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

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

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Zocor: 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: 0-597-84251-5 1. Zocor-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Zocor. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ZOCOR....................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Zocor ............................................................................................. 4 E-Journals: PubMed Central ......................................................................................................... 6 The National Library of Medicine: PubMed .................................................................................. 6 CHAPTER 2. NUTRITION AND ZOCOR ............................................................................................. 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Zocor............................................................................................ 23 Federal Resources on Nutrition ................................................................................................... 24 Additional Web Resources ........................................................................................................... 25 CHAPTER 3. ALTERNATIVE MEDICINE AND ZOCOR ...................................................................... 27 Overview...................................................................................................................................... 27 National Center for Complementary and Alternative Medicine.................................................. 27 Additional Web Resources ........................................................................................................... 34 General References ....................................................................................................................... 36 CHAPTER 4. PATENTS ON ZOCOR ................................................................................................... 37 Overview...................................................................................................................................... 37 Patents on Zocor .......................................................................................................................... 37 Patent Applications on Zocor ...................................................................................................... 41 Keeping Current .......................................................................................................................... 45 CHAPTER 5. BOOKS ON ZOCOR ....................................................................................................... 47 Overview...................................................................................................................................... 47 Book Summaries: Online Booksellers........................................................................................... 47 Chapters on Zocor........................................................................................................................ 47 CHAPTER 6. PERIODICALS AND NEWS ON ZOCOR ......................................................................... 49 Overview...................................................................................................................................... 49 News Services and Press Releases................................................................................................ 49 Academic Periodicals covering Zocor .......................................................................................... 52 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 53 Overview...................................................................................................................................... 53 U.S. Pharmacopeia....................................................................................................................... 53 Commercial Databases ................................................................................................................. 54 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 57 Overview...................................................................................................................................... 57 NIH Guidelines............................................................................................................................ 57 NIH Databases............................................................................................................................. 59 Other Commercial Databases....................................................................................................... 62 APPENDIX B. PATIENT RESOURCES ................................................................................................. 63 Overview...................................................................................................................................... 63 Patient Guideline Sources............................................................................................................ 63 Finding Associations.................................................................................................................... 65 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 67 Overview...................................................................................................................................... 67 Preparation................................................................................................................................... 67 Finding a Local Medical Library.................................................................................................. 67 Medical Libraries in the U.S. and Canada ................................................................................... 67 ONLINE GLOSSARIES.................................................................................................................. 73 Online Dictionary Directories ..................................................................................................... 73

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ZOCOR DICTIONARY .................................................................................................................. 75 INDEX .............................................................................................................................................. 107

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Zocor is indexed in search engines, such as www.google.com or others, a nonsystematic 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 Zocor, 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 Zocor, 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 Zocor. 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 Zocor, 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 Zocor. The Editors

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

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

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

Treatment of Hypercholesterolemia and Combined Hyperlipidemia with Simvastatin and Gemfibrozil in Patients with NIDDM: A Multicenter Comparison Study Source: Diabetes Care. 21(4): 477-481. April 1998. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a double-blind, double-dummy study that investigated the lipid-lowering efficacy of simvastatin and gemfibrozil in Finnish patients who had type 2 diabetes and combined hyperlipidemia (CHL) or isolated hypercholesterolemia (IHC). Patients with primary dyslipidemia and type 2 diabetes treated with oral hypoglycemic agents and insulin, alone or in combination, were recruited from 10 Finnish centers participating in the study. After a 4-week placebo run-in period, they

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were randomly assigned to simvastatin or gemfibrozil. The 47 patients in the simvastatin group received 10 milligrams (mg) once a night for 8 weeks, 20 mg for the next 8 weeks, and 40 mg for the third 8-week period. The 49 patients in the gemfibrozil group received 600 mg twice a day throughout the 24 weeks. The lipid-lowering efficacy of both drugs was compared in all patients, as well as separately in patients with CHL and IHC. Results show that simvastatin reduced low density lipoprotein (LDL) and total cholesterol and the LDL-to-high density lipoprotein (HDL) cholesterol ratio more effectively in all patients, whereas gemfibrozil was more effective in elevating HDL cholesterol and decreasing triglyceride levels. The effects differed according to lipid phenotype at baseline. Simvastatin decreased LDL cholesterol levels by 30 to 40 percent in both phenotypes. Gemfibrozil caused a 15 percent reduction in LDL cholesterol in IHC but no change in CHL patients. Simvastatin produced 15 to 30 percent reductions in triglyceride levels in CHL but no change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL and in IHC patients, with 12 to 18 percent increases in HDL cholesterol in these groups. The article concludes that simvastatin is useful both in CHL and IHC patients, whereas gemfibrozil can be used in patients with high triglyceride and low or normal LDL cholesterol levels. 1 appendix. 2 figures. 3 tables. 26 references. (AA-M).

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

Project Title: EFFECTS OF DIET & MEDICATION IN PATIENTS WITH CEREBROTENDINOUS XANTHOMATOSIS Principal Investigator & Institution: Connor, William E.; Professor of Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001 Summary: Participants in this research study have an inherited condition that results in an elevated level of cholestanol (a break-down product of cholesterol) in the blood and tissues and a very reduced amount of a bile acid called chenodeoxycholic in the bile. The purpose of the study is to: 1) determine if feeding a diet that contains no cholestanol and

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

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no cholesterol will lower the amount of cholestanol in the blood 2) determine if taking simvastatin (Zocor), a drug that lowers the level of cholesterol in the blood and taking chenodeoxycholic acid will lower the level of cholestanol in the blood and reduce the size of the patient's xanthoma and make them feel better, 3) determine if and how much cholesterol and cholestanol are removed from the Achilles tendon after two years on medication and 4) use cells from a skin biopsy to study the genetics of CTX (cerebrotendinous xanthomatosis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS HYPERLIPIDEMIA

OF

SIMVASTATIN

ON

POSTPRANDIAL

Principal Investigator & Institution: Illingworth, D Roger.; Associate Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001 Summary: This research will study patients who have combined hyperlipidemia (increased blood levels of cholesterol and triglycerides). The study aims to look at the effects of simvastatin (Zocor) an approved drug for the treatment of hypercholesterolemia in patients who have elevated levels of blood cholesterol and concurrently moderately increased levels of blood triglycerides. Ten to twelve patients will be enrolled in the study at OHSU and it is planned to study a total of 50-60 patients at other participating centers in the United States. The purpose of this study is to assess how the body uses fats that may be eaten during the day and how the cholesterollowering drug simvastatin (Zocor) may reduce these fats in the blood after a fat-rich meal similar to a large milk-shake. We are also interested in assessing the effects of simvastatin on the body's production of cholesterol which will be measured by determination of the concentrations of a precursor of cholesterol which is excreted in the urine and how treatment with simvastatin affects the ability of white blood cells to take up cholesterol from the blood. We are also interested in measuring two enzymes known as lipoprotein lipase and hepatic lipase, which are responsible for the removal of the particles in the blood stream that contain cholesterol and other fats including new fat that enters the body after people have eaten a meal. We are trying to find out if treatment with simvastatin in addition to reducing concentrations of LDL cholesterol and triglyceride-rich lipoproteins can enhance clearance of fatty particles from the blood stream after ingestion of a fatty meal. These cholesterol-rich lipoproteins may increase the risk of developing atherosclerosis (the most common form of heart disease) and if simvastatin is shown to enhance their clearance this would be potentially of therapeutic benefit in reducing the risk of heart disease in patients with high blood levels of cholesterol and triglycerides. Until recently the maximal recommended dose of simvastatin for use in the treatment of hypercholesterolemia was 40 mg per day but a higher dose (80 mg per day) was approved in July 1998 by the FDA for the treatment of hypercholesterolemia and has been given to about 1,500 patients for a period of up to one year with a good safety profile. Participants in this study will receive three treatment periods, one of which will be a placebo, one will be simvastatin 20 mg per day and the third will be simvastatin 80 mg per day. Neither the participant nor the investigators will know which treatment is received although this information can be available if medically necessary. Participants will be asked to take two tablets of medications (a combination of simvastatin and placebo) once daily in the evening for a total period of 24 weeks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 “Zocor” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Zocor in the PubMed Central database: •

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors lovastatin and simvastatin inhibit in vitro development of Plasmodium falciparum and Babesia divergens in human erythrocytes. by Grellier P, Valentin A, Millerioux V, Schrevel J, Rigomier D.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188165

•

Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study. by Miettinen TA, Gylling H, Strandberg T, Sarna S.; 1998 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28514

•

Does simvastatin stimulate bone formation in vivo? by von Stechow D, Fish S, Yahalom D, Bab I, Chorev M, Muller R, Alexander JM.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156891

•

Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin. by Hsyu PH, Schultz-Smith MD, Lillibridge JH, Lewis RH, Kerr BM.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90851

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Simvastatin strongly reduces levels of Alzheimer's disease [beta]-amyloid peptides A[beta]42 and A[beta]40 in vitro and in vivo. by Fassbender K, Simons M, Bergmann C, Stroick M, Lutjohann D, Keller P, Runz H, Kuhl S, Bertsch T, von Bergmann K, Hennerici M, Beyreuther K, Hartmann T.; 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33303

•

Taking simvastatin in the morning compared with in the evening: randomised controlled trial. by Wallace A, Chinn D, Rubin G.; 2003 Oct 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=214096

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 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. 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

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

A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study. Author(s): Olsson AG, Eriksson M, Johnson O, Kjellstrom T, Lanke J, Larsen ML, Pedersen T, Tikkanen MJ, Wiklund O; 3T Study Investigators. Source: Clinical Therapeutics. 2003 January; 25(1): 119-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637115&dopt=Abstract

•

A novel anti-inflammatory role for simvastatin in inflammatory arthritis. Author(s): Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R, Campbell C, Gracie JA, Liew FY, McInnes IB. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 February 1; 170(3): 1524-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538717&dopt=Abstract

•

A randomized crossover study to evaluate LDL-cholesterol lowering effect of a generic product of simvastatin (Unison Company) compared to simvastatin (Zocor) in hypercholesterolemic subjects. Author(s): Assawawitoontip S, Wiwanitkit V. Source: J Med Assoc Thai. 2002 June; 85 Suppl 1: S118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188401&dopt=Abstract

•

Acute generalized exanthematous pustulosis induced by simvastatin. Author(s): Oskay T, Kutluay L. Source: Clinical and Experimental Dermatology. 2003 September; 28(5): 558-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950356&dopt=Abstract

•

Association between short-term simvastatin therapy before coronary artery bypass grafting and postoperative myocardial blood flow as assessed by positron emission tomography. Author(s): Dotani MI, Morise AP, Haque R, Jain AC, Gupta N, Gibson CM. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714156&dopt=Abstract

journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins, Creactive protein and in vivo oxidized LDL. Author(s): van den Akker JM, Bredie SJ, Diepenveen SH, van Tits LJ, Stalenhoef AF, van Leusen R. Source: Journal of Nephrology. 2003 March-April; 16(2): 238-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768071&dopt=Abstract

•

Atrial fibrillation induced by simvastatin treatment in a 61-year-old man. Author(s): Akahane T, Mizushige K, Nishio H, Fukui H, Kuriyama S. Source: Heart and Vessels. 2003 July; 18(3): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955433&dopt=Abstract

•

Beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival. Author(s): Conraads V. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2104; Author Reply 2104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798591&dopt=Abstract

•

By the way, doctor. My doctor recently prescribed Zocor to treat my high cholesterol. She plans to test my liver for possible side effects, which makes me nervous. Is this a dangerous drug? What are its side effects? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2000 June; 7(10): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10810072&dopt=Abstract

•

Chronic actinic dermatitis secondary to simvastatin. Author(s): Holme SA, Pearse AD, Anstey AV. Source: Photodermatology, Photoimmunology & Photomedicine. 2002 December; 18(6): 313-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535029&dopt=Abstract

•

Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin. Author(s): Hsu WC, Chen WH, Chang MT, Chiu HC. Source: Clinical Neuropharmacology. 2002 September-October; 25(5): 266-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410059&dopt=Abstract

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Comparative beneficial effects of simvastatin and pravastatin on cardiac allograft rejection and survival. Author(s): Mehra MR, Uber PA, Vivekananthan K, Solis S, Scott RL, Park MH, Milani RV, Lavie CJ. Source: Journal of the American College of Cardiology. 2002 November 6; 40(9): 1609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427413&dopt=Abstract

