hosts, sandfly vectors and leishmanial strains in the Negev, Central Arava and along the Dead Sea. Author(s): Schlein Y, Warburg A, Schnur LF, Le Blancq SM, Gunders AE. Source: Transactions of the Royal Society of Tropical Medicine and Hygiene. 1984; 78(4): 480-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6385358

Studies

25

•

Life-threatening reversible bone marrow toxicity in a rheumatoid arthritis patient switched from leflunomide to infliximab. Author(s): Marchesoni A, Arreghini M, Panni B, Battafarano N, Uziel L. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 193-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509641

•

Measurement of the active leflunomide metabolite (A77 1726) by reverse-phase highperformance liquid chromatography. Author(s): Dias VC, Lucien J, LeGatt DF, Yatscoff RW. Source: Therapeutic Drug Monitoring. 1995 February; 17(1): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7725383

•

Mechanism of action for leflunomide in rheumatoid arthritis. Author(s): Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Strand V, Kirschbaum BJ. Source: Clinical Immunology (Orlando, Fla.). 1999 December; 93(3): 198-208. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10600330

•

Mechanism of action of leflunomide in rheumatoid arthritis. Author(s): Fox RI. Source: J Rheumatol Suppl. 1998 July; 53: 20-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9666414

•

Mechanism of the antiproliferative action of leflunomide. A77 1726, the active metabolite of leflunomide, does not block T-cell receptor-mediated signal transduction but its antiproliferative effects are antagonized by pyrimidine nucleosides. Author(s): Cao WW, Kao PN, Chao AC, Gardner P, Ng J, Morris RE. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1995 November-December; 14(6 Pt 1): 1016-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8719445

•

Methotrexate and leflunomide combination therapy for patients with active rheumatoid arthritis. Author(s): Mroczkowski PJ, Weinblatt ME, Kremer JM. Source: Clin Exp Rheumatol. 1999 November-December; 17(6 Suppl 18): S66-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10589360

26

Leflunomide

•

Methotrexate and leflunomide: biochemical basis for combination therapy in the treatment of rheumatoid arthritis. Author(s): Kremer JM. Source: Seminars in Arthritis and Rheumatism. 1999 August; 29(1): 14-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468411

•

Modulation of human peripheral blood mononuclear cell activation by the combination of leflunomide and pentoxifylline. Author(s): Stojic Vukanic Z, Dimitrijevic M, Colic M, Popovic P, Jandric D. Source: Transplantation Proceedings. 2001 May; 33(3): 2137-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377478

•

Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunomide and methotrexate in patients with active rheumatoid arthritis. Findings in a prospective, randomized, double-blind, parallel-design clinical trial in thirtynine patients at two centers. Author(s): Kraan MC, Reece RJ, Barg EC, Smeets TJ, Farnell J, Rosenburg R, Veale DJ, Breedveld FC, Emery P, Tak PP. Source: Arthritis and Rheumatism. 2000 August; 43(8): 1820-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10943872

•

Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Author(s): Brazelton TR, Morris RE. Source: Current Opinion in Immunology. 1996 October; 8(5): 710-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8902398

•

Monitoring leflunomide (Arava) as a new potential teratogen. Author(s): Lyons Jones K, Johnson DL, Chambers CD. Source: Teratology. 2002 May; 65(5): 200-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967915

•

Multiple inhibitor analysis of the brequinar and leflunomide binding sites on human dihydroorotate dehydrogenase. Author(s): McLean JE, Neidhardt EA, Grossman TH, Hedstrom L. Source: Biochemistry. 2001 February 20; 40(7): 2194-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11329288

•

Mycophenolate mofetil and leflunomide: promising compounds for the treatment of skin diseases. Author(s): Frieling U, Luger TA. Source: Clinical and Experimental Dermatology. 2002 October; 27(7): 562-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12464151

Studies

27

•

Novel mechanism of inhibition of cytomegalovirus by the experimental immunosuppressive agent leflunomide. Author(s): Waldman WJ, Knight DA, Lurain NS, Miller DM, Sedmak DD, Williams JW, Chong AS. Source: Transplantation. 1999 September 27; 68(6): 814-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10515382

•

Pancytopenia associated with leflunomide and methotrexate. Author(s): Hill RL, Topliss DJ, Purcell PM. Source: The Annals of Pharmacotherapy. 2003 January; 37(1): 149. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503951

•

Peripheral neuropathy: an unwanted effect of leflunomide? Author(s): Carulli MT, Davies UM. Source: Rheumatology (Oxford, England). 2002 August; 41(8): 952-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12154221

•

Pharmacokinetics of leflunomide in Chinese healthy volunteers. Author(s): Li J, Yao HW, Jin Y, Zhang YF, Li CY, Li YH, Xu SY. Source: Acta Pharmacologica Sinica. 2002 June; 23(6): 551-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12060531

•

Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Author(s): Weinblatt ME, Kremer JM, Coblyn JS, Maier AL, Helfgott SM, Morrell M, Byrne VM, Kaymakcian MV, Strand V. Source: Arthritis and Rheumatism. 1999 July; 42(7): 1322-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403258

•

Potencies of leflunomide and HR325 as inhibitors of prostaglandin endoperoxide H synthase-1 and -2: comparison with nonsteroidal anti-inflammatory drugs. Author(s): Curnock AP, Robson PA, Yea CM, Moss D, Gadher S, Thomson TA, Westwood R, Ruuth E, Williamson RA. Source: The Journal of Pharmacology and Experimental Therapeutics. 1997 July; 282(1): 339-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9223572

28

Leflunomide

•

Prospective, pilot, open-label, short-term study of conversion to leflunomide reverses chronic renal allograft dysfunction. Author(s): Ann Intern Med. 2002 Nov 5;137(9):I42 Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2002 October; 2(9): 867-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416973

•

Purification of human dihydro-orotate dehydrogenase and its inhibition by A77 1726, the active metabolite of leflunomide. Author(s): Bruneau JM, Yea CM, Spinella-Jaegle S, Fudali C, Woodward K, Robson PA, Sautes C, Westwood R, Kuo EA, Williamson RA, Ruuth E. Source: The Biochemical Journal. 1998 December 1; 336 ( Pt 2): 299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9820804

•

Pyrazole bioisosteres of leflunomide as B-cell immunosuppressants for xenotransplantation and chronic rejection: scope and limitations. Author(s): Papageorgiou C, Albert R, Floersheim P, Lemaire M, Bitch F, Weber HP, Andersen E, Hungerford V, Schreier MH. Source: Journal of Medicinal Chemistry. 1998 August 27; 41(18): 3530-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9719606

•

Rheumatoid arthritis and the Arava (leflunomide) controversy. Author(s): Turkoski BB. Source: Orthopaedic Nursing / National Association of Orthopaedic Nurses. 2003 January-February; 22(1): 48-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640952

•

Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study. Author(s): Mladenovic V, Domljan Z, Rozman B, Jajic I, Mihajlovic D, Dordevic J, Popovic M, Dimitrijevic M, Zivkovic M, Campion G, et al. Source: Arthritis and Rheumatism. 1995 November; 38(11): 1595-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7488280

•

Serious liver disease in a patient receiving methotrexate and leflunomide. Author(s): Weinblatt ME, Dixon JA, Falchuk KR. Source: Arthritis and Rheumatism. 2000 November; 43(11): 2609-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11083289

Studies

29

•

Severe pancytopenia after leflunomide in rheumatoid arthritis. Author(s): Auer J, Hinterreiter M, Allinger S, Kirchgatterer A, Knoflach P. Source: Acta Medica Austriaca. 2000; 27(4): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10989684

•

Severe skin reaction after leflunomide and etanercept in a patient with rheumatoid arthritis. Author(s): Soliotis F, Glover M, Jawad AS. Source: Annals of the Rheumatic Diseases. 2002 September; 61(9): 850-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176818

•

Simultaneous determination of leflunomide and its active metabolite, A77 1726, in human plasma by high-performance liquid chromatography. Author(s): Schmidt A, Schwind B, Gillich M, Brune K, Hinz B. Source: Biomedical Chromatography : Bmc. 2003 June; 17(4): 276-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12833393

•

Slowing of disease progression in rheumatoid arthritis patients during long-term treatment with leflunomide or sulfasalazine. Author(s): Larsen A, Kvien TK, Schattenkirchner M, Rau R, Scott DL, Smolen JS, Rozman B, Westhovens R, Tikly M, Oed C, Rosenburg R; European Leflunomide Study Group. Source: Scandinavian Journal of Rheumatology. 2001; 30(3): 135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11469522

•

Successful treatment of sarcoidosis with leflunomide. Author(s): Majithia V, Sanders S, Harisdangkul V, Wilson JG. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 700-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709556

•

Suppression of natural xenophile antibodies with the novel immunomodulating drug leflunomide. Author(s): Ulrichs K, Kaitschick J, Bartlett R, Muller-Ruchholtz W. Source: Transplantation Proceedings. 1992 April; 24(2): 718-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1566498

•

Suppressive effect of combination treatment of leflunomide and methotrexate on chemokine expression in patients with rheumatoid arthritis. Author(s): Ho CY, Wong CK, Li EK, Tam LS, Lam CW. Source: Clinical and Experimental Immunology. 2003 July; 133(1): 132-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823287

30

Leflunomide

•

Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observational study. Author(s): Aletaha D, Stamm T, Kapral T, Eberl G, Grisar J, Machold KP, Smolen JS. Source: Annals of the Rheumatic Diseases. 2003 October; 62(10): 944-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972472

•

T cell aggregation induced through CD43: intracellular signals and inhibition by the immunomodulatory drug leflunomide. Author(s): Layseca-Espinosa E, Pedraza-Alva G, Montiel JL, del Rio R, Fierro NA, Gonzalez-Amaro R, Rosenstein Y. Source: Journal of Leukocyte Biology. 2003 December; 74(6): 1083-93. Epub 2003 September 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972508

•

Teratogen update: reproductive risks of leflunomide (Arava); a pyrimidine synthesis inhibitor: counseling women taking leflunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a child. Author(s): Brent RL. Source: Teratology. 2001 February; 63(2): 106-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11241434

•

The active metabolite of leflunomide, A77 1726, inhibits the production of prostaglandin E(2), matrix metalloproteinase 1 and interleukin 6 in human fibroblastlike synoviocytes. Author(s): Burger D, Begue-Pastor N, Benavent S, Gruaz L, Kaufmann MT, Chicheportiche R, Dayer JM. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 89-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509619

•

The effects of disease-modifying anti-rheumatic drugs on the Health Assessment Questionnaire score. Lessons from the leflunomide clinical trials database. Author(s): Scott DL, Strand V. Source: Rheumatology (Oxford, England). 2002 August; 41(8): 899-909. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12154207

•

The efficacy and safety of leflunomide in patients with active rheumatoid arthritis: a five-year followup study. Author(s): Kalden JR, Schattenkirchner M, Sorensen H, Emery P, Deighton C, Rozman B, Breedveld F. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1513-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794818