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•

Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidemia. Author(s): Milionis HJ, Papakostas J, Kakafika A, Chasiotis G, Seferiadis K, Elisaf MS. Source: Journal of Clinical Pharmacology. 2003 August; 43(8): 825-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953339&dopt=Abstract

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Comparative effects of diet and simvastatin on markers of thrombogenicity in patients with coronary artery disease. Author(s): Koh KK, Son JW, Ahn JY, Kim DS, Han SH, Ahn TH, Choi IS, Park GS, Shin EK. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1231-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745107&dopt=Abstract

•

Comparative effects of simvastatin and atorvastatin in hypercholesterolemic patients with characteristics of metabolic syndrome. Author(s): Hunninghake DB, Ballantyne CM, Maccubbin DL, Shah AK, Gumbiner B, Mitchel YB. Source: Clinical Therapeutics. 2003 June; 25(6): 1670-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860491&dopt=Abstract

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Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, doubleblind study. Author(s): Wu CC, Sy R, Tanphaichitr V, Hin AT, Suyono S, Lee YT. Source: J Formos Med Assoc. 2002 July; 101(7): 478-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353340&dopt=Abstract

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Comparison of effectiveness and safety of simvastatin in patients <75 versus > or =75 years of age with coronary, cerebral, or peripheral arterial disease. Author(s): Robinson JG, Conroy C, Wickemeyer WJ. Source: The American Journal of Cardiology. 2002 November 1; 90(9): 994-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398969&dopt=Abstract

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Comparison of in vitro hepatic models for the prediction of metabolic interaction between simvastatin and naringenin. Author(s): Le Goff N, Koffel JC, Vandenschrieck S, Jung L, Ubeaud G. Source: Eur J Drug Metab Pharmacokinet. 2002 October-December; 27(4): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587952&dopt=Abstract

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Comparison of the effects of atorvastatin versus simvastatin on subclinical atherosclerosis in primary preventionas determined by electronbeam tomography. Author(s): Hecht HS, Harman SM. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 42-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505569&dopt=Abstract

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Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Author(s): Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW; STELLAR Study Group. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 152-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860216&dopt=Abstract

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Comparison of the frequency of adverse events in patients treated with atorvastatin or simvastatin. Author(s): Abourjaily HM, Alsheikh-Ali AA, Karas RH. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 999-1002, A7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686348&dopt=Abstract

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Determination of Simvastatin in human plasma by liquid chromatography-mass spectrometry. Author(s): Yang H, Feng Y, Luan Y. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 March 5; 785(2): 369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554151&dopt=Abstract

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Differential effect of simvastatin on activation of Rac(1) vs. activation of the heat shock protein 27-mediated pathway upon oxidative stress, in human smooth muscle cells. Author(s): Negre-Aminou P, van Leeuwen RE, van Thiel GC, van den IJssel P, de Jong WW, Quinlan RA, Cohen LH. Source: Biochemical Pharmacology. 2002 November 15; 64(10): 1483-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417261&dopt=Abstract

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Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial. Author(s): Hyyppa MT, Kronholm E, Virtanen A, Leino A, Jula A. Source: Psychoneuroendocrinology. 2003 February; 28(2): 181-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510011&dopt=Abstract

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Effect of atorvastatin (80 mg) and simvastatin (40 mg) on plasma fibrinogen levels and on carotid intima media thickness in patients with familial hypercholesterolemia. Author(s): Trip MD, van Wissen S, Smilde TJ, Hutten BA, Stalenhoef AF, Kastelein JJ. Source: The American Journal of Cardiology. 2003 March 1; 91(5): 604-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615272&dopt=Abstract

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Effect of morning versus evening intake of simvastatin on the serum cholesterol level in patients with coronary artery disease. Author(s): Lund TM, Torsvik H, Falch D, Christophersen B, Skardal R, Gullestad L. Source: The American Journal of Cardiology. 2002 October 1; 90(7): 784-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356401&dopt=Abstract

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Effect of simvastatin on trioleylglycerol hydrolysis and transacylation with cholesterol in serum of outpatients with coronary heart disease. Author(s): Piorunska-Stolzmann M, Piorunska-Mikolajczak A, Mikolajczyk Z. Source: Drugs Exp Clin Res. 2003; 29(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866362&dopt=Abstract

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Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study. Author(s): Montagnani A, Gonnelli S, Cepollaro C, Pacini S, Campagna MS, Franci MB, Lucani B, Gennari C. Source: Bone. 2003 April; 32(4): 427-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689687&dopt=Abstract

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Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Author(s): Aronow WS, Nayak D, Woodworth S, Ahn C. Source: The American Journal of Cardiology. 2003 September 15; 92(6): 711-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972114&dopt=Abstract

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Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. Author(s): Vega GL, Ma PT, Cater NB, Filipchuk N, Meguro S, Garcia-Garcia AB, Grundy SM. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 956-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686335&dopt=Abstract

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Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments. Author(s): Desideri G, Croce G, Tucci M, Passacquale G, Broccoletti S, Valeri L, Santucci A, Ferri C. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 November; 88(11): 5341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602771&dopt=Abstract

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Effects of fenofibrate and simvastatin on plasma sICAM-1 and MCP-1 concentrations in patients with hyperlipoproteinemia. Author(s): Kowalski J, Okopien B, Madej A, Zielinski M, Belowski D, Kalina Z, Herman ZS. Source: Int J Clin Pharmacol Ther. 2003 June; 41(6): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816176&dopt=Abstract

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Effects of long term cholesterol lowering on coronary atherosclerosis in patient risk factor subgroups: the Simvastatin/enalapril Coronary Atherosclerosis Trial (SCAT). Author(s): Burton JR, Teo KK, Buller CE, Plante S, Catellier D, Tymchak W, Taylor D, Dzavik V, Montague TJ; SCAT investigators. Source: The Canadian Journal of Cardiology. 2003 April; 19(5): 487-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717482&dopt=Abstract

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Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. Author(s): Zhi J, Moore R, Kanitra L, Mulligan TE. Source: Journal of Clinical Pharmacology. 2003 April; 43(4): 428-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723464&dopt=Abstract

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Effects of simvastatin and L-arginine on vasodilation, nitric oxide metabolites and endogenous NOS inhibitors in hypercholesterolemic subjects. Author(s): Pereira EC, Bertolami MC, Faludi AA, Salem M, Bersch D, Abdalla DS. Source: Free Radical Research. 2003 May; 37(5): 529-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797474&dopt=Abstract

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Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients. Author(s): Bays HE, Stein EA, Shah AK, Maccubbin DL, Mitchel YB, Mercuri M. Source: The American Journal of Cardiology. 2002 November 1; 90(9): 942-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398959&dopt=Abstract

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Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Author(s): Mondillo S, Ballo P, Barbati R, Guerrini F, Ammaturo T, Agricola E, Pastore M, Borrello F, Belcastro M, Picchi A, Nami R. Source: The American Journal of Medicine. 2003 April 1; 114(5): 359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714124&dopt=Abstract

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Effects of simvastatin, an HMG-CoA reductase inhibitor, in patients with hypertriglyceridemia. Author(s): Isaacsohn J, Hunninghake D, Schrott H, Dujovne CA, Knopp R, Weiss SR, Bays H, Crouse JR 3rd, Davidson MH, Keilson LM, McKenney J, Korenman SG, Dobs AS, Stein E, Krauss RM, Maccubbin D, Cho M, Plotkin DJ, Mitchel YB. Source: Clin Cardiol. 2003 January; 26(1): 18-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12539808&dopt=Abstract

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Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial. Author(s): Brown WV, Bays HE, Hassman DR, McKenney J, Chitra R, Hutchinson H, Miller E; Rosuvastatin Study Group. Source: American Heart Journal. 2002 December; 144(6): 1036-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486428&dopt=Abstract

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Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized, double-blind, placebo-controlled trial with simvastatin. Author(s): de Jongh S, Ose L, Szamosi T, Gagne C, Lambert M, Scott R, Perron P, Dobbelaere D, Saborio M, Tuohy MB, Stepanavage M, Sapre A, Gumbiner B, Mercuri M, van Trotsenburg AS, Bakker HD, Kastelein JJ; Simvastatin in Children Study Group. Source: Circulation. 2002 October 22; 106(17): 2231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390953&dopt=Abstract

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Efficacy of simvastatin and ezetimibe in treating hypercholesterolemia. Author(s): Davidson MH. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 398-9; Author Reply 399. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875794&dopt=Abstract

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Enhanced interleukin-1beta in hypercholesterolemia: effects of simvastatin and lowdose aspirin. Author(s): Ferroni P, Martini F, Cardarello CM, Gazzaniga PP, Davi G, Basili S. Source: Circulation. 2003 October 7; 108(14): 1673-5. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504184&dopt=Abstract

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Enhanced sensitivity of G1 arrested human cancer cells suggests a novel therapeutic strategy using a combination of simvastatin and TRAIL. Author(s): Jin Z, Dicker DT, El-Deiry WS. Source: Cell Cycle (Georgetown, Tex.). 2002 January; 1(1): 82-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429913&dopt=Abstract

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Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. Author(s): Davidson MH, McGarry T, Bettis R, Melani L, Lipka LJ, LeBeaut AP, Suresh R, Sun S, Veltri EP. Source: Journal of the American College of Cardiology. 2002 December 18; 40(12): 212534. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505224&dopt=Abstract

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Flutamide-induced hepatotoxicity with possible potentiation by simvastatin. Author(s): Ashar U, Desai D, Bhaduri A. Source: J Assoc Physicians India. 2003 January; 51: 75-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693464&dopt=Abstract

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Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipidlowering goals. Author(s): Shepherd J, Hunninghake DB, Barter P, McKenney JM, Hutchinson HG. Source: The American Journal of Cardiology. 2003 March 6; 91(5A): 11C-17C; Discussion 17C-19C. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646338&dopt=Abstract

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Hemostatic effects of atorvastatin versus simvastatin. Author(s): Kadikoylu G, Yukselen V, Yavasoglu I, Bolaman Z. Source: The Annals of Pharmacotherapy. 2003 April; 37(4): 478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659599&dopt=Abstract

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High-dose simvastatin and rhabdomyolysis. Author(s): Wratchford P, Ponte CD. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 April 1; 60(7): 698-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701554&dopt=Abstract

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How effective is simvastatin 10 mg? Author(s): Young J. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 April; 53(489): 326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879839&dopt=Abstract

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I take Zocor for high cholesterol. My doctor checks my lipid levels every six months and they have been pretty good for a few years now. But he also checks my liverfunction tests, because liver damage is one of the side effects of this drug. How worried should I be about this problem, and is checking my liver tests every six months often enough? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 1998 September; 9(1): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9734250&dopt=Abstract

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In the past 12 to 18 months, my level of anxiety has increased significantly. I have been on atenolol and simvastatin (Zocor) for the past couple of years. Is there anything in these drugs that could cause this anxiety? Author(s): Lee TH. Source: Harvard Heart Letter : from Harvard Medical School. 1998 October; 9(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9780877&dopt=Abstract

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Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study. Author(s): Crea F, Monaco C, Lanza GA, Maggi E, Ginnetti F, Cianflone D, Niccoli G, Cook T, Bellomo G, Kjekshus J. Source: Clin Cardiol. 2002 October; 25(10): 461-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375804&dopt=Abstract

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Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Author(s): Dingemanse J, Schaarschmidt D, van Giersbergen PL. Source: Clinical Pharmacokinetics. 2003; 42(3): 293-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603176&dopt=Abstract

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Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia and coronary heart disease: secondary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT). Author(s): Mabuchi H, Kita T, Matsuzaki M, Matsuzawa Y, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H; J-LIT Study Group. Japan Lipid Intervention Trial. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 December; 66(12): 1096-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499612&dopt=Abstract

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Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia. Author(s): Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H; J-LIT Study Group. Japan Lipid Intervention Trial. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 December; 66(12): 1087-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499611&dopt=Abstract

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Lipid and apolipoprotein ratios: association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin, and simvastatin. Author(s): Rader DJ, Davidson MH, Caplan RJ, Pears JS. Source: The American Journal of Cardiology. 2003 March 6; 91(5A): 20C-23C; Discussion 23C-24C. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646340&dopt=Abstract

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Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years' follow-up by high-resolution noninvasive magnetic resonance imaging. Author(s): Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, Weinberger J, Wentzel J, Mizsei G, Mercuri M, Badimon JJ. Source: Circulation. 2002 December 3; 106(23): 2884-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460866&dopt=Abstract