Studies

31

•

The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. Author(s): Cherwinski HM, Cohn RG, Cheung P, Webster DJ, Xu YZ, Caulfield JP, Young JM, Nakano G, Ransom JT. Source: The Journal of Pharmacology and Experimental Therapeutics. 1995 November; 275(2): 1043-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7473131

•

The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase. Author(s): Davis JP, Cain GA, Pitts WJ, Magolda RL, Copeland RA. Source: Biochemistry. 1996 January 30; 35(4): 1270-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8573583

•

The mammalian homologue of Prp16p is overexpressed in a cell line tolerant to Leflunomide, a new immunoregulatory drug effective against rheumatoid arthritis. Author(s): Ortlepp D, Laggerbauer B, Mullner S, Achsel T, Kirschbaum B, Luhrmann R. Source: Rna (New York, N.Y.). 1998 August; 4(8): 1007-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9701291

•

The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Author(s): Schattenkirchner M. Source: Immunopharmacology. 2000 May; 47(2-3): 291-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10878295

•

Toward a definition and method of assessment of treatment failure and treatment effectiveness: the case of leflunomide versus methotrexate. Author(s): Wolfe F, Michaud K, Stephenson B, Doyle J. Source: The Journal of Rheumatology. 2003 August; 30(8): 1725-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913927

•

Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Author(s): Strand V, Cohen S, Schiff M, Weaver A, Fleischmann R, Cannon G, Fox R, Moreland L, Olsen N, Furst D, Caldwell J, Kaine J, Sharp J, Hurley F, Loew-Friedrich I. Source: Archives of Internal Medicine. 1999 November 22; 159(21): 2542-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10573044

32

Leflunomide

•

Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine. Author(s): Scott DL, Smolen JS, Kalden JR, van de Putte LB, Larsen A, Kvien TK, Schattenkirchner M, Nash P, Oed C, Loew-Friedrich I; European Leflunomide Study Group. Source: Annals of the Rheumatic Diseases. 2001 October; 60(10): 913-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11557646

•

Treatment of adult-onset Still's disease with leflunomide and chloroquine combination in two patients. Author(s): Pirildar T. Source: Clinical Rheumatology. 2003 May; 22(2): 157. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740686

•

Treatment of Felty's syndrome with leflunomide. Author(s): Talip F, Walker N, Khan W, Zimmermann B. Source: The Journal of Rheumatology. 2001 April; 28(4): 868-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11327265

•

Treatment of severe psoriasis and psoriatic arthritis with leflunomide. Author(s): Reich K, Hummel KM, Beckmann I, Mossner R, Neumann C. Source: The British Journal of Dermatology. 2002 February; 146(2): 335-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903256

•

Treatment options for rheumatoid arthritis: celecoxib, leflunomide, etanercept, and infliximab. Author(s): Luong BT, Chong BS, Lowder DM. Source: The Annals of Pharmacotherapy. 2000 June; 34(6): 743-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10860137

•

Treatment with leflunomide slows radiographic progression of rheumatoid arthritis: results from three randomized controlled trials of leflunomide in patients with active rheumatoid arthritis. Leflunomide Rheumatoid Arthritis Investigators Group. Author(s): Sharp JT, Strand V, Leung H, Hurley F, Loew-Friedrich I. Source: Arthritis and Rheumatism. 2000 March; 43(3): 495-505. Erratum In: Arthritis Rheum 2000 June; 43(6): 1345. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10728741

Studies

33

•

Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Utilization of Leflunomide in the Treatment of Rheumatoid Arthritis Trial Investigator Group. Author(s): Cohen S, Cannon GW, Schiff M, Weaver A, Fox R, Olsen N, Furst D, Sharp J, Moreland L, Caldwell J, Kaine J, Strand V. Source: Arthritis and Rheumatism. 2001 September; 44(9): 1984-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592358

•

Unproven hypothesis that leflunomide is better than methotrexate as measured by magnetic resonance imaging: comment on the article by Reece et al. Author(s): Schnarr S, Hulsemann JL, Zeidler HK. Source: Arthritis and Rheumatism. 2003 January; 48(1): 270-1; Author Reply 271. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528131

•

Use of leflunomide in human renal transplantation. Author(s): Pascual J, Orte J, Marcen R, Burgos J, Ortuno J. Source: Transplantation. 2001 November 27; 72(10): 1709. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726839

•

Vasculitis occurring during leflunomide therapy. Author(s): Holm EA, Balslev E, Jemec GB. Source: Dermatology (Basel, Switzerland). 2001; 203(3): 258-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701983

•

Weekly dose of leflunomide for the treatment of refractory rheumatoid arthritis: an open pilot comparative study. Author(s): Jakez-Ocampo J, Richaud-Patin Y, Simon JA, Llorente L. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 May; 69(3): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102278

•

Weekly leflunomide as monotherapy for recent-onset rheumatoid arthritis. Author(s): Jakez-Ocampo J, Richaud-Patin Y, Granados J, Sanchez-Guerrero J, Llorente L. Source: Arthritis and Rheumatism. 2004 February 15; 51(1): 147-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872469

•

Which HAQ is best? A comparison of the HAQ, MHAQ and RA-HAQ, a difficult 8 item HAQ (DHAQ), and a rescored 20 item HAQ (HAQ20): analyses in 2,491 rheumatoid arthritis patients following leflunomide initiation. Author(s): Wolfe F. Source: The Journal of Rheumatology. 2001 May; 28(5): 982-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11361226

35

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

Finding Nutrition Studies on Leflunomide The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “leflunomide” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

36

Leflunomide

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

Cell-specific inhibition of inducible nitric oxide synthase activation by leflunomide. Author(s): Institute of Microbiology and Immunology, University of Belgrade, Belgrade, Yugoslavia. Source: Jankovic, V Samardzic, T Stosic Grujicic, S Popadic, D Trajkovic, V CellImmunol. 2000 February 1; 199(2): 73-80 0008-8749

•

Diabetic rats transplanted with adult porcine islets and immunosuppressed with cyclosporine A, mycophenolate mofetil, and leflunomide remain normoglycemic for up to 100 days. Author(s): Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden. Source: Wennberg, L Song, Z Bennet, W Zhang, J Nava, S Sundberg, B Bari, S Groth, C G Korsgren, O Transplantation. 2001 April 27; 71(8): 1024-33 0041-1337

•

Effect of RS61443 in combination with leflunomide or FK506 on rat heart allograft survival. Author(s): Transplantation Microsurgery Laboratory, Queen Elizabeth Hospital and Medical Center, Edgbaston, Birmingham, UK. Source: Antoniou, E DeRoover, A Nishimura, Y Howie, A J McMaster, P D'Silva, M Transpl-Int. 1996; 9 Suppl 1S331-3 0934-0874

•

Effects of long-term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma. Author(s): Division of Clinical Sciences, TVW Telethon Institute for Child Health Research, West Perth, Western Australia. Source: Uhlig, T Cooper, D Eber, E McMenamin, C Wildhaber, J H Sly, P D Clin-ExpAllergy. 1998 June; 28(6): 758-64 0954-7894

•

Flow cytometric analysis of the molecular mechanisms of immunosuppressive action of the active metabolite of leflunomide and its malononitrilamide analogues in a novel whole blood assay. Author(s): Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA 94305-5247, USA. Source: Slauson, S D Silva, H T Sherwood, S W Morris, R E Immunol-Lett. 1999 April 15; 67(3): 179-83 0165-2478

•

Immunosuppression with cyclosporin A in combination with leflunomide and mycophenolate mofetil prevents rejection of pig-islets transplanted into rats. Author(s): Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden. Source: Wennberg, L Wallgren, A C Sundberg, B Rafael, E Zhu, S Liu, J Tibell, A Karlsson Parra, A Groth, C G Korsgren, O Transplant-Proc. 1996 April; 28(2): 819 00411345

•

Immunosuppressive effect of RS-61443 on rat cardiac allograft survival in combination with leflunomide or FK 506. Author(s): Transplantation Microsurgery Laboratory, Queen Elizabeth Hospital, Edgbaston, UK. Source: D'Silva, M Antoniou, E DeRoover, A Nishimura, Y Howie, A McMaster, P Transplant-Proc. 1996 April; 28(2): 930-1 0041-1345

Nutrition

37

•

In vitro and in vivo antitumor activity of a novel immunomodulatory drug, leflunomide: mechanisms of action. Author(s): Department of General Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. [email protected] Source: Xu, X Shen, J Mall, J W Myers, J A Huang, W Blinder, L Saclarides, T J Williams, J W Chong, A S Biochem-Pharmacol. 1999 November 1; 58(9): 1405-13 0006-2952

•

In vivo mechanism by which leflunomide controls lymphoproliferative and autoimmune disease in MRL/MpJ-lpr/lpr mice. Author(s): Department of General Surgery, Rush Medical College, Chicago, IL 60612, USA. Source: Xu, X Blinder, L Shen, J Gong, H Finnegan, A Williams, J W Chong, A S JImmunol. 1997 July 1; 159(1): 167-74 0022-1767

•

Inhibition of anti-CD3 antibody-induced mouse T cell activation by pentoxifylline in combination with rapamycin or A77 1726 (leflunomide). Author(s): Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. Source: Richard, M Hoskin, D W Int-J-Immunopharmacol. 1998 Apr-May; 20(4-5): 241-52 0192-0561

•

Inhibition of murine IgE and immediate cutaneous hypersensitivity responses to ovalbumin by the immunomodulatory agent leflunomide. Author(s): Clinical Research Unit, Department of Dermatology, Johannes GutenbergUniversity, Mainz, Germany. Source: Jarman, E R Kuba, A Montermann, E Bartlett, R R Reske Kunz, A B Clin-ExpImmunol. 1999 February; 115(2): 221-8 0009-9104

•

Inhibition of smooth muscle cell proliferation in vitro by leflunomide, a new immunosuppressant, is antagonized by uridine. Author(s): Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA 94305-5247, USA. Source: Nair, R V Cao, W Morris, R E Immunol-Lett. 1995 December; 48(2): 77-80 01652478

•

Leflunomide (HWA 486) and its analog suppress T- and B-cell proliferation in vitro, acute rejection, ongoing rejection, and antidonor antibody synthesis in mouse, rat, and cynomolgus monkey transplant recipients as well as arterial intimal thickening after balloon catheter injury. Author(s): Department of Cardiothoracic Surgery, Stanford University School of Medicine, CA 94305-5247. Source: Morris, R E Huang, X Cao, W Zheng, B Shorthouse, R A Transplant-Proc. 1995 February; 27(1): 445-7 0041-1345

•

Leflunomide induces apoptosis of thymocytes and T-cell hybridoma: differences in sensitivity and signaling pathways. Author(s): Institute of Medical Research, Military Medical Academy, Belgrade, Yugoslavia. Source: Colic, M Popovic, P Vucevic, D Dimitrijevic, M Transplant-Proc. 2001 May; 33(3): 2344-6 0041-1345

•

Leflunomide inhibits cytokine-induced DNA synthesis of rabbit synovial cells in culture. Author(s): Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.