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Lipid-lowering efficacy and safety of varying doses of Simvastatin in patients with early stage acute coronary syndromes: one-year follow-up study. Author(s): Zou Y, Hu D, Yang X, Xu Z, Cui L, Liu X, Wei Y, Gao M. Source: Chinese Medical Journal. 2003 June; 116(6): 853-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877794&dopt=Abstract

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Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2isoprostane formation in hypercholesterolemic subjects: no further effect of vitamin E. Author(s): De Caterina R, Cipollone F, Filardo FP, Zimarino M, Bernini W, Lazzerini G, Bucciarelli T, Falco A, Marchesani P, Muraro R, Mezzetti A, Ciabattoni G. Source: Circulation. 2002 November 12; 106(20): 2543-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427649&dopt=Abstract

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Merck-sponsored simvastatin (Zocor) compliance program for patients using WalMart Pharmacy: of benefit to whom? Author(s): Hirsch RL. Source: Jama : the Journal of the American Medical Association. 1998 June 17; 279(23): 1875-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9634257&dopt=Abstract

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Migration, proliferation, and invasion of human glioma cells following treatment with simvastatin. Author(s): Gliemroth J, Zulewski H, Arnold H, Terzis AJ. Source: Neurosurgical Review. 2003 May; 26(2): 117-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962298&dopt=Abstract

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MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Author(s): Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. Source: Lancet. 2003 June 14; 361(9374): 2005-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814710&dopt=Abstract

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On call. I'm a 62-year-old man in good health. I take Zocor for my cholesterol as well as a baby aspirin and several vitamins every day. My problem may seem silly, but it's really a nuisance: uncontrollable yawning. Do you have any idea why I yawn so much or what I can do about it? Author(s): Simon HB. Source: Harvard Men's Health Watch. 2002 April; 6(9): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959534&dopt=Abstract

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Rapid spectrophotometric method for quantitative determination of simvastatin and fluvastatin in human serum and pharmaceutical formulations. Author(s): Erk N. Source: Pharmazie. 2002 December; 57(12): 817-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561243&dopt=Abstract

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Recently, I heard on a TV show that anticholesterol drugs can cause hair loss. I've been taking Zocor for about 18 months now, and in the past 6 months I've noticed hair loss from the top and sides of my head. Is this common? Will my hair regrow once I stop taking the drug? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 1998 January; 5(5): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9600043&dopt=Abstract

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Regression of carotid and femoral artery intima-media thickness in familial hypercholesterolemia: treatment with simvastatin. Author(s): Nolting PR, de Groot E, Zwinderman AH, Buirma RJ, Trip MD, Kastelein JJ. Source: Archives of Internal Medicine. 2003 August 11-25; 163(15): 1837-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912721&dopt=Abstract

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Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. Author(s): Pappu AS, Bacon SP, Illingworth DR. Source: The Journal of Laboratory and Clinical Medicine. 2003 April; 141(4): 250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677170&dopt=Abstract

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Response to “The efficacy of simvastatin is not influenced by CYP2D6 polymorphism” by Geisel et al. Author(s): Mulder AB, van den Bergh FA, Vermes I. Source: Clinical Pharmacology and Therapeutics. 2003 May; 73(5): 475. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732847&dopt=Abstract

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Rhabdomyolysis associated with simvastatin-nefazodone therapy. Author(s): Skrabal MZ, Stading JA, Monaghan MS. Source: Southern Medical Journal. 2003 October; 96(10): 1034-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570351&dopt=Abstract

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Rhabdomyolysis from cytochrome p-450 interaction of ketoconazole and simvastatin in prostate cancer. Author(s): Itakura H, Vaughn D, Haller DG, O'Dwyer PJ. Source: The Journal of Urology. 2003 February; 169(2): 613. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544321&dopt=Abstract

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Rhabdomyolysis secondary to interaction of fusidic acid and simvastatin. Author(s): Yuen SL, McGarity B. Source: The Medical Journal of Australia. 2003 August 4; 179(3): 172. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885276&dopt=Abstract

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Simvastatin and markers of endothelial function in patients undergoing continuous ambulatory peritoneal dialysis. Author(s): Malyszko J, Malyszko JS, Hryszko T, Brzosko S, Mysliwiec M. Source: Int J Tissue React. 2002; 24(3): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635864&dopt=Abstract

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Simvastatin and pravastatin equally improve flow-mediated dilation in males with hypercholesterolemia. Author(s): Sebestjen M, Boh M, Keber I. Source: Wiener Klinische Wochenschrift. 2002 December 30; 114(23-24): 999-1003. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635468&dopt=Abstract

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Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass. Author(s): Chello M, Mastroroberto P, Patti G, D'Ambrosio A, Morichetti MC, Di Sciascio G, Covino E. Source: Heart (British Cardiac Society). 2003 May; 89(5): 538-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695460&dopt=Abstract

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Simvastatin effect on NK cells activity in vivo: a double-blind randomized, placebocontrolled study. Author(s): Santos AF, Keitel E, Bittar AE, Neumann J, Fonseca N, Sporleder H, Canabarro R, Kroth L, Saitovitch D, Garcia VD. Source: Transplantation Proceedings. 2002 November; 34(7): 2874-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431639&dopt=Abstract

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Simvastatin increases fibrinolytic activity in human peritoneal mesothelial cells independent of cholesterol lowering. Author(s): Haslinger B, Goedde MF, Toet KH, Kooistra T. Source: Kidney International. 2002 November; 62(5): 1611-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371961&dopt=Abstract

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Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Author(s): Contreras JL, Smyth CA, Bilbao G, Young CJ, Thompson JA, Eckhoff DE. Source: Transplantation. 2002 October 27; 74(8): 1063-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438947&dopt=Abstract

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Simvastatin induces apoptosis of B-CLL cells by activation of mitochondrial caspase 9. Author(s): Chapman-Shimshoni D, Yuklea M, Radnay J, Shapiro H, Lishner M. Source: Experimental Hematology. 2003 September; 31(9): 779-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962723&dopt=Abstract

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Simvastatin inhibits interleukin-6 release in human monocytes stimulated by Creactive protein and lipopolysaccharide. Author(s): Li JJ, Chen XJ. Source: Coronary Artery Disease. 2003 June; 14(4): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826933&dopt=Abstract

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Simvastatin initiated early after heart transplantation: 8-year prospective experience. Author(s): Wenke K, Meiser B, Thiery J, Nagel D, von Scheidt W, Krobot K, Steinbeck G, Seidel D, Reichart B. Source: Circulation. 2003 January 7; 107(1): 93-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515749&dopt=Abstract

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Simvastatin reduces plasma concentration of high-sensitivity C-reactive protein in type 2 diabetic patients with hyperlipidemia. Author(s): Lee IT, Sheu WH, Lin SY, Lee WJ, Song YM, Liu HC. Source: Journal of Diabetes and Its Complications. 2002 November-December; 16(6): 382-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477621&dopt=Abstract

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Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients. Author(s): Rezaie-Majd A, Prager GW, Bucek RA, Schernthaner GH, Maca T, Kress HG, Valent P, Binder BR, Minar E, Baghestanian M. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 March 1; 23(3): 397403. Epub 2003 January 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615677&dopt=Abstract

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Simvastatin treatment in the SLO syndrome: a safe approach? Author(s): Starck L, Lovgren-Sandblom A, Bjorkhem I. Source: American Journal of Medical Genetics. 2002 November 22; 113(2): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407710&dopt=Abstract

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Simvastatin, transdermal patch, and oral estrogen-progestogen preparation in earlypostmenopausal hypercholesterolemic women: a randomized, placebo-controlled clinical trial. Author(s): Vigna GB, Donega P, Zanca R, Barban A, Passaro A, Pansini F, Bonaccorsi G, Mollica G, Fellin R. Source: Metabolism: Clinical and Experimental. 2002 November; 51(11): 1463-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404199&dopt=Abstract

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Simvastatin. Author(s): LeBlanc K, Brophy MT. Source: Annals of Internal Medicine. 2003 June 17; 138(12): E1014. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809481&dopt=Abstract

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Simvastatin-associated rhabdomyolysis demonstrated on bone scan. Author(s): Rhodes CA, Balon HR. Source: Clinical Nuclear Medicine. 2002 November; 27(11): 793-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394127&dopt=Abstract

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Simvastatin-fluconazole causing rhabdomyolysis. Author(s): Shaukat A, Benekli M, Vladutiu GD, Slack JL, Wetzler M, Baer MR. Source: The Annals of Pharmacotherapy. 2003 July-August; 37(7-8): 1032-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841814&dopt=Abstract

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Simvastatin-induced lactic acidosis: a rare adverse reaction? Author(s): Goli AK, Goli SA, Byrd RP Jr, Roy TM. Source: Clinical Pharmacology and Therapeutics. 2002 October; 72(4): 461-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386648&dopt=Abstract

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Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death. Author(s): Hare CB, Vu MP, Grunfeld C, Lampiris HW. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 November 15; 35(10): E111-2. Epub 2002 October 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410494&dopt=Abstract

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Skin lesions due to treatment with simvastatin (Zocor) Author(s): Feldmann R, Mainetti C, Saurat JH. Source: Dermatology (Basel, Switzerland). 1993; 186(4): 272. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8513195&dopt=Abstract

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Stress responses after treatment of hypercholesterolaemia with simvastatin. Author(s): Nugent AM, Neely D, Young I, McDowell I, O'Kane M, Bell N, Stanford CF, Nicholls DP. Source: British Journal of Clinical Pharmacology. 1993 November; 36(5): 474-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959299&dopt=Abstract

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Suppression of the functionally coupled cyclooxygenase-2/prostaglandin E synthase as a basis of simvastatin-dependent plaque stabilization in humans. Author(s): Cipollone F, Fazia M, Iezzi A, Zucchelli M, Pini B, De Cesare D, Ucchino S, Spigonardo F, Bajocchi G, Bei R, Muraro R, Artese L, Piattelli A, Chiarelli F, Cuccurullo F, Mezzetti A. Source: Circulation. 2003 March 25; 107(11): 1479-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654603&dopt=Abstract

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Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients. Author(s): Matsuzawa Y, Kita T, Mabuchi H, Matsuzaki M, Nakaya N, Oikawa S, Saito Y, Sasaki J, Shimamoto K, Itakura H; J-LIT Study Group. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 April; 67(4): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655157&dopt=Abstract

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Taking simvastatin in the morning compared with in the evening: randomised controlled trial. Author(s): Wallace A, Chinn D, Rubin G. Source: Bmj (Clinical Research Ed.). 2003 October 4; 327(7418): 788. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14525878&dopt=Abstract

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The effect of low-dose simvastatin in children with familial hypercholesterolaemia: a 1-year observation. Author(s): Dirisamer A, Hachemian N, Bucek RA, Wolf F, Reiter M, Widhalm K. Source: European Journal of Pediatrics. 2003 June; 162(6): 421-5. Epub 2003 March 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756561&dopt=Abstract

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The efficacy of simvastatin is not influenced by CYP2D6 polymorphism. Author(s): Geisel J, Kivisto KT, Griese EU, Eichelbaum M. Source: Clinical Pharmacology and Therapeutics. 2002 November; 72(5): 595-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426523&dopt=Abstract

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The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Author(s): Prueksaritanont T, Ma B, Yu N. Source: British Journal of Clinical Pharmacology. 2003 July; 56(1): 120-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848784&dopt=Abstract

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Treatment with simvastatin in patients with Alzheimer's disease lowers both alphaand beta-cleaved amyloid precursor protein. Author(s): Sjogren M, Gustafsson K, Syversen S, Olsson A, Edman A, Davidsson P, Wallin A, Blennow K. Source: Dementia and Geriatric Cognitive Disorders. 2003; 16(1): 25-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714796&dopt=Abstract

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Two cases of rhabdomyolysis associated with high-dose simvastatin. Author(s): Skrabal MZ, Stading JA, Cannella CA, Monaghan MS. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 March 15; 60(6): 578-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659062&dopt=Abstract

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Zocor, the postmarketing experience. Author(s): Smart AJ, Walters L, Marais AD, Schoeman HS, Curran L. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1992 December; 82(6): 397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1465687&dopt=Abstract

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

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

7

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

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

A randomized crossover study to evaluate LDL-cholesterol lowering effect of a generic product of simvastatin (Unison Company) compared to simvastatin (Zocor) in hypercholesterolemic subjects. Author(s): Out-Patient Department, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Source: Assawawitoontip, S Wiwanitkit, V J-Med-Assoc-Thai. 2002 June; 85 Suppl 1: S118-24 0125-2208