38

Leflunomide

Source: Ju, D W Zheng, Q Y Wang, H B Fang, J Zhongguo-Yao-Li-Xue-Bao. 1994 May; 15(3): 223-6 0253-9756 •

Leflunomide, a novel immunomodulating agent, prevents the development of allergic sensitization in an animal model of allergic asthma. Author(s): Division of Clinical Sciences, TVW Telethon Institute for child Health Research, Perth, Western Australia. Source: Eber, E Uhlig, T McMenamin, C Sly, P D Clin-Exp-Allergy. 1998 March; 28(3): 376-84 0954-7894

•

Oral administration of leflunomide (HWA486) results in prominent suppression of immunoglobulin E formation in a rat type 1 allergy model. Author(s): Autoimmune Diseases Project, Discovery Research Laboratories, Hoechst Japan, Ltd., Saitama, [email protected] Source: Mizushima, Y Amano, Y Kitagawa, H Ogata, K J-Pharmacol-Exp-Ther. 1999 February; 288(2): 849-57 0022-3565

•

Prevention of experimental autoimmune diabetes in mice by treatment with leflunomide. Author(s): Institute for Biological Research, University of Belgrade, Yugoslavia. Source: Stosic Grujicic, S Dimitrijevic, M Bartlett, R R Transplant-Proc. 1998 December; 30(8): 4132-3 0041-1345

•

Tacrolimus enhances the immunosuppressive effect of cyclophosphamide but not that of leflunomide or mycophenolate mofetil in a model of discordant liver xenotransplantation. Author(s): Thomas E. Starzl Transplantation Institute, Pittsburgh, PA 15261, USA. Source: Miki, T Goller, A Rao, A Wang, X Yin, W Y Tandin, A Fung, J J Starzl, T E Valdivia, L A Transplant-Proc. 1998 June; 30(4): 1091-2 0041-1345

•

Three leflunomide metabolite analogs. Author(s): Department of Structural Biology (Drug Discovery Program), Parker Hughes Institute, 2665 Long Lake Road, Suite 330, St Paul, MN 55113, USA. [email protected]. Source: Ghosh, S Jennissen, J D Zheng, Y Uckun, F M Acta-Crystallogr-C. 2000 October; 56 ( Pt 10)1254-7 0108-2701

•

Triple drug treatment with cyclosporine, leflunomide and mycophenolate mofetil prevents rejection of pig islets transplanted into rats and primates. Author(s): Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden. Source: Wennberg, L Groth, C G Tibell, A Zhu, S Liu, J Rafael, E Soderlund, J Biberfeld, P Morris, R E Karlsson Parra, A Korsgren, O Transplant-Proc. 1997 August; 29(5): 2498 0041-1345

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

Nutrition

39

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

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/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to leflunomide; 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: •

Food and Diet Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.com

41

CHAPTER 3. CLINICAL TRIALS AND LEFLUNOMIDE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning leflunomide.

Recent Trials on Leflunomide The following is a list of recent trials dedicated to leflunomide.8 Further information on a trial is available at the Web site indicated. •

Leflunomide to Treat Uveitis Condition(s): Uveitis Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will investigate the safety and effectiveness of the drug Leflunomide to treat uveitis-an inflammation of the eye caused by an immune system abnormality. Leflunomide suppresses immune system activity and has been shown to control autoimmune diseases, such as arthritis (joint inflammation), in animals. It has also improved symptoms in patients with rheumatoid arthritis, and the Food and Drug Administration has approved it for treating patients with this disease. Eye and joint inflammation may have similar causes, and medicines for arthritis often help patients with eye inflammation. This study will examine whether Leflunomide can help patients with uveitis. Patients with uveitis who are not responding well to steroid treatment and patients who have side effects from other medicines used to treat uveitis (such as cyclosporine, cyclophosphamide, methotrexate or azathioprine) or have refused treatment because of possible side effects of these medicines may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood test and eye examination. The eye exam includes a check of vision and eye pressure, examination of the back of the eye (retina) with an ophthalmoscope and the front of the eye with a microscope. They will also undergo a procedure called fluorescein angiography to look at the blood vessels of the eye. A dye called sodium fluorescein is

8

These are listed at www.ClinicalTrials.gov.

42

Leflunomide

injected into the bloodstream through a vein. After the dye reaches the blood vessels of the eye, photographs are taken of the retina. Study participants will be divided into two groups. One group will take 100 milligrams of Leflunomide once a day for 3 days and then 20 milligrams once a day for 6 months. The other group will take a placebo-a pill that looks like the Leflunomide pill but doesn't contain the medicine. All patients in both groups will also take prednisone. Patients will have follow-up examinations at weeks 1, 4, 8, 12, 16, and 24 (6 months) of the study. Each follow-up visit will include a repeat of the screening exams and an evaluation of side effects or discomfort from the medicine. Those who do well and want to continue their assigned treatment after 6 months can continue that treatment for another 6 months and will have follow-up exams at months 9 and 12. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001863

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “leflunomide” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

•

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

Clinical Trials 43

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

45

CHAPTER 4. PATENTS ON LEFLUNOMIDE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “leflunomide” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on leflunomide, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Leflunomide By performing a patent search focusing on leflunomide, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

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

46

Leflunomide

example of the type of information that you can expect to obtain from a patent search on leflunomide: •

Analogues of the active metabolite of leflunomide Inventor(s): Bertolini; Giorgio (Cinisello Balsamo, IT), Biffi; Mauro (Cinisello Balsamo, IT), Leoni; Flavio (Cinisello Balsamo, IT), Marchetti; Maria Letizia (Cinisello Balsamo, IT), Mascagni; Paolo (Cinisello Balsamo, IT), Mizrahi; Jacques (Cinisello Balsamo, IT), Somenzi; Flavio (Cinisello Balsamo, IT) Assignee(s): Italfarmaco S.p.a. (milan, It) Patent Number: 5,905,090 Date filed: April 29, 1998 Abstract: Analogues of the active metabolite of leflunomide, and to the use thereof as immunosuppressive and/or antinflammatory agents. Excerpt(s): The present invention relates to analogues of the active metabolite of leflunomide, and to the use thereof as immunosuppressive and/or antinflammatory agents. Leflunomide, i.e. ›5-methyl-N-(4-trifluoromethylphenyl)isossazole-4carboxamide), is a molecule described in EP-B-0 013 376 as an antinflammatory, analgesic and antipyretic agent in the treatment of rheumatoid arthritis, as it also has immunosuppressive activity. Ann. Rep. Med. Chem., 18, 177 (1983) states that its activity is actually exerted by a metabolite, A-77-1726 ›N-(4-trifluoromethylphenyl)-1cyano-2-ketopropyl-carboxamide!, in particular by the.beta.-ketonitrile system (which is liable to keto-enol tautomerism) contained therein. In fact, when replacing the cyano group with an ester group, the activity dramatically decreases or even disappears ›(J. Chem. Soc. Perkin Trans, 1, 2203 (1992)!. Now it has surprisingly been found that some analogues of the metabolite A-77-1726, although lacking in the.beta.-ketonitrile system, exert antinflammatory and immunosuppressive activities, which activities are, in some molecules of the class object of the present invention, separated. Web site: http://www.delphion.com/details?pn=US05905090__

•

Method of treating a patient by parenteral administration of a lipophilic compound Inventor(s): Schwartz; Donna Pruess (San Mateo, CA), Shawver; Laura Kay (San Francisco, CA) Assignee(s): Sugen, Inc. (redwood City, Ca) Patent Number: 6,335,356 Date filed: March 1, 2000 Abstract: The present invention features pharmaceutical formulations containing a lipophilic compound such as leflunomide. The lipophilic compound is solubilized in solution containing alcohol and a surfactant. The solubilized compound can then be further dissolved in a pharmaceutically acceptable aqueous solution, such as WFI (water for injection), D5W (5% dextrose in water) or D5W 1/2 N saline, to form a pharmaceutical formulation suitable for patient administration. The formulation is preferably used for parenteral administration. Excerpt(s): The present invention features pharmaceutical formulations containing lipophilic compounds. Various methods are available for administering therapeutic

Patents 47

agents into a patient. Such methods include, parenteral, oral, ocular, nasal, topical, and transmucosal administration. Variations of these different types of administrations exist. For example, parenteral administration includes intravenous, subcutaneous, intraperitoneal, intramuscular, and intramedullary injection. The chosen mode of administration should take into account the nature of the therapeutic compound and the illness being treated. Lipophilic compounds are non-polar and have low solubility in water. Different techniques concerned with solubilizing lipophilic compounds include those described by Praveen et al., U.S. Pat. No. 5,314,685, and Fernades et al., U.S. Pat. No. 4,992,271. Web site: http://www.delphion.com/details?pn=US06335356__ •

Processes for making- and a new crystalline form of- leflunomide Inventor(s): Aronhime; Judith (Rechovot, IL), Avrutov; Ilya (Bat Hefer, IL), Gershon; Neomi (Kfar Saba, IL) Assignee(s): Teva Pharmaceutical Industries Ltd. (petah Tiqva, Il) Patent Number: 6,610,718 Date filed: December 14, 2000 Abstract: New leflunomide Form III is disclosed, along with processes for preparing it. The present invention also provides an economic process for preparing leflunomide Form II and a process for preparing leflunomide Form I from leflunomide Form III. Pharmaceutical compositions and dosage forms containing the new form and methods of using them for the treatment of rheumatoid arthritis are also disclosed. Excerpt(s): The present invention relates to a novel leflunomide Form III and to processes for making leflunomide Forms I, II and III. is an inhibitor of pyrimidine biosynthesis with antiproliferative activity and is approved in the United States for treatment of rheumatoid arthritis. The present invention relates to polymorphic forms of leflunomide. Polymorphism is the property of some molecules to adopt more than one crystalline form in the solid state. A single molecule may give rise to a variety of solids having distinct physical properties that can be measured in a laboratory like its thermal behavior--e.g. melting point and differential scanning calorimetry ("DSC") thermogram-dissolution rate, flowability, X-ray diffraction pattern, infrared absorption spectrum and NMR spectrum. The differences in the physical properties of polymorphs result from the orientation and intermolecular interactions of adjacent molecules in the bulk solid. Accordingly, polymorphs are distinct solids sharing the same molecular formula which may yet have distinct advantageous and/or disadvantageous physical properties compared to other forms in the polymorph family. Web site: http://www.delphion.com/details?pn=US06610718__

48

•

Leflunomide

Tumor necrosis factor antagonists for the treatment of neurological disorders Inventor(s): Tobinick; Arthur Jerome (100 UCLA Medical Plz., Suite 205, Los Angeles, CA 90024-6903), Tobinick; Edward L. (100 UCLA Medical Plz., Suite 205, Los Angeles, CA 90024-6903) Assignee(s): None Reported Patent Number: 6,015,557 Date filed: March 23, 1999 Abstract: A method for inhibiting the action of TNF for treating neurological conditions in a human by administering a TNF antagonist for reducing damage to neuronal tissue or for modulating the immune response affecting neuronal tissue of the human. The TNF antagonist administered is selected from the group consisting of etanercept and infliximab. The TNF antagonist is administered subcutaneously, intravenously, intrathecally, or intramuscularly.Methotrexate or Leflunomide may be administered concurrently with the TNF antagonist for demyelinating diseases and certain other neurological disorders. Excerpt(s): The present invention relates to tumor necrosis factor (TNF) antagonists or TNF blockers for the treatment of neurological disorders, trauma, injuries or compression; or demyelinating neurological disorders, including multiple sclerosis. More particularly, the TNF antagonists or TNF blockers, with or without the concurrent administration of methotrexate or Leflunomide, are used in a new treatment of these disorders by inhibiting the action of TNF in the cells of the human body. The use of these TNF antagonists or TNF blockers with methotrexate or Leflunomide results in the amelioration of these neurological conditions. Neurological disorders due to demyelinating disease (e.g. multiple sclerosis), immune disease, inflammation, trauma, or compression, occur in different clinical forms depending upon the anatomic site and the cause and natural history of the physiological problem. Common to all of these disorders is the fact that they can cause permanent neurological damage, that damage can occur rapidly and be irreversible, and that current treatment of these conditions is unsatisfactory, often requiring surgery and/or the use of pharmacologic agents, which are often not completely successful. These neurological conditions include acute spinal cord trauma, spinal cord compression, spinal cord hematoma, cord contusion (these cases are usually traumatic, such as motorcycle accidents or sports injuries); nerve compression, the most common condition being a herniated disc causing sciatic nerve compression, neuropathy, and pain; but also including cervical disc herniation, causing nerve compression in the neck; carpal tunnel syndrome (non-RA); acute or chronic spinal cord compression from cancer (this is usually due to metastases to the spine, such as from prostate, breast or lung cancer); autoimmune disease of the nervous system; and demyelinating diseases, the most common condition being multiple sclerosis. Web site: http://www.delphion.com/details?pn=US06015557__

•

Use of leflunomide for inhibiting interleukin 8 Inventor(s): Bartlett; Robert R. (Darmstadt, DE), Weithmann; Klaus U. (Hofheim, DE) Assignee(s): Hoechst Aktiengesellschaft (frankfurt AM Main, De) Patent Number: 5,547,971 Date filed: March 28, 1995

Patents 49

Abstract: The use of leflunomide for inhibiting interleukin 8 N-(4Trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide is an effective compound for preventing and treating disorders in which interleukin 8 is involved. It is used as a pharmaceutical. Excerpt(s): Leflunomide (see formula, N-(4-trifluoromethylphenyl)-5-methylisoxazole-4carboxamide) is already known as a chemical compound (EP 0013376, EP 0217206, U.S. Pat. Nos. 4,351,841, 4,965,276). Axton et al., J. Chem. Soc. Perkin Trans. 1 (1992) 2203 ff. also describe how leflunomide does not represent the active principle and that, instead, this primary metabolite exhibits the biological effects. It has been possible to demonstrate both in the literature (Bartlett et al., Agents and Actions, 32 (1991) 10-21) and in our own experiments that the therapeutic effects described in more detail below cannot be obtained by administering the leflunomide metabolite. Thus, it was found, in accordance with the invention, that leflunomide exerts a strong inhibitory effect on the synthesis and liberation of cytokines from human blood cells, whereas the leflunomide metabolite does not exhibit this advantageous effect. Web site: http://www.delphion.com/details?pn=US05547971__ •

Use of leflunomide to control and reverse chronic allograft rejection Inventor(s): Williams; James (655 Superior, Oak Park, IL 60302) Assignee(s): None Reported Patent Number: 5,624,946 Date filed: July 5, 1994 Abstract: The present invention relates to methods of controlling or reversing chronic rejection of allografts in a transplantation patient by administering leflunomide product alone, or in combination with one or more immunosuppressive agents selected from the group consisting of Cyclosporine A, FK506, rapamycin and corticosteroids. The invention also relates to methods of preventing or controlling acute and chronic rejection of xenografts in a transplantation patient by administering leflunomide product alone, or in combination with one or more immunosuppressive agents selected from the group consisting of Cyclosporine A, FK506, rapamycin and corticosteroids. Excerpt(s): Organ transplants of liver, kidney, heart and lung are now regularly performed as treatment for end-stage organ disease. Allograft (same species donor and recipient) as well as xenograft (different species donor and recipient) transplants have been performed. In 1989 over 14,000 patients received allografts in the United States alone. Transplant outcome has progressively improved with the development of refinements in tissue typing, surgical techniques, and more effective immunosuppressive treatments. However, because of problems with long-term chronic rejection, organ transplantation is not yet a permanent solution to irreversible organ disease. Chronic rejection, which manifests as progressive and irreversible damage to the graft from attack due to host immune responses, is the leading cause of organ transplant loss after the first postoperative year. A significant proportion of grafts, regardless of type, deteriorate and fail within the first several months or years after transplant despite administration of maintenance immunosuppression. Although the pace of graft destruction varies from patient to patient, essentially all heart or kidney transplants of cadaveric origin eventually succumb to chronic rejection. This persistent rate of decline of long-functioning grafts has remained constant over time, despite improvements in immunosuppressive therapy and in overall care for graft recipients.

50

Leflunomide

The half-life of a kidney transplant after the first year is seven years and has not changed with use of Cyclosporine A or anti-lymphocyte antibodies. In multicenter data from North America reported in 1988, less than half of the kidney cadaveric grafts continued to function at six years post-transplant although 80% behave satisfactorily at the end of the first year. There is a similar rate of decline for other types of organ grafts; the incidence of coronary arteriosclerosis in heart grafts reaches 50% before five years, resulting in a 25% mortality rate, and 40-50% of liver allografts no longer function at 5 years after transplant. This somewhat lower rate of chronic rejection for liver may be due to lower immunogenicity of liver tissue. The mechanism underlying chronic rejection is poorly understood. Various aspects of host immune responses have been implicated in the phenomenon, and its etiology may be multifaceted. Chronic rejection is inexorable and uncontrollable because there is no known effective treatment. Thus, there continues to exist a need for a treatment effective in preventing, controlling or reversing the chronic rejection of organ transplants. Web site: http://www.delphion.com/details?pn=US05624946__

Patent Applications on Leflunomide As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to leflunomide: •

Anti-viral uses of leflunomide products Inventor(s): Chong, Anita; (Chicago, IL), Waldman, W. James; (Dublin, OH), Williams, James W.; (Oak Park, IL) Correspondence: Marshall O'toole Gerstein; Murray & Borun; 6300 Sears Tower; 233 South Wacker Drive; Chicago; IL; 60606-6402; US Patent Application Number: 20030114507 Date filed: April 6, 2000 Abstract: The present invention relates to anti-viral uses of leflunomide product, alone or in combination with other anti-viral agents, or in combination with a pyrimidine such as uridine. Excerpt(s): This application claims priority of U.S. provisional application No. 60/077,552 filed Mar. 11, 1998. The present invention relates generally to novel anti-viral materials and methods involving leflunomide products. [Stecher et al., Ann. Report Med Chem., 18:171-179 (1983).] Leflunomide originated from a series of compounds that were designed as agricultural herbicides by scientists at Hoechst AG. It was later found to have anti-inflammatory and immunosuppressive activity, and it has been evaluated in animal models of autoimmune disease and transplant rejection. The metabolite exhibits two mechanisms of action: inhibition of protein tyrosine kinase activity, and inhibition of dihydroorotate dehydrogenase, a key enzyme in the biosynthesis of pyrimidine nucleotide triphosphates. See generally Silva et al., Am. J. Med. Sci., 313(5):289-301 (1997) and Principles of Drug Development in Transplantation and Autoimmunity, Lieberman and Mukherjee, eds., R. G. Landes Co., Austin (1996).

10

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

Patents 51

The drug is well tolerated in animals and man and is currently under clinical investigation in human patients with advanced rheumatoid arthritis. No anti-viral activity has previously been reported for leflunomide or its metabolite. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for systhesizing leflunomide Inventor(s): Avrutov, Ilya; (Bat Hefer, IL), Gershon, Neomi; (Kfar Saba, IL), Liberman, Anita; (Ramat Aviv, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020022646 Date filed: February 8, 2001 Abstract: A process for synthesizing leflunomide from 5-methylisoxazole-4-carboxylic acid and 4-trifluoromethylaniline is provided. Further provided is the leflunomide prepared by the inventive process, which is substantially free of difficult-to-separate impurities often found in leflunomide prepared by known methods, including N-(4trifluoromethylphenyl)-2-cyano-- 3-hydroxycrotonamide, 5-methyl-N-(4-methylphenyl)isoxazole-4-carboxamide and N-(4-trifluoromethylphenyl)-3-methyl-isoxazole-4carboxamide. The invention further provides pharmaceutical compositions and dosage forms containing highly pure leflunomide and methods of treating disease using the leflunomide. Excerpt(s): The present invention relates to the anti-proliferative compound leflunomide and to a process for synthesizing leflunomide. Pyrimidine biosynthesis is an essential function of cells. It is the biosynthetic pathway to the DNA base constituents of uracil, cytosine and thymine and produces precursors of molecules used in the synthesis of ATP, several cofactors and other important cell components. Uracil, cytosine and thymine are essential to DNA replication during cell proliferation. [Prescott, L. M.; Harley, J. P.; Klein D. A. Microbiology 203 (4th ed., McGraw Hill, 1999)]. Many diseases are caused by or are aggravated by the failure of natural mechanisms to regulate cell proliferation, such as cancer and some inflammatory diseases like rheumatoid arthritis. Most cancer therapies attempt to suppress the proliferation of rapidly dividing cells. Disruption of the pyrimidine biosynthesis pathway is one way to suppress proliferation of rapidly dividing cells because the disruption interferes with the cell's ability to replicate DNA. Leflunomide has been shown to be effective for treatment of the inflammatory disease rheumatoid arthritis although the mechanism by which it causes this particular therapeutic effect is not completely understood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Micronized leflunomide Inventor(s): Avrutov, Ilya; (Bat Hefer, IL) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020077485 Date filed: August 14, 2001 Abstract: The present invention relates to leflunomide having relatively small particles, and corresponding relatively large surface area. In one embodiment, the invention