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Effects of long-term treatment with simvastatin on some hemostatic parameters in continuous ambulatory peritoneal dialysis patients. Author(s): Department of Nephrology and Internal Medicine, Medical School, PL-15-540 Bialystok, Zurawia 14, Poland. [email protected] Source: Malyszko, J Malyszko, J S Hryszko, T Mysliwiec, M Am-J-Nephrol. 2001 SepOctober; 21(5): 373-7 0250-8095

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On call. I'm a 62-year-old man in good health. I take Zocor for my cholesterol as well as a baby aspirin and several vitamins every day. My problem may seem silly, but it's really a nuisance: uncontrollable yawning. Do you have any idea why I yawn so much or what I can do about it? Source: Simon, Harvey B Harv-Mens-Health-Watch. 2002 April; 6(9): 8 1089-1102

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The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy. Author(s): Duke University Medical Center and Duke University Clinical Research Institute, Durham, NC 27710, USA. [email protected] Source: Blazing, M A De Lemos, J A Dyke, C K Califf, R M Bilheimer, D Braunwald, E Am-Heart-J. 2001 August; 142(2): 211-7 0002-8703

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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

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

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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

Nutrition

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to Zocor; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com

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Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com

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Atorvastatin Source: Healthnotes, Inc.; www.healthnotes.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Fluvastatin Source: Healthnotes, Inc.; www.healthnotes.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com HMG-COA Reductase Inhibitors (Statins) Source: Integrative Medicine Communications; www.drkoop.com Lovastatin Source: Healthnotes, Inc.; www.healthnotes.com Pravastatin Source: Healthnotes, Inc.; www.healthnotes.com Simvastatin Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND ZOCOR Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Zocor. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Zocor and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Zocor” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to Zocor: •

A prospective clinical trial comparing the treatment of idiopathic membranous nephropathy and nephrotic syndrome with simvastatin and diet, versus diet alone. Author(s): Rayner BL, Byrne MJ, van Zyl Smit R. Source: Clinical Nephrology. 1996 October; 46(4): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8905205&dopt=Abstract

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Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men. Author(s): Neunteufl T, Kostner K, Katzenschlager R, Zehetgruber M, Maurer G, Weidinger F. Source: Journal of the American College of Cardiology. 1998 September; 32(3): 711-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9741516&dopt=Abstract

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An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease

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and persisting hypertriglyceridaemia. Author(s): Durrington PN, Bhatnagar D, Mackness MI, Morgan J, Julier K, Khan MA, France M. Source: Heart (British Cardiac Society). 2001 May; 85(5): 544-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303007&dopt=Abstract •

Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Author(s): Cheung MC, Zhao XQ, Chait A, Albers JJ, Brown BG. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 August; 21(8): 1320-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11498460&dopt=Abstract

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Association between short-term simvastatin therapy before coronary artery bypass grafting and postoperative myocardial blood flow as assessed by positron emission tomography. Author(s): Dotani MI, Morise AP, Haque R, Jain AC, Gupta N, Gibson CM. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714156&dopt=Abstract

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Baseline intestinal absorption and synthesis of cholesterol regulate its response to hypolipidaemic treatments in coronary patients. Author(s): Gylling H, Miettinen TA. Source: Atherosclerosis. 2002 February; 160(2): 477-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849674&dopt=Abstract

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Beyond the cholesterol profile: monitoring therapeutic effectiveness of statin therapy. Author(s): Schwartz RG. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2001 July-August; 8(4): 528-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481576&dopt=Abstract

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Cerebrotendinous xanthomatosis in three siblings from a Chinese family. Author(s): Ko KF, Lee KW. Source: Singapore Med J. 2001 January; 42(1): 030-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11361235&dopt=Abstract

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Characterization of endothelial factors involved in the vasodilatory effect of simvastatin in aorta and small mesenteric artery of the rat. Author(s): Alvarez De Sotomayor M, Herrera MD, Marhuenda E, Andriantsitohaina R. Source: British Journal of Pharmacology. 2000 November; 131(6): 1179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11082126&dopt=Abstract

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Comparative toxicity of high doses of vastatins currently used by clinicians, in CD-1 male mice fed with a hypercholesterolemic diet. Author(s): Diaz-Zagoya JC, Asenjo-Barron JC, Cardenas-Vazquez R, Martinez F, JuarezOropeza MA. Source: Life Sciences. 1999; 65(9): 947-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465354&dopt=Abstract

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Comparison of in vitro hepatic models for the prediction of metabolic interaction between simvastatin and naringenin. Author(s): Le Goff N, Koffel JC, Vandenschrieck S, Jung L, Ubeaud G. Source: Eur J Drug Metab Pharmacokinet. 2002 October-December; 27(4): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587952&dopt=Abstract

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Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Author(s): Sugimoto K, Ohmori M, Tsuruoka S, Nishiki K, Kawaguchi A, Harada K, Arakawa M, Sakamoto K, Masada M, Miyamori I, Fujimura A. Source: Clinical Pharmacology and Therapeutics. 2001 December; 70(6): 518-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753267&dopt=Abstract

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Differential effects of fenofibrate or simvastatin treatment of rats on hepatic microsomal overt and latent diacylglycerol acyltransferase activities. Author(s): Waterman IJ, Zammit VA. Source: Diabetes. 2002 June; 51(6): 1708-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031956&dopt=Abstract

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Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial. Author(s): Hyyppa MT, Kronholm E, Virtanen A, Leino A, Jula A. Source: Psychoneuroendocrinology. 2003 February; 28(2): 181-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12510011&dopt=Abstract

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Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor on sterol absorption in hypercholesterolemic subjects. Author(s): Ntanios FY, Jones PJ, Frohlich JJ. Source: Metabolism: Clinical and Experimental. 1999 January; 48(1): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9920147&dopt=Abstract

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Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Author(s): Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S.

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Source: Circulation. 2001 April 17; 103(15): 1933-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306519&dopt=Abstract •

Effect of long-term cholesterol-lowering treatment with HMG-CoA reductase inhibitor (simvastatin) on myocardial perfusion evaluated by thallium-201 single photon emission computed tomography. Author(s): Hosokawa R, Nohara R, Linxue L, Tamaki S, Hashimoto T, Tanaka M, Miki S, Sasayama S. Source: Japanese Circulation Journal. 2000 March; 64(3): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732848&dopt=Abstract

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Effect of omega-3 fatty acids and simvastatin on hemostatic risk factors and postprandial hyperlipemia in patients with combined hyperlipemia. Author(s): Nordoy A, Bonaa KH, Sandset PM, Hansen JB, Nilsen H. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 January; 20(1): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634827&dopt=Abstract

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Effect of statin therapy on remnant lipoprotein cholesterol levels in patients with combined hyperlipidemia. Author(s): Stein DT, Devaraj S, Balis D, Adams-Huet B, Jialal I. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 December; 21(12): 2026-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742880&dopt=Abstract

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Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. Author(s): Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Ronnemaa T. Source: Jama : the Journal of the American Medical Association. 2002 February 6; 287(5): 598-605. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829698&dopt=Abstract

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Effects of MK-733, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on absorption and excretion of [3H]cholesterol in rabbits. Author(s): Ishida F, Sato A, Iizuka Y, Sawasaki Y, Aizawa A, Kamei T. Source: Biochimica Et Biophysica Acta. 1988 November 4; 963(1): 35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3179328&dopt=Abstract

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Effects of short-term treatment of hyperlipidemia on coronary vasodilator function and myocardial perfusion in regions having substantial impairment of baseline dilator reverse. Author(s): Huggins GS, Pasternak RC, Alpert NM, Fischman AJ, Gewirtz H.

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Source: Circulation. 1998 September 29; 98(13): 1291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751677&dopt=Abstract •

Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. Author(s): Nordoy A, Bonaa KH, Nilsen H, Berge RK, Hansen JB, Ingebretsen OC. Source: Journal of Internal Medicine. 1998 February; 243(2): 163-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566646&dopt=Abstract

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Effects of simvastatin on hepatic cholesterol metabolism, bile lithogenicity and bile acid hydrophobicity in patients with gallstones. Author(s): Smith JL, Roach PD, Wittenberg LN, Riottot M, Pillay SP, Nestel PJ, Nathanson LK. Source: Journal of Gastroenterology and Hepatology. 2000 August; 15(8): 871-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022827&dopt=Abstract

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Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients: why is someone still using the phase I diet for patients at risk for atherosclerosis? Author(s): Banks T. Source: The American Journal of Cardiology. 1999 March 1; 83(5): 818. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080453&dopt=Abstract

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Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors. Author(s): Bargossi AM, Grossi G, Fiorella PL, Gaddi A, Di Giulio R, Battino M. Source: Molecular Aspects of Medicine. 1994; 15 Suppl: S187-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7752830&dopt=Abstract

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Fish oil supplementation in patients with heterozygous familial hypercholesterolemia. Author(s): Balestrieri GP, Maffi V, Sleiman I, Spandrio S, Di Stefano O, Salvi A, Scalvini T. Source: Recenti Prog Med. 1996 March; 87(3): 102-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8650428&dopt=Abstract

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High dose of simvastatin normalizes postprandial remnant-like particle response in patients with heterozygous familial hypercholesterolemia. Author(s): Twickler TB, Dallinga-Thie GM, de Valk HW, Schreuder PC, Jansen H, Cabezas MC, Erkelens DW. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 November; 20(11): 2422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11073847&dopt=Abstract

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High-dose simvastin (80 mg/day) decreases plasma concentrations of total homocyst(e)ine in patients with hypercholesteromia. Author(s): Luftjohann D, Sigit JI, Locatelli S, von Bergmann K, Schmidt HH. Source: Atherosclerosis. 2001 March; 155(1): 265-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293393&dopt=Abstract

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Identifying patients at risk for coronary heart disease: implications from trials of lipid-lowering drug therapy. Author(s): Isles CG, Paterson JR. Source: Qjm : Monthly Journal of the Association of Physicians. 2000 September; 93(9): 567-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984551&dopt=Abstract

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Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis. Author(s): Baller D, Notohamiprodjo G, Gleichmann U, Holzinger J, Weise R, Lehmann J. Source: Circulation. 1999 June 8; 99(22): 2871-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10359730&dopt=Abstract

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In vitro inhibition of simvastatin metabolism in rat and human liver by naringenin. Author(s): Ubeaud G, Hagenbach J, Vandenschrieck S, Jung L, Koffel JC. Source: Life Sciences. 1999; 65(13): 1403-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10503959&dopt=Abstract

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Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy. Author(s): Blair SN, Capuzzi DM, Gottlieb SO, Nguyen T, Morgan JM, Cater NB. Source: The American Journal of Cardiology. 2000 July 1; 86(1): 46-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867091&dopt=Abstract

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Ineffective decrease of serum cholesterol by simvastatin in a subgroup of hypercholesterolemic coronary patients. Author(s): Miettinen TA, Gylling H. Source: Atherosclerosis. 2002 September; 164(1): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119203&dopt=Abstract

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Involvement of tyrosine phosphorylation in HMG-CoA reductase inhibitor-induced cell death in L6 myoblasts. Author(s): Mutoh T, Kumano T, Nakagawa H, Kuriyama M.

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Source: Febs Letters. 1999 February 5; 444(1): 85-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10037153&dopt=Abstract •

Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3. Author(s): Teiber JF, Draganov DI, La Du BN. Source: Biochemical Pharmacology. 2003 September 15; 66(6): 887-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963475&dopt=Abstract

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LDL cholesterol lowering by bile acid malabsorption during inhibited synthesis and absorption of cholesterol in hypercholesterolemic coronary subjects. Author(s): Gylling H, Miettinen TA. Source: Nutr Metab Cardiovasc Dis. 2002 February; 12(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125225&dopt=Abstract

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Long-term effect of simvastatin on the improvement of impaired myocardial flow reserve in patients with familial hypercholesterolemia without gender variance. Author(s): Yokoyama I, Yonekura K, Inoue Y, Ohtomo K, Nagai R. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2001 July-August; 8(4): 445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11481566&dopt=Abstract

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Making the most of cholesterol-lowering margarines. Author(s): Avery JK. Source: Cleve Clin J Med. 2001 March; 68(3): 194-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11263847&dopt=Abstract

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Meeting highlights. Highlights of the 48th scientific sessions of the American College of Cardiology. Author(s): Ferguson JJ. Source: Circulation. 1999 August 10; 100(6): 570-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441090&dopt=Abstract

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Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol. Author(s): Miettinen TA, Strandberg TE, Gylling H. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 May; 20(5): 1340-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10807752&dopt=Abstract

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PKC activity in rat C6 glioma cells: changes associated with cell cycle and simvastatin treatment. Author(s): Soma MR, Baetta R, Bergamaschi S, De Renzis MR, Davegna C, Battaini F, Fumagalli R, Govoni S.