52

Leflunomide

relates to leflunomide and formulations containing leflunomide having a mean particle diameter of less than 200 micrometers. Excerpt(s): The present application claims benefit of U.S. provisional application Ser. No. 60/225,372, filed Aug. 14, 2000, which is incorporated by reference. This invention relates to micronized leflunomide and to the preparation thereof. is approved, under the trademark ARAVA.RTM., by the U.S. Food and Drug Administration, for the treatment of rheumatoid arthritis. Leflunomide is a pyrimidine synthase inhibitor with antiproliferative activity. Leflunomide metabolizes to 2-cyano-3-hydroxy-N-[4(trifluoromet- hyl) phenyl)]-(2E)-butenamide in the human body. The metabolite 2cyano-3-hydroxy -N-[4-(trifluoromethyl)phenyl)]-(2E)-butenamide is the active agent that inhibits pyrimidine synthase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel processes for making- and a new crystalline form of- leflunomide Inventor(s): Aronhime, Judith; (Rechovot, IL), Avrutov, Ilya; (Bat Hefer, IL), Gershon, Naomi; (Kfar Saba, IL) Correspondence: Steven J. Lee; Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20010031878 Date filed: December 14, 2000 Abstract: New leflunomide Form III is disclosed, along with processes for preparing it. The present invention also provides an economic process for preparing leflunomide Form II and a process for preparing leflunomide Form I from leflunomide Form III. Pharmaceutical compositions and dosage forms containing the new form and methods of using them for the treatment of rheumatoid arthritis are also disclosed. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn. 119(e) of U.S. Provisional Patent Application No. 60/171228, filed Dec. 16, 1999, U.S. Provisional Patent Application No. 60/202416, file May 8, 2000, U.S. Provisional Patent Application No. 60/171237, filed Dec. 16, 1999, and U.S. Provisional Patent Application No. 60/182647, filed Feb. 15, 2000. The present invention relates to a novel leflunomide Form III and to processes for making leflunomide Forms I, II and III. is an inhibitor of pyrimidine biosynthesis with antiproliferative activity and is approved in the United States for treatment of rheumatoid arthritis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Treatments for immune-mediated ear disorders Inventor(s): Choi, Hyon K.; (Lexington, MA), Poe, Dennis S.; (Chestnut Hill, MA), Rahman, Mahboob U.; (Sharon, MA) Correspondence: Clark & Elbing Llp; 176 Federal Street; Boston; MA; 02110-2214; US Patent Application Number: 20020044920 Date filed: March 27, 2001 Abstract: Disclosed herein are methods for treating immune-mediated ear disorders, such as IMCVDs, or their symptoms, involving administration of a therapeutically-

Patents 53

effective amount of a TNF antagonist, such as etanercept or infliximab, or a therapeutically-effective amount of a pyrimidine synthesis inhibitor, such as leflunomide. Excerpt(s): This application claims the benefit of the filing date of U.S. provisional patent application No. 60/192,299, filed Mar. 27, 2000. This invention relates to methods for treating immune-mediated ear disorders. Immune mediated ear disorders, such as immune-mediated cochlear or vestibular disorders (IMCVD), continue to present a management challenge to the otolaryngologist. These disorders represent a syndrome of sensorineural hearing loss, often associated with vertigo, tinnitus, and aural fullness believed to be due to an autoimmune mechanism. The sequelae of IMCVDs include devastating disabilities, such as profound deafness and serious vestibular dysfunction. Immunosuppressive drugs like cyclophosphomide and anti-rheumatic agents like methotrexate are employed for IMCVD, but are associated with variable efficacy, slow onset of effects, and sometimes serious toxicity. 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 leflunomide, 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 “leflunomide” (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 leflunomide. You can also use this procedure to view pending patent applications concerning leflunomide. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

55

CHAPTER 5. BOOKS ON LEFLUNOMIDE Overview This chapter provides bibliographic book references relating to leflunomide. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on leflunomide include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “leflunomide” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on leflunomide: •

Conquering Rheumatoid Arthritis: The Latest Breakthroughs and Treatments Source: Amherst, NY: Prometheus Books. 2001. 255 p. Contact: Available from Prometheus Books. 59 John Glenn Drive, NY 14228-2197. (716) 691-0133 or (800) 421-0351. Website: www.prometheusbooks.com. PRICE: $20.00. ISBN: 1573928860. Summary: This book for patients describes the origins, disease course, and treatment of rheumatoid arthritis (RA). Rheumatoid arthritis affects over two million Americans. It is three times more common in women than men and becomes increasingly common in people as they age. RA is an inflammatory disease of the synovium, or lining of a joint, that results in pain, stiffness, swelling, joint damage, and loss of function in the joints. Chapters discuss the body's immune system; the anatomy of the synovial joints; the system by which the body's immune system attacks these joints; the genetic origins of RA and gene therapy; stem cell research and therapy; traditional treatments for RA

56

Leflunomide

including NSAIDS, DMARDS, and steroids; new medications including etanercept, COX-1 and COX-2 enzymes, leflunomide, and infliximab; clinical trials; and potential therapies. Appendices include related websites and a glossary. 14 figures. •

Immunosuppressive Drugs: Developments in Anti-Rejection Therapy Source: London, England: Edward Arnold. 1994. 235 p. Contact: Available from Little, Brown and Company. Order Department, 200 West Street, Waltham, MA 02154. (800) 343-9204. PRICE: $67.50 (as of 1995). ISBN: 0340569514. Summary: This medical textbook reviews recent developments in antirejection therapy with immunosuppressive drugs. Seventeen chapters, authored by experts in the field, cover conventional immunosuppressive drugs; the molecular actions of cyclosporin A (CsA), FK506, and rapamycin; the pharmacokinetics and monitoring of CsA; the cellular immunobiology of CsA; the influence of CsA on graft rejection; pharmacokinetics and monitory of FK506; the influence of FK506 on lymphocyte responses in vitro and in vivo; the influence of FK506 on experimental and on clinical transplantation; the immunosuppressive role of rapamycin in allograft rejection; the promotion of cell chimerism by immunosuppressive drugs; and the mode of action and effects on graft rejection of mycophenolate mofetil (RS-61443), mizoribine (Bredinin), brequinar sodium, deoxyspergualin, leflunomide, and SK and F 105685. Each chapter includes extensive references; a subject index concludes the volume.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “leflunomide” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “leflunomide” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “leflunomide” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Leflunomide: Proceedings of the Vienna Symposium, 12 October 1993 by R. R. Bartlett; ISBN: 3764351500; http://www.amazon.com/exec/obidos/ASIN/3764351500/icongroupinterna

Chapters on Leflunomide In order to find chapters that specifically relate to leflunomide, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and leflunomide using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “leflunomide” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on leflunomide:

Books

•

57

Immunosuppressive Strategies for the Pediatric Population Source: in Tejani, A.H. and Fine, R.N., eds. Pediatric Renal Transplantation. New York, NY: Wiley-Liss. 1994. p. 23-49. Contact: Available from John Wiley and Sons, Inc. 1 Wiley Drive, Somerset, NJ 088751272. (800) 225-5945. PRICE: $99.95 (as of 1995). ISBN: 0471591203. Summary: In this chapter, from a medical text about pediatric renal transplantation, the authors discuss immunosuppressive strategies for the pediatric population. Topics include a brief history of immunosuppressive; mechanisms of immunosuppressive drug actions, including corticosteroids, azathioprine, cyclophosphamide, polyclonal antilymphocyte preparations, monoclonal antibodies, and cyclosporine; cyclosporine therapy in the pediatric population; algorithms of drug therapy; and new immunosuppressive agents, including cyclosporine G and IMM-125, FK506, rapamycin, new antiproliferative agents, 15-deoxyspergualin, new monoclonal antibodies, and leflunomide (HWA 486). The authors stress that a rigorous pharmacokinetic approach to the evaluation of multidrug combinations using mathematical models are likely to yield highly selective but nontoxic immunosuppressive regimens. 4 figures. 1 table. 285 references.

59

CHAPTER 6. PERIODICALS AND NEWS ON LEFLUNOMIDE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover leflunomide.

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

Leflunomide is safe, effective for rheumatoid arthritis Source: Reuters Medical News Date: January 29, 2004

•

Aventis says five die in Japan after taking Arava for rheumatoid arthritis Source: Reuters Medical News Date: January 28, 2004

60

Leflunomide

•

Adherence to leflunomide might improve with lower starting dose Source: Reuters Medical News Date: December 18, 2003

•

Aventis warns of liver side effects of Arava drug Source: Reuters Medical News Date: November 21, 2003

•

Leflunomide dosing for RA inadequate for some patients Source: Reuters Medical News Date: September 30, 2003

•

Beneficial effects of leflunomide for rheumatoid arthritis sustained in long term Source: Reuters Medical News Date: June 27, 2003

•

Leflunomide comparable to sulfasalazine and methotrexate in rheumatoid arthritis Source: Reuters Medical News Date: June 18, 2003

•

FDA clears leflunomide for expanded rheumatoid arthritis indication Source: Reuters Medical News Date: June 17, 2003

•

FDA memos support leflunomide for treatment of arthritis Source: Reuters Medical News Date: March 04, 2003

•

Leflunomide/methotrexate combo may relieve hard-to-treat arthritis pain Source: Reuters Medical News Date: November 04, 2002

•

Etanercept superior to leflunomide for treating rheumatoid arthritis Source: Reuters Medical News Date: August 27, 2002

•

Public Citizen calls on FDA to ban Aventis' arthritis drug Arava Source: Reuters Industry Breifing Date: March 28, 2002

•

Dynamic MRI study differentiates leflunomide versus methotrexate for RA Source: Reuters Industry Breifing Date: March 12, 2002

•

Benefit of leflunomide for rheumatoid arthritis maintained at two years Source: Reuters Medical News Date: November 05, 2001

•

Long-term benefits of leflunomide confirmed in rheumatoid arthritis patients Source: Reuters Medical News Date: October 22, 2001

•

Methotrexate, leflunomide combination effective for rheumatoid arthritis Source: Reuters Industry Breifing Date: November 02, 2000

•

Leflunomide retards progression of rheumatoid arthritis Source: Reuters Medical News Date: April 12, 2000

Periodicals and News

•

Leflunomide as effective as methotrexate for rheumatoid arthritis Source: Reuters Medical News Date: November 30, 1999

•

Leflunomide equivalent to methotrexate for treatment of rheumatoid arthritis Source: Reuters Medical News Date: November 19, 1999

•

Leflunomide, methotrexate improve function, quality of life in rheumatoid arthritis Source: Reuters Medical News Date: October 19, 1999

•

Addition of leflunomide to methotrexate may be beneficial in rheumatoid arthritis Source: Reuters Medical News Date: July 21, 1999

•

Leflunomide efficacious against advanced solid tumors in early trial Source: Reuters Medical News Date: April 13, 1999

•

Leflunomide an alternative in rheumatoid arthritis Source: Reuters Medical News Date: November 11, 1998

•

FDA approves leflunomide for rheumatoid arthritis Source: Reuters Medical News Date: September 14, 1998

•

FDA panelists recommend approval of leflunomide for rheumatoid arthritis Source: Reuters Medical News Date: August 10, 1998

61

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

62

Leflunomide

Market Wire’s home page at http://www.marketwire.com/mw/home, type “leflunomide” (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 “leflunomide” (or synonyms). If you know the name of a company that is relevant to leflunomide, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “leflunomide” (or synonyms).