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Source: Biochemical and Biophysical Research Communications. 1994 April 29; 200(2): 1143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8179595&dopt=Abstract •

Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts. Author(s): Di Napoli P, Antonio Taccardi A, Grilli A, Spina R, Felaco M, Barsotti A, De Caterina R. Source: Cardiovascular Research. 2001 August 1; 51(2): 283-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470468&dopt=Abstract

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Simvastatin stimulates VEGF release via p44/p42 MAP kinase in vascular smooth muscle cells. Author(s): Takenaka M, Hirade K, Tanabe K, Akamatsu S, Dohi S, Matsuno H, Kozawa O. Source: Biochemical and Biophysical Research Communications. 2003 January 31; 301(1): 198-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535662&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to Zocor; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Angkak Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Beni-koji Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Cholesterol-Lowering Drugs Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc.www.personalhealthzone.com Hong Qu Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Hung-chu Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Monascus Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com

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Red Koji Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Leaven Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Rice Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Alternative names: Angkak Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10054,00.html Zhitai Alternative names: Red Yeast Rice Source: Integrative Medicine Communications; www.drkoop.com Zue Zhi Kang Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON ZOCOR Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Zocor” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Zocor, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Zocor By performing a patent search focusing on Zocor, 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

8Adapted

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

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

Methyl analogs of simvastatin as novel HMG-CoA reductase inhibitors Inventor(s): Kumar; Saridi Madhava Dileep (Andhra Pradesh, IN), Kumar; Yatendra (Haryana, IN), Thaper; Rajesh Kumar (Hidersbad, IN) Assignee(s): Ranbaxy Laboratories Limited (New Delhi, IN) Patent Number: 6,541,511 Date filed: June 10, 2002 Excerpt(s): The present invention relates to a novel methyl analog of simvastatin, which has the ability to inhibit the synthesis of cholesterol. The compound of the present invention holds promise for the treatment and prophylaxis of hypercholesterolemia and of various cardiac disorders. The invention also relates to a process for making the novel compound. Hypercholesterolemia is a known primary risk factor for the progression of atherosclerosis. High serum cholesterol is regarded as a major risk factor for the development of ischaemic heart disease and there is, therefore, a need for drugs which have the effect of reducing the blood cholesterol levels. was preserved, thereby establishing it as a key structural feature responsible for its HMG-CoA reductase inhibitory activity. Soon afterwards, intense efforts were directed to the design and development of synthetic strategies for selectively modifying the side-chain ester and the lactone moieties of mevinolin. Web site: http://www.delphion.com/details?pn=US06541511__

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Process for manufacturing simvastatin and the novel intermediates Inventor(s): Acharya; Poornaprajna (Bangalore, IN), Mathew; Joy (Bangalore, IN), Sambasivam; Ganesh (Bangalore, IN), Sridharan; Madhavan (Bangalore, IN) Assignee(s): Biocon India Limited (Bangalore District, IN) Patent Number: 6,573,392 Date filed: May 10, 2002 Abstract: This invention describes the synthesis of simvastatin from lovastatin by converting the lovastatin to lova amide using a secondary amine and subsequent reaction with a metal amide base generated from n-butyl lithium and pyrrolidine and followed by treatment with methyl iodide to give desired C-methylated intermediate. This intermediate was further transformed to the final product, simvastatin. This method of production consumes lesser quantities of metal amide, gives fewer side reactions and a lowered overall cost of manufacture of simvastatin than other procedures reported. Excerpt(s): The naturally occurring compounds of formula I and their semi-synthetic analogs are very active antihypercholesterolemic agents that function by limiting the cholesterol biosynthesis by inhibiting the HMG-CoA reductase enzyme. Compounds of formula Ia, shown in page 9, include the natural fermentation products like mevinolin (disclosed in U.S. Pat No. 4,231,938 and also known as lovastatin), compactin (disclosed in U.S. Pat No. 3,983,240) and a variety of semi-synthetic and totally synthetic analogs thereof, all having the natural 2-methylbutyrate side chain. Compounds of formula IIa, shown in page 9, having a 2,2-dimethylbutyrate side chain (e.g., simvastatin) are known

Patents 39

to be more active inhibitors of HMG-CoA reductase than their 2-methylbutyate analogs and thus of greater utility in the treatment of artherosclerosis, hyperlipemia, familial hypercholesterolemia and similar disorders. Web site: http://www.delphion.com/details?pn=US06573392__ •

Process for manufacturing simvastatin from lovastatin or mevinolinic acid Inventor(s): Khanna; Jag Mohan (New Delhi, IN), Kumar; S. M. Dileep (New Delhi, IN), Kumar; Yatendra (Haryana, IN), Misra; Satyananda (New Delhi, IN), Thaper; Rajesh Kumar (Haryana, IN) Assignee(s): Ranbaxy Laboratories, Ltd. (New Delhi, IN) Patent Number: 5,763,646 Date filed: March 13, 1997 Abstract: A process for preparing simvastatin from lovastatin or mevinolinic acid in salt form comprises treating either starting material with cyclopropyl or butyl amine, the pyranone ring thereby being opened when lovastatin is the starting material, adding a methyl group to the 2-methylbutyrate side chain, and thereafter closing the open pyranone ring to produce simvastatin. The process is performed without protecting and deprotecting the two hydroxy groups of the open pyranone ring. In a preferred embodiment, the starting material is treated with cyclopropyl amine which produces simvastatin via the novel intermediate lovastatin cyclopropyl amide. Excerpt(s): This patent application is related to a patent application entitled "KEY INTERMEDIATES IN THE MANUFACTURE OF SIMVASTATIN" assigned Ser. No. 08/816,574, and filed on Mar. 13, 1997. Compounds of structure I include the natural fermentation products mevinolin (structure Ia where R.dbd.CH.sub.3, disclosed in U.S. Pat. No. 4,231,938, and also known as lovastatin), compactin (structure Ib where R.dbd.H, disclosed in U.S. Pat. No. 3,983,140), and a variety of semi-synthetic and totally synthetic analogs thereof, all having the natural 2-methylbutyrate side chain. The recent introduction into the market of simvastatin (IIa), a more potent HMG-CoA reductase inhibitor than lovastatin (Ia), has provided a need for a high yielding process which is more economically efficient and environmentally sound than those disclosed in the prior art. Web site: http://www.delphion.com/details?pn=US05763646__

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Process for producing simvastatin and analogs thereof Inventor(s): Kubela; Rudolf (Stouffville, CA), Radhakrishnan; Jayaramaiyer (Winnipeg, CA) Assignee(s): Apotex, Inc. (Ontario, CA) Patent Number: 5,393,893 Date filed: November 8, 1993 Abstract: A process is disclosed for the preparation of simvastatin and its analogs through a novel intermediate (III), which enables a selective.alpha. carbon alkylation of the C-8 acyl side chain.

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Excerpt(s): Certain mevalonate derivatives are known to inhibit the activity of HMGCoA reductase, the rate-controlling enzyme in the biosynthetic pathway for cholesterol. They are mevastatin (also called compactin), lovastatin (also known as mevinolin or monacolin K) and analogs of these compounds such as pravastatin and simvastatin. Mevastatin and lovastatin are natural fermentation products which possess a 2methylbutyrate side chain in the 8-position of their hexahydronaphthalene ring system. It was proven by others that products having a 2,2-dimethylbutyrate side chain in this position are more active inhibitors of HMG-CoA reductase than analogs with a 2methylbutyrate side chain. There are basically three known routes to introduce the additional.alpha.-methyl group to the 8-acyl side chain of lovastatin or mevastatin and their analogs. Web site: http://www.delphion.com/details?pn=US05393893__ •

Process for the preparation of simvastatin and analogs thereof Inventor(s): Zlicar; Marco (Celje, SI) Assignee(s): Lek Pharmaceutical and Chemical Company d.d. (Ljubljana, SI) Patent Number: 6,384,238 Date filed: May 31, 2001 Abstract: Lovastatin, pravastatin, simvastatin, mevastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, and some are obtained by treating the fermentation products using the methods of chemical synthesis for example simvastatin. This invention relates to the novel method for the acylation of sterically hindered alcohols which is applicable in the process for the preparation of simvastatin and derivatives thereof. Excerpt(s): Lovastatin, pravastatin, simvastatin, mevastatin, atorvastatin, derivatives and analogs thereof are known as HMG-CoA reductase inhibitors and are used as antihypercholesterolemic agents. The majority of them are produced by fermentation using microorganisms of different species identified as species belonging to Aspergillus, Monascus, Nocardia, Amycolatopsis, Mucor or Penicillium genus, some are obtained by treating the fermentation products using the methods of chemical synthesis (simvastatin) or they are the products of total chemical synthesis. In the literature several processes for the preparation of simvastatin are known which are mainly based on one of the two following basic principles. A process of direct methylation of the 2-(S)methylbutyryloxy side chain of lovastatin is disclosed in U.S. Pat. No. 4,582,915. That process is based on direct methylation of the 2-(S)-methylbutyryloxy side chain of lovastatin using a methyl alkyl amide and a methyl halide in a single step. The described process has certain disadvantages: the low level of conversion in the Cmethylation step, low temperatures (-70 to -15.degree. C.) required for the reaction to be carried out and a number of undesired side reactions of methylation occurring at other sites of the molecule as well as using of butyl lithium which produces an explosive reaction with water and is highly pyrogen at higher concentrations. With minor modifications the yields in the methylation step may be improved, however, the total yields remain relatively low. U.S. Pat. No. 4,820,850 discloses a process for methylation of the 2-(S)-methylbutyrylox side chain of lovastatin using a single charge of amide base

Patents 41

and alkyl halide. The process disclosed therein involves six steps; despite the fact that the level of conversion is high in the methylation step, the process is not economical. Web site: http://www.delphion.com/details?pn=US06384238__ •

Process to simvastatin ester Inventor(s): Dabora; Rebecca L. (Andover, MA), Tewalt; Gregory L. (Shenandoah, VA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,159,104 Date filed: May 1, 1991 Abstract: A process is disclosed, for the formation of simvastatin, which comprises the sequential acylation of a diol lactone to form a bis acylated intermediate followed by selective deacylation and lactone ring closure to form simvastatin. Excerpt(s): Hypercholesterolemia is known to be one of the prime risk factors for atherosclerosis and coronary heart disease, the leading cause of death and disability in western countries. The bile acid sequestrants seem to be moderately effective as antihyperchloesterolemic agents but they must be consumed in large quantities, i.e., several grams at a time, and they are not very palatable. Simvastatin is now commercially available as ZOCOR.RTM. in some markets. The preparation of simvastatin was originally described in U.S. Pat. No. 4,444,784. The process involves deacylation of lovastatin followed by a subsequent acylation with the 2,2dimethylbutyryl moiety. Simvastatin has also been prepared by the alpha alkylation of the lovastatin ester moiety as described in U.S. Pat. Nos. 4,582,915 and 4,820,850. Web site: http://www.delphion.com/details?pn=US05159104__

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

Dihydroxy open-acid salt of simvastatin Inventor(s): Grabowski, Edward J. J.; (Westfield, NJ), Reider, Paul J.; (Westfield, NJ), Tillyer, Richard D.; (Cranford, NJ), Varsolona, Richard J.; (Scotch Plains, NJ), Vega, Jose M.; (Trappe, PA), Wenslow, Robert M.; (East Windsor, NJ), Xu, Feng; (Staten Island, NY) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030176501 Date filed: November 13, 2002 Abstract: The instant invention provides methods and pharmaceutical compositions for inhibiting HMG-CoA reductase, as well as for treating and/or reducing the risk for diseases and conditions affected by inhibition of HMG-CoA reductase, comprising orally administering a therapeutically effective amount of a crystalline hydrated form of