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

63

CHAPTER 7. 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 leflunomide. 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 leflunomide. 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

64

Leflunomide

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to leflunomide: Leflunomide •

Systemic - U.S. Brands: Arava http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203680.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. 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.

65

APPENDICES

67

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 Institute11: •

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/

11

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

68

Leflunomide

•

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

Physician Resources

69

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •

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

12

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). 13 See http://www.nlm.nih.gov/databases/databases.html.

70

Leflunomide

•

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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “leflunomide” (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 624 1 4 1 1 631

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “leflunomide” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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.

Physician Resources

71

Coffee Break: Tutorials for Biologists19 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.20 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.21 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/.

19 Adapted 20

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. 21 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.

73

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 leflunomide 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 leflunomide. 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 leflunomide. 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 “leflunomide”:

74

Leflunomide

Arthritis http://www.nlm.nih.gov/medlineplus/arthritis.html Juvenile Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/juvenilerheumatoidarthritis.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.html Rheumatoid Arthritis http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html Smallpox http://www.nlm.nih.gov/medlineplus/smallpox.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on leflunomide. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Leflunomide Source: Atlanta, GA: Arthritis Foundation. 1998. 6 p. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: Single copy free from local Arthritis Foundation chapter (call (800) 283-7800 for closest local chapter); bulk orders may be purchased from address above. Summary: This pamphlet uses a question and answer format to provide people who have arthritis with information on leflunomide. This disease modifying antirheumatic drug helps reduce the signs of inflammation and slow the rate of joint destruction in rheumatoid arthritis (RA). The drug is believed to work by affecting the function of certain immune cells involved in RA and the process of joint damage. Improvement from the drug may occur as soon as 4 weeks after beginning its use. Leflunomide, which is available only by prescription, comes in tablets of 10, 20, and 100 milligrams that are taken once per day. Side effects include skin rash, gastrointestinal symptoms, elevations of liver enzymes, and reversible hair loss. The drug should not be taken by people who have liver disease or known immune deficiency or women or men who are trying to conceive a child.

Patient Resources 75

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 leflunomide. 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

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

76

Leflunomide

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 “leflunomide” (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 “leflunomide”. 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 “leflunomide” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “leflunomide” (or a synonym) into the search box, and click “Submit Query.”

77

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.22

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

22

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

78

Leflunomide

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)23: •

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/

23

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

Finding Medical Libraries 79

•

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/

80

Leflunomide

•

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/

Finding Medical Libraries 81

•

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/

82

Leflunomide

•

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

83

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

85

LEFLUNOMIDE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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]

86

Leflunomide

Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]

Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] 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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of

Dictionary 87

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] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] 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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteritis: Inflammation of an artery. [NIH]

88

Leflunomide

Articular: Of or pertaining to a joint. [EU] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Aural: Pertaining to or perceived by the ear, as an aural stimulus. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] 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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving 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] Bladder: The organ that stores urine. [NIH]

Dictionary 89

Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual

90

Leflunomide

patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] 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 Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH]

Dictionary 91

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] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [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] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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

92

Leflunomide

that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [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] 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] Contusion: A bruise; an injury of a part without a break in the skin. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH]

Dictionary 93

Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] 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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [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] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention

94

Leflunomide

of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [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] Elasticity: Resistance and recovery from distortion of shape. [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] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous

Dictionary 95

phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [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]

Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] 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]

Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular

96

Leflunomide

proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluorescein Angiography: Visualization of a vascular system after intravenous injection of a fluorescein solution. The images may be photographed or televised. It is used especially in studying the retinal and uveal vasculature. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized

Dictionary 97

connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrointestinal: Refers to 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]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH]

98

Leflunomide

Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses, and woody plants. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herniated: Protrusion of a degenerated or fragmented intervertebral disc into the intervertebral foramen compressing the nerve root. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homotypic: Adhesion between neutrophils. [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] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used

Dictionary 99

of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [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] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several

100

Leflunomide

mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH]

Dictionary 101

Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

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] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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]

102

Leflunomide

Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Leflunomide: An anticancer drug that works by inhibiting a cancer cell growth factor. Also called SU101. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Levamisole: An antiparasitic drug that is also being studied in cancer therapy with fluorouracil. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Loading dose: A quantity higher than the average or maintenance dose, used at the initiation of therapy to rapidly establish a desired level of the drug [EU] 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] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and

Dictionary 103

diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lymphoproliferative Disorders: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [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] 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] 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]

104

Leflunomide

Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] 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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle

Dictionary 105

known as cardiac muscle. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a

106

Leflunomide

mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] 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] Ophthalmoscope: A lighted instrument used to examine the inside of the eye, including the retina and the optic nerve. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Otolaryngologist: A doctor who specializes in treating diseases of the ear, nose, and throat. Also called an ENT doctor. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH]

Dictionary 107

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more

108

Leflunomide

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] 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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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]

Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plaque Assay: Method for measuring viral infectivity and multiplication in cultured cells. Clear lysed areas or plaques develop as the viral particles are released from the infected cells during incubation. With some viruses, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain viral antigens which can be measured by immunofluorescence. [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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH]

Dictionary 109

Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH]

110

Leflunomide

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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] 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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH]

Dictionary 111

Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic

112

Leflunomide

nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] 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] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical

Dictionary 113

structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [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] 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] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] 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,

114

Leflunomide

maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Compression: Acute and chronic conditions characterized by external mechanical compression of the spinal cord due to extramedullary neoplasm; epidural abscess; spinal fractures; bony deformities of the vertebral bodies; and other conditions. Clinical manifestations vary with the anatomic site of the lesion and may include localized pain, weakness, sensory loss, incontinence, and impotence. [NIH] Spinal Fractures: Broken bones in the vertebral column. [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] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Steady state: Dynamic equilibrium. [EU] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU]

Dictionary 115

Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Symphysis: A secondary cartilaginous joint. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] 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] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU]

116

Leflunomide

Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombocytosis: Increased numbers of platelets in the peripheral blood. [EU] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual,

Dictionary 117

between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

118

Leflunomide

Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [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] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous

Dictionary 119

thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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]

121

INDEX A Abdomen, 85, 89, 102, 107, 114 Abdominal, 85, 101, 107 Abscess, 85, 114 Acetylcholine, 85, 105 Adjuvant, 85, 97 Adverse Effect, 85, 113 Affinity, 85, 102, 113 Agar, 85, 108 Airway, 36, 85 Albumin, 85, 106, 115 Algorithms, 57, 85, 88 Alimentary, 86, 101, 107 Alkylating Agents, 86, 117 Allergen, 86, 113 Allogeneic, 86, 98 Allograft, 28, 36, 49, 56, 86 Alopecia, 4, 9, 86, 92 Alpha Particles, 86, 111 Alternative medicine, 61, 86 Amino Acid Sequence, 86 Amino Acids, 86, 107, 109, 110 Analgesic, 46, 86 Analog, 6, 37, 86, 96 Anatomical, 86, 100, 112 Anesthesia, 85, 86 Angiogenesis, 6, 15, 86, 103 Animal model, 38, 50, 86 Antibacterial, 86, 114 Antibiotic, 86, 114 Antibodies, 5, 29, 50, 57, 86, 87, 102, 104, 108 Antibody, 9, 37, 85, 87, 91, 98, 99, 100, 104, 113 Anticoagulant, 8, 18, 87, 118 Antifungal, 87, 101 Antigen, 85, 87, 91, 97, 98, 99, 100, 113 Anti-inflammatory, 9, 12, 27, 50, 87, 90, 93, 97, 109 Anti-Inflammatory Agents, 87, 90 Antineoplastic, 86, 87, 92, 96, 99 Antiproliferative, 24, 25, 47, 52, 57, 87 Antipruritic, 87, 90 Antipyretic, 46, 87 Antiviral, 4, 87 Apoptosis, 21, 37, 87 Aqueous, 46, 87, 88, 93, 94 Arachidonic Acid, 87, 110

Arginine, 87, 105 Arterial, 37, 87, 99, 110, 115 Arteries, 87, 89, 92, 103, 104 Arterioles, 87, 89 Arteritis, 9, 87 Articular, 88, 106 Aspergillosis, 88, 101 Assay, 5, 36, 88 Atrial, 88, 119 Atrial Fibrillation, 88, 119 Aural, 53, 88 Autoimmune disease, 6, 7, 24, 37, 41, 48, 50, 88, 104 Autoimmunity, 19, 50, 88 Autoradiography, 5, 88 B Bacteria, 86, 87, 88, 94, 95, 103, 108, 114, 116, 117 Bacteriophage, 88, 108, 116 Base, 51, 88, 93, 101 Basement Membrane, 9, 17, 88, 95, 102 Bile, 88, 90, 96, 102, 114 Biliary, 88, 90 Binding Sites, 26, 88 Biochemical, 6, 12, 16, 26, 28, 88, 106 Biosynthesis, 10, 21, 23, 31, 47, 50, 51, 52, 87, 88 Biotechnology, 7, 8, 61, 69, 88 Bladder, 88, 100, 104, 110, 117 Blastomycosis, 89, 101 Blood pressure, 89, 99, 104, 113 Blood vessel, 41, 86, 89, 94, 95, 97, 102, 103, 113, 114, 116, 117 Blot, 5, 89 Body Fluids, 89, 113 Bone Marrow, 25, 89, 93, 98, 99, 102, 104, 114 Bowel, 89, 93 Bowel Movement, 89, 93 Bradykinin, 89, 105 Branch, 81, 89, 102, 107, 114, 115, 116 C Calcium, 89, 91, 103, 113 Capsules, 7, 89, 94, 97 Carcinogenic, 86, 89, 100, 110, 114 Cardiac, 36, 88, 89, 95, 105, 114 Carpal Tunnel Syndrome, 48, 89 Case report, 89