9

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

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the calcium salt of dihydroxy open acid simvastatin to a patient in need of such treatment. Methods for making the calcium salt of dihydroxy open acid simvastatin are also provided. Excerpt(s): This application is a continuation-in-part of attorney docket case no. 20357YPIB having U.S. Ser. No. ______ filed Sep. 6, 2000, which is a continuation-in-part of attorney docket case no. 20357YPIA having U.S. Ser. No. ______ filed Aug. 30, 2000, which is a continuation-in-part of PCT/US2000/02627, filed Feb. 2, 2000, which is a continuation-in-part of U.S. Ser. No. 09/264,745, filed Mar. 9, 1999, which is a nonprovisional application claiming priority to provisional application S No. 60/123,247, filed Mar. 8, 1999, all of which are herein incorporated by reference in their entirety. The instant invention relates to crystalline calcium salt of dihydroxy open acid simvastatin, and its use as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. It has been clear for several decades that elevated blood cholesterol is a major risk factor for coronary heart disease (CHD), and many studies have shown that the risk of CHD events can be reduced by lipid-lowering therapy. Prior to 1987, the lipidlowering armamentarium was limited essentially to a low saturated fat and cholesterol diet, the bile acid sequestrants (cholestyramine and colestipol), nicotinic acid (niacin), the fibrates and probucol. Unfortunately, all of these treatments have limited efficacy or tolerability, or both. With the introduction of lovastatin (MEVACOR.RTM.; see U.S. Pat. No. 4,231,938), the first inhibitor of HMG-CoA reductase to become available for prescription in 1987, for the first time physicians were able to obtain comparatively large reductions in plasma cholesterol with very few adverse effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Highly purified simvastatin compositions Inventor(s): Istvan, Melczer; (Debrecen, HU), Korodi, Ferenc; (Debrecen, HU), Leonov, David; (Rehovot, IL), Salyi, Szabolcs; (Debrecen, HU), Szabo, Csaba; (Debrecen, HU) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020115712 Date filed: July 26, 2001 Abstract: The present invention relates to a process to prepare semi synthetic statins, to intermediates formed during said process and to highly purified simvastatin produced by the process. Excerpt(s): This application claims the benefit of U.S. provisional applications No. 60/221,112, filed Jul. 27, 2000, incorporated herein by reference. Statin drugs are currently the most therapeutically effective drugs available for reducing the level of LDL in the blood stream of a patient at risk for cardiovascular disease. This class of drugs includes lovastatin, simvastatin, pravastatin, compactin, fluvastatin and atorvastatin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 43

•

Prevention of liver cancer by administration of simvastatin Inventor(s): Weinberg, Assa; (Los Angeles, CA) Correspondence: Dave B. Koo, ESQ.; Squire, Sanders & Dempsey L.L.P.; 801 S. Figueroa Street, 14th Floor; Los Angeles; CA; 90017-5554; US Patent Application Number: 20020151583 Date filed: April 11, 2001 Abstract: A method for preventing liver cancer is disclosed. In one embodiment, the method comprises administrating an effective amount of simvastatin to patients showing elevated alphafetoprotein levels. In another embodiment, the method comprises administrating simvastatin to patients upon detection of a liver condition, i.e viral Hepatitis B, Hepatitis C and liver cirrhosis. Excerpt(s): In spite of substantial advances in the understanding of the mechanism of oncogenesis (transformation of a normal cell into a malignant one), a method to prevent and reverse such oncogenic process has not been put into practice. Many environmental, dietary and genetic factors play a significant role in the formation of a malignant tumor, but no drug is known to prevent the formation of a malignant tumor. In many cases, patients affected with a malignant tumor are deemed to be terminal. Cancer of the liver or hepatocellular carcinoma is a particular case in point. It is an aggressive and rapidly spreading disease. Even with the combined use of the four classic treatment modalities, surgery, radiation, chemotherapy and immunotherapy--little has been changed to alter the grim prospect. The only methods capable of eradicating liver cancer at the present time are partial resection of the liver in the case where the malignancy is localized or complete extirpation of the malignant liver and a replacement by transplantation. In liver transplantation cases, the cost of the procedure is substantial, followed by a lifelong administration of anti-rejection drugs, and medical follow-up involving doctor visits, blood tests, and imaging studies. Patients with advanced liver diseases, and in particular, patients with viral hepatitis B and C are known to be at a high risk of developing liver cancer. In the United States, there are 70,000 new hepatitis B cases and more than 250,000 newly diagnosed hepatitis C cases each year. Around the world and especially in Southeast Asia and China, Hepatitis B and C are at epidemic proportion without a cure in sight. The case is particularly serious as the Hepatitis virus can be transmitted during delivery to the newborn baby. This was demonstrated in recent studies from Taiwan in which 40% of babies born to Hepatitis B or C carrier mothers were found to be positive for the same, a few days after delivery or a month later. In the same token hepatocellular carcinoma is at epidemic proportions in this region and represents a major public health issue for these countries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

PROCESS FOR PRODUCING SIMVASTATIN Inventor(s): HORNE, STEPHEN E; (BURLINGTON, CA), MURTHY, K. S. KESHAVA; (BRANTFORD, CA), WEERATUNGA, GAMINI; (BRANTFORD, CA), YOUNG, SHAWN; (BRANTFORD, CA) Correspondence: Ivor M Hughes; Suite 200; 175 Commerce Valley Drive West; Thornhill; L3t7p6; CA Patent Application Number: 20010053859 Date filed: November 21, 1996

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Abstract: A process for manufacturing Simvastatin is provided comprising reacting lovastatin with an organic boronic acid to produce a derivative of lovastatin with a hemiboronate group attached to the C-4 carbon of the pyranyl group, methylating the 2methylbutyryloxy group on the lovastatin derivative to form a 2,2-dimethylbutyryloxy group on the lovastatin derivative and thereafter removing the hemiboronate group to produce simvastatin. Excerpt(s): This invention relates to the preparation of SIMVASTATIN. This invention also relates to the purification of intermediates which may be used in the preparation of simvastatin. More broadly, this invention relates to processes for the alkylation at an.alpha.-carbon of an ester (containing one or two.alpha.-hydrogens) in a molecule which also contains a.beta.-hydroxylactone functional group with one or two.alpha.hydrogens. Mevastatin (also known as compactin) and lovastatin (also known as mevinolin) are naturally occuring HMG-CoA reductase inhibitors. These compounds have been used medicinally in the control of human serum cholesterol levels. Both compounds contain a (2S)-2-methylbutyryloxy substituent at the C-8 position of their hexahydronaphthalene nucleus and both produce medicinal analogues with increased potency towards HMG-CoA reductase when the aforementioned 2-methylbutyryloxy side chain is converted into a 2,2-dimethylbutyryloxy group. The analogue which is obtained from lovastatin by such a conversion is known as simvastatin. A method for the commercial scale production of simvastatin from lovastatin is the subject of the present invention. In the second procedure, the acetate of simvastatin is hydrolyzed using an enzymatic preparation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for producing simvastatin and/or its derivatives Inventor(s): Dalen, Frans Van; (Nuenen, NL), Lemmens, Jacobus Maria; (Mook, NL), Peters, Theororus Hendricus Antonius; (Arnhem, NL), Picha, Frantisek; (Brno, CZ), Van Helvoirt, Gertruda Antonetta Philomina; (Nijmegen, NL) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020035274 Date filed: June 18, 2001 Abstract: A process for the production of simvastatin and its analogues that is efficient, economical and convenient involves the use of hydroxyl protected intermediates of formula (III) or (VII). These intermediates allow for direct alkylation of the butyrate side chain followed by deprotection and reformation of the lactone ring. 1R.sup.1 is hydrogen or methyl; R.sup.2 represents a straight or branched chain alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, or an aralkyl group having I to 6 carbon atoms in the alkyl chain; R.sup.3 and R.sup.4 each independently represent an alkyl group, an ether group, a thioether group, an aryl group, an aralkyl group, an alkenyl group, a cyclic ether group, or a cyclic thioether group; and R.sup.5 and R.sup.6 each independently represent hydrogen, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, or an ether group. Excerpt(s): The present invention relates to a process for producing simvastatin and/or derivatives thereof as well as to a process for producing intermediates for said compounds, and to various intermediates themselves. Certain hexahydronaphthalene derivatives are known as potent inhibitors of the enzyme HMG-CoA reductase, the rate-

Patents 45

controlling enzyme in the biosynthetic pathway for formation of cholesterol in the human body. Well known examples of these compounds are mevastatin (U.S. Pat. No. 3,983,140), lovastatin (U.S. Pat. No. 4,231,938), pravastatin (U.S. Pat. No. 4,346,227) and simvastatin (U.S. Pat. No. 4,444,784). All of these compounds are important pharmaceuticals and are widely used in hyperchotesterolaemic treatments. One route to introduce an additional a-methyl group to the 8-acyl side chain of lovastatin (formula (B)) or its analogues is disclosed in U.S. Pat. No. 4,444,784. This process involves indirect methylation of the said side chain through several chemical steps: deesterification of the whole 2-methylbutyrate side chain, protection of the 4-hydroxy group in the pyranone ring by a tert-butylldimethylsilyl protective group, reesterification of the protected lactone with 2,2-dimethylbutyric acid, and deprotection of the hydroxy group of the pyranone ring. This procedure involves multiple chemical reactions with a low overall yield. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Simvastatin dosage forms Inventor(s): Dalen, Frans Van; (Nijmegen, NL), Lemmens, Jacobus M.; (Mook, NL) Correspondence: Fleshner & Kim, Llp; P.O. Box 221200; Chantilly; VA; 20153; US Patent Application Number: 20030153617 Date filed: December 17, 2002 Abstract: A pharmaceutical tablet comprising an effective amount of simvastatin provides several advantages including reliable or improved storage stability by having a pH within the range of 5.0 to 7.5, based on a 20 wt % aqueous slurry. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119(e) from provisional patent application Ser. No. 60/340,268, filed Dec. 18, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to pharmaceutical tablet compositions containing simvastatin and to methods of making and using the same. which is now known as simvastatin. Simvastatin is an effective 3hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The inhibition of HMG-CoA reductase causes a reduction in cholesterol production and hence the antihypercholesterolemic effect. Simvastatin is commercially sold in the U.S. and elsewhere under the brand name ZOCOR.TM. by Merck & Company, Inc. In general, the commercially available ZOCOR.TM. tablets contain simvastatin (5, 10, 20, 40, or 80 mg), anhydrous lactose, microcrystalline cellulose (carriers), pregellatinized maize starch (disintegrant), magnesium stearate (lubricant), butylated hydroxyanisol (BHA), citric acid monohydrate and ascorbic acid (antioxidants). The tablet is coated by a waterdispersible film-coat comprising hydroxypropyl cellulose, HPMC, talc and colorants. 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 Zocor, 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:

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

47

CHAPTER 5. BOOKS ON ZOCOR Overview This chapter provides bibliographic book references relating to Zocor. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Zocor 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: 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 “Zocor” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “Zocor” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Zocor” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Statin Adjunct Therapy - Zetia, Revenue Protection for Zocor? [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000AUH5W; http://www.amazon.com/exec/obidos/ASIN/B0000AUH5W;/icongroupinterna

Chapters on Zocor In order to find chapters that specifically relate to Zocor, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Zocor 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 “Zocor” (or synonyms) into the “For these words:” box.

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

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

Reuters Summit - Zetia-Zocor studies don't aim to play up safety Source: Reuters Industry Breifing Date: November 24, 2003

•

Schering-Plough, Merck seek US OK for Zetia/Zocor Source: Reuters Industry Breifing Date: November 18, 2003

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•

UK to cut price of generic simvastatin and omeprazole Source: Reuters Industry Breifing Date: October 15, 2003

•

India's Ranbaxy gets US FDA nod for generic Zocor Source: Reuters Industry Breifing Date: September 29, 2003

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Germany's Merck to sell US Merck's Zocor in UK Source: Reuters Industry Breifing Date: April 29, 2003

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Merck's Zocor label adds heart benefit data Source: Reuters Industry Breifing Date: April 17, 2003

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Cardiovascular benefit data added to Zocor label Source: Reuters Medical News Date: April 17, 2003

•

Simvastatin may slow multiple sclerosis progression Source: Reuters Industry Breifing Date: April 02, 2003

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Novartis arm to launch Zocor in Britain Source: Reuters Industry Breifing Date: March 20, 2003

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Generic Zocor will limit sales of Crestor -- analysts Source: Reuters Industry Breifing Date: March 17, 2003

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Merck's Zocor topples AstraZeneca's Losec as top-selling drug in Britain Source: Reuters Industry Breifing Date: April 29, 2002

•

Merck's Zocor gets six additional months of exclusivity Source: Reuters Industry Breifing Date: February 27, 2002

•

Simvastatin plus niacin reduces MI risk factors in patients with coronary disease Source: Reuters Medical News Date: November 28, 2001

•

Merck's Zocor cuts cardiovascular risk dramatically in major trial Source: Reuters Industry Breifing Date: November 13, 2001

•

Bentley to market generic versions of Merck's Zocor in Spain Source: Reuters Industry Breifing Date: November 05, 2001

•

UK bulletin recommends Merck's Zocor over other statins Source: Reuters Industry Breifing Date: March 27, 2001

•

Simvastatin recommended as first-line therapy for hyperlipidemia in UK Source: Reuters Medical News Date: March 27, 2001

Periodicals and News

•

Bristol-Myers' Pravachol, Merck's Zocor lower marker of inflammation Source: Reuters Industry Breifing Date: March 21, 2001

•

FDA approves new starting dose for Merck's Zocor for high LDL Source: Reuters Industry Breifing Date: May 02, 2000

•

Merck's simvastatin gets additional FDA indication Source: Reuters Medical News Date: August 10, 1999

•

FDA approves new dose range for Zocor Source: Reuters Medical News Date: July 14, 1998

•

FDA Approves Merck's Simvastatin To Reduce Risk Of Stroke, TIA Source: Reuters Medical News Date: April 03, 1998

•

Merck's Zocor Approved For Additional Indication Source: Reuters Medical News Date: November 07, 1997

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Zocor” (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.

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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 “Zocor” (or synonyms). If you know the name of a company that is relevant to Zocor, 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 “Zocor” (or synonyms).

Academic Periodicals covering Zocor Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Zocor. In addition to these sources, you can search for articles covering Zocor that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 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 Zocor. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with Zocor. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to Zocor: HMG-COA Reductase Inhibitors •

Systemic - U.S. Brands: Baycol; Lescol; Lipitor; Mevacor; Pravachol; Zocor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202284.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.

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APPENDICES

57

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

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

•

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

•

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

•

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

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

•

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

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

•

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

10

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

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•

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

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

•

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

•

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

•

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

•

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

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

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

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

•

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

•

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

•

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

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “Zocor” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “Zocor” (or synonyms) into the “For these words:” box. The following is a sample result: •

Treatment of Hypercholesterolemia and Combined Hyperlipidemia with Simvastatin and Gemfibrozil in Patients with NIDDM: A Multicenter Comparison Study Source: Diabetes Care. 21(4): 477-481. April 1998. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a double-blind, double-dummy study that investigated the lipid-lowering efficacy of simvastatin and gemfibrozil in Finnish patients who had type 2 diabetes and combined hyperlipidemia (CHL) or isolated hypercholesterolemia (IHC). Patients with primary dyslipidemia and type 2 diabetes treated with oral hypoglycemic agents and insulin, alone or in combination, were recruited from 10 Finnish centers participating in the study. After a 4-week placebo run-in period, they were randomly assigned to simvastatin or gemfibrozil. The 47 patients in the simvastatin group received 10 milligrams (mg) once a night for 8 weeks, 20 mg for the next 8 weeks, and 40 mg for the third 8-week period. The 49 patients in the gemfibrozil group received 600 mg twice a day throughout the 24 weeks. The lipid-lowering efficacy of both drugs was compared in all patients, as well as separately in patients with CHL and IHC. Results show that simvastatin reduced low density lipoprotein (LDL) and total cholesterol and the LDL-to-high density lipoprotein (HDL) cholesterol ratio more effectively in all patients, whereas gemfibrozil was more effective in elevating HDL cholesterol and decreasing triglyceride levels. The effects differed according to lipid phenotype at baseline. Simvastatin decreased LDL cholesterol levels by 30 to 40 percent in both phenotypes. Gemfibrozil caused a 15 percent reduction in LDL cholesterol in IHC but no change in CHL patients. Simvastatin produced 15 to 30 percent reductions in triglyceride levels in CHL but no change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL and in IHC patients, with 12 to 18 percent increases in HDL cholesterol in these groups. The article concludes that simvastatin is useful both in CHL and IHC patients, whereas gemfibrozil can be used in patients with high triglyceride and low or normal LDL cholesterol levels. 1 appendix. 2 figures. 3 tables. 26 references. (AA-M).

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The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Zocor” (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 2039 2 932 17 0 2990

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “Zocor” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI 13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 18 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

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

19

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Zocor 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 Zocor. 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 Zocor. 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 “Zocor”:

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•

Other guides Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Heart Transplantation http://www.nlm.nih.gov/medlineplus/hearttransplantation.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Zocor. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Zocor” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

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

•

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

•

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/

22

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

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

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

•

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

•

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

•

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

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ZOCOR 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] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of

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antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [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] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino 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] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH]

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Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] 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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antidepressant: A drug used to treat depression. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] 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] Arcus Senilis: A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera. [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] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the

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most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atrial: Pertaining to an atrium. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] 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] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bezafibrate: Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in

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the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood 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] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the

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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]

Breakdown: A physical, metal, or nervous collapse. [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] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are

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made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrotendinous Xanthomatosis: A primary fatty degeneration of the cornea occurring physiologically as an arcus senilis. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Choleretic: A choleretic agent. [EU] Cholestanol: A cholesterol derivative found in human feces, gallstones, eggs, and other biological matter. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] 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] 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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from

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the small intestines to the tissues. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Claudication: Limping or lameness. [EU] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy,

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spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conjugated: Acting or operating as if joined; simultaneous. [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] 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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial

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function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [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] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome P-450: Isozymes which are key components of the mixed-function oxidase system responsible for the biotransformation of many foreign compounds to mutagens and carcinogens. Most mammals have several distantly related phenobarbital-inducible gene subfamilies. EC 1.13.-. [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] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss

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of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] 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] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, 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] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]

Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH]

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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] 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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] 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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH]

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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] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [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]

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Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [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]

Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] 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] 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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] 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] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH]

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Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of

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water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypoglycemic Agents: Agents which lower the blood glucose level. [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] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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]

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Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Inotropic: Affecting the force or energy of muscular contractions. [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] 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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intestinal: Having to do with the intestines. [NIH] 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]

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Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] 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] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-low-

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density lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH]

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Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

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] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesothelial: It lines the peritonealla and pleural cavities. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] 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] 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,

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can be made up of many thousands of atoms. [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] 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] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action

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toward a goal he believes will satisfy the impulse. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] 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] 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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orlistat: A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that

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assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30 percent. It is known colloquially as a "fat blocker." Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence. Orlistat may not be suitable for people with bowel conditions such as irritable bowel syndrome or Crohn's disease. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pelvic: Pertaining to the pelvis. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the

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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] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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

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regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] 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] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection,

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as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [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] Progestogen: A term applied to any substance possessing progestational activity. [EU] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] 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 C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va

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and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] 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] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage

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the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [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] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] 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] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU]

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Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Soybean Oil: Oil from soybean or soybean plant. [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] Stabilization: The creation of a stable state. [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] 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] 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] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] 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]

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Supplementation: Adding nutrients to the diet. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Systemic: Affecting the entire body. [NIH] Talc: A native magnesium silicate. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] 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] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50

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to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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 Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [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] 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] White blood cell: A type of cell in the immune system that helps the body fight infection

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and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Xanthoma: A tumour composed of lipid-laden foam cells, which are histiocytes containing cytoplasmic lipid material. Called also xanthelasma. [EU] Xanthomatosis: A condition of morphologic change in which there is accumulation of lipids in the large foam cells of tissues. It is the cutaneous manifestation of lipidosis in which plasma fatty acids and lipoproteins are quantitatively changed. The xanthomatous eruptions have several different distinct morphologies dependent upon the specific form taken by the disease. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yawning: An involuntary deep inspiration with the mouth open, often accompanied by the act of stretching. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]

107

INDEX A Abdomen, 75, 79, 93, 97, 103 Abdominal, 75, 90, 92, 94, 97, 98 Acceptor, 75, 92, 97 Acetylcholine, 75, 96 Acidosis, 21, 75 Acyl, 39, 40, 45, 75 Acylation, 40, 41, 75 Adaptability, 75, 81 Adenocarcinoma, 75, 89 Adenosine, 75, 76, 98 Adipose Tissue, 75, 93 Adrenergic, 75, 78, 86, 100 Adverse Effect, 42, 75, 102 Aerobic, 75, 105 Affinity, 75, 92 Agar, 76, 99 Age of Onset, 76, 104 Algorithms, 76, 79 Alkaline, 75, 76, 80 Alkylation, 39, 41, 44, 76 Allograft, 8, 76 Allylamine, 76 Alpha Particles, 76, 101 Alternative medicine, 51, 76 Ambulatory Care, 76 Amine, 38, 39, 76 Amino Acids, 76, 99, 101, 102 Amiodarone, 12, 76 Ammonia, 76 Amyloid, 6, 22, 77 Anal, 77, 93, 97 Analog, 38, 77 Anatomical, 77, 78, 85, 90, 102 Aneurysm, 77, 105 Antianginal, 76, 77 Antiarrhythmic, 76, 77 Antidepressant, 77, 87 Antifungal, 77, 87, 92 Anti-inflammatory, 7, 77, 78 Anti-Inflammatory Agents, 77, 78 Antioxidant, 28, 77, 78, 97 Antipruritic, 77, 81 Antiviral, 77, 96 Anxiety, 15, 77, 100 Aorta, 28, 77, 80, 83, 90 Apolipoproteins, 77, 88, 92 Apoptosis, 19, 77, 80

Aqueous, 45, 77, 78, 84, 89 Arachidonic Acid, 77, 100 Arcus Senilis, 77, 81 Arginine, 12, 77, 96 Arterial, 9, 11, 76, 77, 81, 90, 101 Arteries, 77, 78, 79, 83, 84, 90, 93, 94, 95 Arteriosclerosis, 20, 28, 30, 31, 33, 77, 90, 95 Ascorbic Acid, 45, 78 Aspirin, 13, 17, 24, 78 Atenolol, 15, 78 Atrial, 8, 76, 78 Atrium, 78, 80 Autoimmune disease, 78, 95 Axillary, 78, 79 Axillary Artery, 78, 79 B Bacteria, 75, 78, 87, 94, 103, 105 Bacteriophage, 78, 99 Base, 38, 40, 78, 84, 92 Beta-pleated, 77, 78 Bezafibrate, 12, 78 Bile, 4, 31, 33, 41, 42, 78, 79, 81, 87, 93, 103, 104 Bile Acids, 78, 103, 104 Bile Acids and Salts, 78 Bile Ducts, 79, 87 Biliary, 79, 81 Bilirubin, 79, 87 Biopsy, 5, 79 Biosynthesis, 38, 77, 79, 93, 102, 103 Biotechnology, 6, 51, 59, 79 Biotransformation, 79, 84 Bladder, 79, 90, 95, 100, 105 Blood Coagulation, 79, 80 Blood Glucose, 79, 89, 90, 91 Blood pressure, 79, 80, 90, 97 Blood vessel, 79, 80, 81, 86, 92, 94, 97, 103, 104, 105 Bone Marrow, 79, 90, 95 Bone scan, 20, 79 Bowel, 77, 79, 92, 96, 98 Brachial, 27, 79 Brachial Artery, 27, 79 Bradykinin, 79, 96 Branch, 71, 80, 96, 97, 101, 103, 104 Breakdown, 80, 85, 87, 103