122

Leflunomide

Case series, 20, 89 Celecoxib, 32, 90 Cell Aggregation, 30, 90 Cell Cycle, 7, 90 Cell Death, 87, 90, 97, 105 Cell Differentiation, 90, 113 Cell Division, 88, 90, 104, 108 Cell proliferation, 13, 22, 37, 51, 90, 101, 113 Central Nervous System, 85, 90, 97, 104, 106 Cervical, 48, 90, 103 Cervix, 90 Cholesterol, 88, 90, 114 Cholestyramine, 4, 90 Choroid, 90, 112, 117 Chromatin, 87, 90 Chromosomal, 90, 108 Chronic, 6, 14, 28, 48, 49, 89, 90, 94, 95, 100, 110, 114, 115 Chronic renal, 28, 90 CIS, 90, 99, 112 Clinical trial, 4, 6, 16, 22, 26, 30, 41, 42, 56, 69, 91, 93, 111 Cloning, 88, 91 Coagulation, 89, 91, 118 Cochlea, 91 Cochlear, 53, 91, 116, 118 Cochlear Diseases, 91, 116 Collagen, 88, 91, 96, 97, 103, 109 Colloidal, 85, 91, 94 Combination Therapy, 6, 15, 25, 26, 91 Complement, 91, 113 Computational Biology, 69, 92 Conception, 92, 109, 114 Connective Tissue, 89, 91, 92, 96, 97, 102, 103, 112, 115 Consciousness, 86, 92 Contraindications, ii, 92 Contusion, 48, 92 Coordination, 92, 104 Cornea, 92, 112, 117 Coronary, 50, 92, 103, 104 Coronary Arteriosclerosis, 50, 92 Coronary Thrombosis, 92, 103, 104 Corticosteroids, 49, 57, 92, 97, 109 Cortisone, 92, 93, 109 Craniocerebral Trauma, 92, 116 Cultured cells, 92, 108 Curative, 92, 115 Cutaneous, 37, 89, 92, 102 Cyclic, 92, 98, 105, 108, 110

Cyclophosphamide, 38, 41, 57, 92 Cyclosporine, 11, 36, 38, 41, 49, 50, 57, 93, 99 Cytokine, 8, 12, 14, 37, 93, 107 Cytomegalovirus, 4, 16, 27, 93 Cytoplasm, 87, 93, 98, 104 Cytosine, 51, 93 Cytotoxic, 5, 93, 100, 113 D Databases, Bibliographic, 69, 93 De novo, 10, 20, 93 Degenerative, 93, 98, 106 Deletion, 87, 93 Demyelinating Diseases, 48, 93 Depolarization, 93, 113 Dermatitis, 13, 93 Dexamethasone, 14, 93 Diagnostic procedure, 45, 62, 93 Dialyzer, 93, 98 Diarrhea, 4, 90, 93 Diastolic, 93, 99 Digestion, 86, 88, 89, 93, 102, 114 Digestive system, 43, 93 Direct, iii, 63, 93, 111 Disease Progression, 29, 94, 118 Dizziness, 94, 118 Dosage Forms, 47, 51, 52, 94 Drug Interactions, 64, 94 E Efficacy, 3, 5, 8, 11, 13, 27, 30, 53, 94 Elasticity, 92, 94 Electrolyte, 94, 114 Electrons, 88, 94, 101, 111 Electrophoresis, 5, 94 Emboli, 94, 119 Embolism, 94, 111, 119 Embolization, 94, 119 Embryo, 90, 94, 109, 114 Embryo Transfer, 94, 109 Emulsion, 88, 94, 96 Endothelium, 95, 105 Endothelium-derived, 95, 105 Endotoxin, 95, 117 End-stage renal, 90, 95 Enhancer, 5, 95 Environmental Health, 68, 70, 95 Enzyme, 50, 95, 98, 106, 108, 109, 110, 112, 113, 115, 116, 118 Epidermal, 17, 95 Epidermal Growth Factor, 17, 95 Epidermis, 95 Epidural, 95, 114

Index 123

Epinephrine, 95, 117 Epithelial, 95, 98, 102 Epithelial Cells, 95, 98, 102 Epithelium, 88, 95 Erythrocytes, 89, 95, 107, 111, 113 Esophagus, 93, 95, 114 Extensor, 95, 110 Extracellular, 92, 95, 96, 103, 113 Extracellular Matrix, 92, 95, 96, 103 Extracellular Matrix Proteins, 96, 103 Extravasation, 96, 98 Extremity, 96, 103, 112 F Family Planning, 69, 96 Fat, 87, 89, 94, 96, 102, 104, 112, 114, 115 Fatty acids, 85, 96, 110 Fertilization in Vitro, 96, 109 Fibrosis, 96, 112 Fixation, 96, 113 Fluorescein Angiography, 41, 96 Fluorouracil, 96, 102 Foramen, 96, 98, 107 G Gallbladder, 85, 88, 93, 96 Ganglia, 85, 96, 105, 107 Gas, 97, 99, 105 Gastric, 94, 95, 97 Gastrointestinal, 74, 89, 95, 97, 115 Gelatin, 7, 97, 115 Gene, 5, 7, 15, 55, 88, 97 Gene Expression, 5, 15, 97 Giant Cells, 97, 112 Gland, 92, 97, 102, 107, 110, 113, 114, 115, 116 Glioma, 6, 97 Glomerular, 9, 17, 97, 111 Glomeruli, 97 Glomerulonephritis, 17, 97 Glomerulus, 97 Glucocorticoid, 9, 93, 97, 109 Glucose, 97, 100, 101, 112 Glycoprotein, 97, 102, 117 Gonadal, 97, 114 Governing Board, 97, 109 Grade, 7, 97 Graft, 4, 7, 49, 56, 97, 98, 104 Graft Rejection, 56, 98 Graft-versus-host disease, 98, 104 Granulocytes, 98, 113, 119 Grasses, 98 Growth, 5, 86, 87, 90, 95, 98, 101, 102, 105, 106, 108, 109, 116, 117

Guanylate Cyclase, 98, 105 H Half-Life, 50, 98 Hematoma, 48, 98 Heme, 98, 106 Hemodialysis, 12, 93, 98 Hemorrhage, 92, 98, 114 Hepatitis, 14, 98 Hepatocytes, 98 Herbicides, 50, 98 Heredity, 97, 98 Herniated, 48, 98 Herpes, 16, 98 Herpes Zoster, 98 Homologous, 98, 113, 115 Homotypic, 22, 98 Hormone, 92, 95, 98, 100, 109, 112, 113, 116 Host, 5, 7, 49, 88, 98, 99, 118 Humoral, 98 Hybrid, 7, 99 Hybridoma, 37, 99 Hydrogen, 88, 96, 99, 104, 105, 110 Hydroxyurea, 9, 99 Hypersensitivity, 37, 86, 99, 112, 113 Hypertension, 18, 99, 101 I Id, 39, 75, 80, 82, 99 Idiopathic, 99, 112 Illusion, 99, 118 Immune function, 99 Immune response, 13, 48, 49, 85, 87, 88, 92, 98, 99, 100, 113, 115, 118 Immune system, 41, 55, 88, 99, 102, 103, 104, 119 Immunization, 99, 113 Immunofluorescence, 99, 108 Immunoglobulin, 38, 86, 99, 104 Immunologic, 99, 107 Immunomodulator, 12, 21, 22, 99 Immunophilins, 7, 99 Immunosuppressant, 31, 37, 86, 96, 99 Immunosuppressive Agents, 13, 49, 57, 99 Immunosuppressive therapy, 4, 49, 100 Impairment, 100, 103 Impotence, 100, 114 In vitro, 6, 8, 13, 16, 22, 37, 56, 90, 94, 100, 115, 116 In vivo, 4, 6, 8, 15, 16, 37, 56, 100, 115 Incontinence, 100, 114 Incubated, 5, 100 Incubation, 100, 108

124

Leflunomide

Indicative, 56, 100, 107, 117 Infarction, 100 Infection, 89, 93, 99, 100, 102, 105, 106, 112, 113, 119 Infiltration, 97, 100 Inflammation, 10, 13, 21, 22, 23, 24, 26, 36, 41, 48, 74, 85, 87, 93, 96, 98, 100, 103, 112, 115, 117 Initiation, 16, 33, 100, 102, 116 Innervation, 100, 103, 107, 112, 116 Insulator, 100, 104 Insulin, 7, 100, 101 Insulin-dependent diabetes mellitus, 100, 101 Interleukin-1, 14, 101 Interleukin-2, 101 Interleukins, 100, 101 Interstitial, 101, 111 Intervertebral, 98, 101 Intestines, 85, 97, 101 Intracellular, 30, 100, 101, 105, 110, 113 Intracranial Hypertension, 101, 116 Intramuscular, 47, 101, 107 Intraperitoneal, 47, 101 Intravenous, 47, 96, 101, 107 Intrinsic, 85, 88, 101 Invasive, 101, 103 Ions, 88, 90, 94, 99, 101 Isomerases, 99, 101 Itraconazole, 14, 101 J Joint, 18, 33, 41, 55, 74, 88, 101, 106, 115 K Kb, 68, 101 Keto, 46, 101 L Laminin, 88, 96, 102 Large Intestine, 93, 101, 102, 111 Latency, 5, 102 Lesion, 89, 102, 114, 117 Leukocytes, 89, 98, 101, 102, 104, 107, 117 Leukocytosis, 20, 102 Levamisole, 11, 102 Library Services, 80, 102 Ligament, 102, 110 Lipid, 100, 101, 102, 104 Lipophilic, 46, 102 Liver, 4, 28, 38, 49, 60, 74, 85, 87, 88, 92, 93, 95, 96, 98, 102, 109, 112 Loading dose, 3, 102 Localized, 85, 96, 98, 100, 102, 108, 114, 117

Lumbar, 102, 112, 116 Lupus, 10, 102, 115 Lymph, 90, 95, 102, 112, 115 Lymph node, 90, 102, 112 Lymphatic, 95, 100, 102, 103, 109, 114 Lymphatic system, 102, 114 Lymphocyte, 11, 12, 31, 36, 50, 56, 87, 102 Lymphoid, 87, 92, 103 Lymphoproliferative, 6, 37, 103 Lymphoproliferative Disorders, 6, 103 M Macrophage, 101, 103 Magnetic Resonance Imaging, 11, 33, 103 Matrix metalloproteinase, 23, 30, 103 Median Nerve, 89, 103 MEDLINE, 69, 103 Melanin, 103, 108, 117 Membrane, 90, 91, 93, 102, 103, 111, 113, 115, 118 Meningitis, 101, 103 Mental Disorders, 43, 103 Mesenchymal, 95, 103 Metabolite, 6, 8, 9, 12, 15, 16, 25, 28, 29, 30, 31, 36, 38, 46, 49, 50, 52, 103 Metastasis, 103 MI, 83, 103 Microbe, 103, 116 Microorganism, 103, 118 Microscopy, 5, 88, 104 Migration, 16, 104 Mitochondrial Swelling, 104, 105 Mitosis, 87, 104 Mobility, 5, 104 Modification, 12, 104, 111 Molecular, 4, 26, 36, 47, 56, 69, 71, 88, 92, 104, 117 Molecule, 7, 46, 47, 87, 88, 91, 95, 101, 104, 108, 111, 113, 116, 117 Monitor, 104, 106 Monoclonal, 5, 57, 104 Monoclonal antibodies, 5, 57, 104 Monocytes, 101, 102, 104 Mononuclear, 22, 26, 104, 117 Monotherapy, 33, 104 Multiple sclerosis, 48, 104 Mycophenolate mofetil, 26, 36, 38, 56, 104 Myelin, 93, 104, 113 Myeloma, 99, 104 Myocardial infarction, 92, 103, 104, 119 Myocardium, 103, 104 N Nausea, 94, 105, 117

Index 125

NCI, 1, 42, 67, 90, 105 Necrosis, 9, 48, 87, 100, 103, 104, 105, 112 Need, 3, 50, 55, 56, 76, 90, 103, 105 Neoplasia, 105 Neoplasm, 105, 114, 117 Neoplastic, 5, 105 Nerve, 48, 86, 98, 100, 103, 104, 105, 106, 107, 109, 112, 113, 114, 116, 117, 118 Nervous System, 48, 90, 105, 107 Neuronal, 48, 105 Neurons, 96, 105, 115, 118 Neuropathy, 27, 48, 105 Neutrons, 86, 105, 111 Neutrophil, 16, 105 Nitric Oxide, 9, 36, 105 Nitrogen, 17, 92, 96, 105 Nuclear, 5, 15, 94, 105 Nuclei, 86, 94, 103, 104, 105, 106, 110, 118 Nucleic acid, 93, 105, 106 Nucleus, 87, 90, 92, 93, 104, 105, 106, 110, 118 O Observational study, 10, 30, 106 Ocular, 47, 106 Ointments, 94, 106 Ophthalmoscope, 41, 106 Opportunistic Infections, 4, 106 Optic Nerve, 106, 112 Organ Culture, 106, 116 Organ Transplantation, 14, 49, 106 Osteoarthritis, 74, 106 Otolaryngologist, 53, 106 Ovalbumin, 37, 106 Oxygenase, 8, 106 P Palliative, 107, 115 Pancreas, 85, 93, 100, 107 Pancytopenia, 27, 29, 107 Parenteral, 46, 47, 107 Parotid, 107, 112 Particle, 52, 107, 116 Pathologic, 87, 92, 99, 107, 110 Pathologic Processes, 87, 107 Patient Education, 74, 78, 80, 83, 107 Pelvic, 107, 110 Pentoxifylline, 26, 37, 107 Peptide, 107, 109, 110 Pericardium, 107, 115 Peripheral blood, 22, 26, 107, 116 Peripheral Nervous System, 93, 107, 115 Peritoneal, 101, 107 Peritoneal Cavity, 101, 107

Peroneal Nerve, 107, 112 Pharmaceutical Preparations, 97, 107 Pharmaceutical Solutions, 94, 107 Pharmacokinetic, 15, 57, 108 Pharmacologic, 4, 48, 86, 98, 108, 116 Phenyl, 52, 108 Phenylalanine, 108, 117 Phosphodiesterase, 107, 108 Phospholipases, 108, 113 Phosphorus, 89, 108 Phosphorylation, 5, 6, 16, 108 Physical Examination, 41, 108 Physiologic, 88, 98, 108, 110, 111 Plants, 97, 98, 108, 112, 116 Plaque, 5, 108 Plaque Assay, 5, 108 Plasma, 12, 29, 85, 87, 97, 104, 108, 113, 118 Plasma cells, 87, 104, 108 Plasmid, 5, 108, 117 Platelet Activation, 108, 113 Platelet Aggregation, 105, 107, 109 Platelet-Derived Growth Factor, 6, 109 Platelets, 105, 107, 108, 109, 116 Plexus, 103, 109, 112 Polymerase, 109, 112 Polymorphic, 47, 109 Polypeptide, 86, 91, 95, 109 Postoperative, 49, 109 Postsynaptic, 109, 113 Potentiate, 8, 18, 109 Potentiation, 109, 113 Practice Guidelines, 70, 109 Preclinical, 6, 109 Precursor, 87, 92, 108, 109, 117 Prednisolone, 109 Prednisone, 42, 109 Pregnancy Outcome, 24, 109 Progesterone, 109, 114 Progression, 4, 32, 60, 86, 110 Progressive, 49, 90, 98, 105, 106, 108, 110, 111, 117 Promoter, 5, 110 Prophylaxis, 110, 118 Prostaglandin, 27, 30, 110 Prostaglandins A, 110 Prostate, 48, 110 Protease, 91, 110 Protein S, 88, 110 Proteins, 5, 7, 86, 87, 89, 90, 91, 96, 99, 101, 103, 104, 105, 107, 108, 110, 116, 117 Proteoglycans, 88, 96, 110

126

Leflunomide

Protons, 86, 99, 110, 111 Psoriasis, 32, 110 Public Policy, 69, 111 Publishing, 7, 111 Pulmonary, 89, 111, 115, 119 Pulmonary Embolism, 111, 119 Q Quality of Life, 10, 14, 20, 61, 111 R Race, 104, 111 Radiation, 5, 88, 111, 119 Radioactive, 88, 98, 99, 104, 106, 111 Randomized, 11, 14, 16, 26, 28, 32, 33, 94, 111 Randomized Controlled Trials, 32, 111 Reactivation, 5, 111 Receptor, 5, 7, 14, 17, 25, 87, 111, 113 Rectum, 89, 93, 97, 100, 102, 110, 111, 115 Red blood cells, 95, 106, 111, 112 Refer, 1, 91, 94, 96, 98, 105, 111, 118 Refraction, 111, 114 Refractory, 33, 111 Regimen, 17, 94, 111 Renal failure, 9, 111 Reproduction Techniques, 109, 111 Restoration, 111, 119 Retina, 41, 90, 106, 111, 112, 117, 118 Retinal, 96, 106, 112 Reverse Transcriptase Inhibitors, 16, 112 Rheology, 107, 112 Rheumatism, 9, 10, 11, 14, 16, 17, 19, 21, 24, 26, 27, 28, 30, 32, 33, 112 Ribonucleoside Diphosphate Reductase, 99, 112 S Saline, 46, 112 Salivary, 5, 93, 112, 115 Salivary glands, 5, 93, 112 Saponins, 112, 114 Sarcoidosis, 29, 112 Sciatic Nerve, 48, 107, 112, 116 Sclera, 90, 112, 117 Sclerosis, 48, 104, 112 Screening, 42, 91, 113 Secretion, 95, 101, 113 Semen, 110, 113 Sensitization, 36, 38, 113 Sensory loss, 113, 114 Shock, 113, 117 Side effect, 41, 60, 63, 74, 85, 92, 113, 116 Signal Transduction, 5, 25, 113 Skeleton, 101, 110, 113

Smallpox, 74, 113 Smooth muscle, 37, 113, 115 Social Environment, 111, 113 Sodium, 41, 56, 113 Soft tissue, 89, 113, 114 Solid tumor, 6, 61, 86, 114 Specialist, 75, 114 Species, 49, 86, 95, 99, 104, 106, 111, 114, 115, 117, 118, 119 Spectrum, 47, 114 Spinal cord, 48, 90, 95, 103, 105, 107, 112, 114 Spinal Cord Compression, 48, 114 Spinal Fractures, 114 Spleen, 5, 93, 99, 102, 112, 114 Spontaneous Abortion, 109, 114 Steady state, 3, 114 Sterility, 92, 114 Steroid, 7, 41, 92, 112, 114 Stillbirth, 109, 114 Stimulus, 88, 100, 102, 114, 116 Stomach, 85, 93, 95, 97, 98, 101, 105, 107, 114 Stress, 57, 105, 112, 114 Stroke, 43, 68, 114 Subacute, 6, 100, 114 Subcutaneous, 47, 107, 115 Submaxillary, 95, 115 Subspecies, 114, 115 Substance P, 103, 113, 115 Substrate, 8, 101, 115 Suppositories, 97, 115 Suppression, 8, 29, 38, 115 Surfactant, 46, 115 Symphysis, 110, 115 Synaptic, 113, 115 Synergistic, 6, 115 Synovial, 9, 22, 26, 37, 55, 115 Synovial Fluid, 22, 115 Synovial Membrane, 115 Systemic, 10, 19, 64, 89, 95, 100, 101, 109, 112, 115, 119 Systemic lupus erythematosus, 10, 19, 115 Systolic, 99, 115 T Tacrolimus, 26, 38, 99, 115 Teratogen, 26, 30, 115 Therapeutics, 18, 22, 27, 31, 64, 115 Thermal, 47, 105, 115 Threshold, 99, 116 Thrombocytosis, 20, 116 Thrombosis, 110, 114, 116

Index 127

Thyroid, 116, 117 Tibial Nerve, 112, 116 Tin, 89, 116 Tinnitus, 53, 116, 118 Tissue Culture, 9, 116 Topical, 47, 116 Toxic, iv, 86, 98, 105, 116 Toxicity, 6, 25, 53, 94, 116 Toxicology, 70, 116 Toxins, 87, 100, 104, 116 Transcriptase, 112, 116 Transcription Factors, 5, 116 Transduction, 5, 113, 116 Transfection, 5, 88, 116 Trauma, 48, 105, 117 Treatment Failure, 31, 117 Tumor Necrosis Factor, 48, 117 Tumour, 9, 117 Tyrosine, 6, 16, 17, 50, 117 U Ulcer, 117 Ulceration, 24, 117 Unconscious, 99, 117 Uracil, 51, 117 Uremia, 111, 117 Urethra, 110, 117 Urine, 88, 95, 100, 117 Uterus, 90, 109, 117 Uvea, 117 Uveitis, 41, 117 V Vaccines, 117, 118 Vascular, 6, 14, 90, 95, 96, 100, 105, 117

Vascular endothelial growth factor, 6, 117 Vasculitis, 20, 33, 117 Vasodilators, 105, 117 Vector, 116, 117 Vein, 42, 101, 106, 107, 117, 118 Venous, 110, 118 Venous Thrombosis, 118, 119 Venules, 89, 118 Vertebrae, 101, 114, 118 Vertebral, 114, 118 Vertigo, 53, 118 Vesicular, 98, 113, 118 Vestibular, 53, 118 Vestibule, 91, 118 Vestibulocochlear Nerve, 116, 118 Vestibulocochlear Nerve Diseases, 116, 118 Veterinary Medicine, 69, 118 Viral, 5, 50, 97, 108, 116, 118 Viral Load, 5, 118 Virulence, 116, 118 Virus, 16, 88, 95, 97, 108, 113, 116, 118 Vitreous Body, 112, 118 Vitro, 118 Vivo, 6, 118 W Warfarin, 8, 18, 118 White blood cell, 87, 100, 102, 103, 104, 105, 108, 119 Wound Healing, 103, 119 X Xenograft, 49, 86, 119 X-ray, 47, 106, 119

128

Leflunomide

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

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Body Dysmorphic Disorder: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Dermabrasion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Septra: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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

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

Hip Pain: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

Marburg Virus: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

Recommend Documents