108 Zocor

C Calcium, 42, 80, 82, 86, 95 Candidiasis, 80, 87 Capillary, 80, 93 Capsules, 80, 85, 87 Carcinogenic, 80, 96, 103 Carcinogens, 80, 84 Carcinoma, 43, 80 Cardiac, 8, 19, 28, 38, 76, 77, 80, 83, 86, 95, 103 Cardiopulmonary, 19, 80 Cardiopulmonary Bypass, 19, 80 Cardioselective, 78, 80, 100 Cardiovascular, 34, 42, 50, 80, 102 Cardiovascular disease, 42, 80 Caspase, 19, 80 Cause of Death, 41, 80 Cell, 14, 32, 33, 43, 77, 78, 79, 80, 81, 82, 84, 86, 89, 90, 91, 92, 94, 95, 98, 99, 100, 101, 105 Cell Cycle, 14, 33, 81 Cell Death, 32, 77, 81, 95 Cell Division, 78, 81, 94, 99 Cellobiose, 81 Cellulose, 45, 81, 99 Central Nervous System, 75, 81, 95, 98, 102 Centrifugation, 81, 94 Cerebral, 9, 81, 86 Cerebrotendinous Xanthomatosis, 5, 81 Cerebrovascular, 80, 81 Cerebrum, 81 Chemotherapy, 43, 81 Chenodeoxycholic Acid, 5, 81 Choleretic, 81 Cholestanol, 4, 6, 33, 81 Cholesterol Esters, 81, 92 Cholestyramine, 42, 81 Chromatin, 77, 81 Chylomicrons, 81, 93 Citric Acid, 45, 82 Citrus, 78, 82 Claudication, 11, 13, 82 Clinical Medicine, 18, 82, 99 Clinical study, 82, 83 Clinical trial, 4, 27, 59, 82, 83, 101 Cloning, 79, 82 Coenzyme, 6, 16, 29, 30, 35, 42, 45, 78, 82, 93, 103 Colestipol, 42, 82 Complement, 82, 83

Complementary and alternative medicine, 27, 36, 82 Complementary medicine, 27, 83 Computational Biology, 59, 83 Computed tomography, 30, 83 Computerized axial tomography, 83 Computerized tomography, 83 Concomitant, 8, 83 Conjugated, 78, 81, 83, 84 Connective Tissue, 78, 79, 83, 87 Contraindications, ii, 83 Controlled clinical trial, 20, 83 Controlled study, 19, 83 Coordination, 83, 95 Cornea, 81, 83 Coronary, 6, 7, 9, 11, 12, 14, 15, 16, 19, 27, 28, 30, 32, 33, 41, 42, 50, 80, 83, 84, 94, 95 Coronary Artery Bypass, 7, 28, 83 Coronary Disease, 50, 83 Coronary heart disease, 11, 15, 27, 32, 41, 42, 80, 84 Coronary Thrombosis, 84, 94, 95 Coronary Vessels, 84 Curative, 84, 96, 104 Cutaneous, 80, 84, 106 Cyclic, 44, 84, 88, 96, 100 Cytochrome, 18, 84 Cytochrome P-450, 18, 84 Cytoplasm, 77, 84, 88, 95 D Dairy Products, 84, 102 Databases, Bibliographic, 59, 84 Degenerative, 84, 89 Deletion, 77, 84 Density, 4, 11, 60, 78, 81, 84, 85, 92, 93, 96 Depressive Disorder, 84, 93 Dermatitis, 8, 85 Deuterium, 85, 89 Diagnostic procedure, 37, 51, 85 Dialyzer, 85, 89 Diarrhea, 81, 85, 92 Dietary Fats, 85, 92 Digestion, 78, 79, 85, 92, 93, 103 Dihydrotestosterone, 85, 101 Dihydroxy, 41, 42, 85 Dilatation, 77, 85, 105 Dilatation, Pathologic, 85, 105 Dilation, 18, 80, 85, 105 Dilator, 30, 85 Direct, iii, 40, 44, 53, 82, 85, 101 Distal, 83, 85 Dosage Forms, 45, 85

Index 109

Drug Interactions, 54, 85 Duke, 24, 85 Duodenum, 78, 85, 103 Dyes, 77, 85 Dyslipidemia, 3, 60, 85 E Edema, 86, 95, 96 Efficacy, 3, 7, 9, 10, 13, 16, 18, 22, 24, 31, 42, 60, 86 Electrolytes, 78, 86 Electrons, 77, 78, 86, 92, 97, 101 Enalapril, 12, 86 Endothelium, 86, 96 Endothelium-derived, 86, 96 Environmental Health, 58, 60, 86 Enzymatic, 44, 80, 82, 86, 87 Enzyme, 38, 40, 44, 80, 82, 86, 87, 88, 92, 93, 95, 96, 100, 101, 103, 104, 105 Epidemic, 43, 86 Epinephrine, 75, 86, 105 Erythrocytes, 6, 79, 86 Estrogen, 20, 86 Ethanol, 86, 87 Ether, 44, 86 Exogenous, 31, 79, 86, 104 Extracellular, 77, 83, 86, 87 F Family Planning, 59, 86 Fat, 5, 75, 77, 78, 79, 84, 87, 92, 95, 96, 97, 99, 102, 104 Fatty acids, 87, 100, 106 Feces, 81, 87 Femoral, 17, 80, 87 Femoral Artery, 17, 80, 87 Femur, 87 Fermentation, 38, 39, 40, 87 Fibrillation, 8, 87 Fibrin, 79, 87, 104 Fibrinogen, 11, 87, 104 Fibrinolytic, 19, 87 Fibroblasts, 87, 91 Fluconazole, 20, 87 Fluoxetine, 12, 87 Foam Cells, 87, 106 Fold, 87, 94 G Gallbladder, 75, 79, 87 Gallstones, 31, 79, 81, 87 Gas, 76, 87, 89, 92, 96, 105 Gastric, 85, 87 Gastrin, 87, 89 Gelatin, 87, 88, 104

Gemfibrozil, 3, 60, 88 Gene, 79, 84, 88, 90 Genetics, 5, 20, 88 Genotype, 88, 98 Gland, 88, 97, 100, 104 Glioma, 17, 33, 88 Glucose, 78, 79, 81, 88, 89, 91, 102 Glucuronic Acid, 88, 89 Glycine, 78, 81, 88, 102 Glycoprotein, 24, 87, 88 Gonadal, 88, 103 Governing Board, 88, 99 Graft, 88, 89, 90, 95 Graft Rejection, 88, 90 Grafting, 7, 28, 83, 88 Granulocytes, 88, 92, 106 Growth, 77, 81, 88, 91, 94, 98, 104 Guanylate Cyclase, 88, 96 H Heart attack, 80, 88 Heart Transplantation, 19, 64, 88 Heme, 79, 84, 88 Hemodialysis, 8, 85, 89 Hemoglobin, 86, 88, 89 Hemorrhage, 89, 95, 103 Heparin, 24, 89 Hepatic, 5, 9, 22, 29, 31, 89, 93, 103 Hepatitis, 43, 89, 105 Hepatocellular, 43, 89 Hepatocellular carcinoma, 43, 89 Hepatocytes, 89 Hepatotoxicity, 14, 89 Heredity, 88, 89 Hormone, 10, 29, 86, 87, 89, 91, 100, 103, 104 Host, 78, 89, 90, 105 Hybridomas, 89, 91 Hydrogen, 44, 75, 76, 78, 85, 89, 92, 94, 96, 97, 98, 101 Hydrogen Peroxide, 89, 92 Hydrolysis, 11, 79, 81, 89, 99, 101 Hydrophobic, 90, 92 Hypercholesterolemia, 3, 5, 11, 12, 13, 14, 15, 16, 17, 18, 31, 33, 35, 38, 39, 41, 60, 85, 90 Hyperlipidaemia, 31, 90 Hyperlipidemia, 3, 5, 9, 11, 20, 30, 50, 60, 85, 90 Hyperlipoproteinemia, 12, 90, 93 Hypertension, 80, 86, 90, 100 Hypertriglyceridemia, 13, 85, 90 Hypoglycemic, 3, 60, 90

110 Zocor

Hypoglycemic Agents, 3, 60, 90 I Id, 25, 34, 64, 70, 72, 90 Idiopathic, 27, 90 Iliac Artery, 87, 90 Immune response, 78, 88, 90, 103, 105 Immune system, 90, 93, 95, 105 Immunity, 90, 96 Immunization, 90, 100 Immunosuppressive, 90 Immunosuppressive therapy, 90 Immunotherapy, 43, 90 Impairment, 30, 90, 94 In vitro, 6, 9, 29, 32, 90 In vivo, 6, 8, 19, 89, 90 Incontinence, 90, 97 Indicative, 47, 91, 97, 105 Induction, 91, 103 Infarction, 84, 91, 94, 95, 100, 101 Infection, 80, 91, 103, 105 Inflammation, 51, 77, 78, 85, 89, 91, 94 Ingestion, 5, 91 Inotropic, 78, 91 Insulator, 91, 95 Insulin, 3, 30, 35, 60, 91, 104 Insulin-dependent diabetes mellitus, 91 Interleukin-1, 13, 91 Interleukin-2, 91 Interleukin-6, 19, 91 Intermittent, 11, 13, 91, 98 Intestinal, 28, 81, 91, 93 Intestines, 75, 87, 91 Intracellular, 91, 96, 100 Invasive, 90, 92, 93 Involuntary, 87, 92, 95, 106 Ions, 78, 81, 86, 89, 92 Irritable Bowel Syndrome, 92, 97 Ischemia, 92, 95, 101 K Kb, 58, 92 Ketoconazole, 18, 92 L Latent, 29, 92 Laxative, 76, 81, 92 Lesion, 83, 92 Leucocyte, 19, 92 Leukocytes, 79, 88, 92, 95 Library Services, 70, 92 Ligament, 92, 100 Lipase, 5, 12, 92, 96 Lipid, 3, 12, 14, 15, 16, 31, 32, 42, 60, 77, 78, 87, 88, 91, 92, 95, 97, 104, 105, 106

Lipid A, 92, 97 Lipid Peroxidation, 12, 31, 92, 97 Lipophilic, 12, 92 Lipopolysaccharide, 19, 92 Lipoprotein, 4, 5, 30, 60, 85, 92, 93 Lipoprotein Lipase, 5, 93 Lithium, 38, 40, 93 Liver, 8, 15, 32, 43, 75, 77, 78, 79, 87, 88, 89, 93 Liver cancer, 43, 93 Liver Cirrhosis, 43, 93 Liver Transplantation, 43, 93 Localized, 43, 91, 93, 98, 99 Longitudinal study, 11, 93 Lovastatin, 6, 18, 26, 38, 39, 40, 41, 42, 44, 45, 93, 103 Low-density lipoprotein, 7, 9, 16, 32, 85, 93 Lymphoid, 92, 93 M Macrophage, 91, 93 Magnetic Resonance Imaging, 16, 93 Malabsorption, 33, 93 Malignancy, 43, 93 Malignant, 43, 75, 93, 94 Malignant tumor, 43, 94 Mammary, 83, 93, 94 Manic, 93, 94 Meat, 85, 94, 102 MEDLINE, 59, 94 Melanin, 94, 98, 105 Meningitis, 87, 94 Menopause, 94, 99, 100 Mental Disorders, 94, 99 Mental Health, iv, 4, 58, 61, 94, 99, 101 Mesenteric, 28, 94 Mesentery, 94, 98 Mesothelial, 19, 94 Metabolite, 79, 93, 94, 99 MI, 7, 28, 50, 73, 94 Microbe, 94, 104 Microcirculation, 93, 94 Microorganism, 94, 105 Microsomal, 29, 94 Mitosis, 77, 94 Molecular, 24, 31, 59, 62, 79, 83, 87, 89, 94 Molecule, 40, 44, 75, 78, 82, 86, 89, 94, 97, 101 Monocytes, 19, 20, 87, 91, 92, 95 Mononuclear, 95 Multiple sclerosis, 50, 95 Mutagens, 84, 95

Index 111

Mydriatic, 85, 95 Myelin, 95 Myocardial Ischemia, 84, 95 Myocardial Reperfusion, 95, 102 Myocardial Reperfusion Injury, 95, 102 Myocardium, 94, 95 Myopathy, 8, 95 N Nausea, 85, 95 Necrosis, 77, 91, 94, 95, 101, 102 Need, 3, 38, 39, 42, 47, 60, 65, 75, 95 Nelfinavir, 6, 21, 96 Nephropathy, 27, 96 Nephrosis, 96 Nephrotic, 27, 96 Nephrotic Syndrome, 27, 96 Nerve, 75, 95, 96, 102 Neutrons, 76, 96, 101 Niacin, 28, 42, 50, 96 Nitric Oxide, 12, 34, 96 Nitrogen, 76, 96 Nuclei, 76, 86, 93, 94, 96, 101 Nucleus, 44, 77, 81, 84, 85, 95, 96, 101 O Ointments, 85, 96 Omega-3 fatty acid, 30, 31, 96 Oncogenic, 43, 96 Opacity, 84, 96 Ophthalmologic, 85, 96 Organelles, 81, 84, 95, 96 Orlistat, 12, 96 Outpatient, 97 Oxidation, 75, 77, 79, 84, 92, 97 Oxidative Stress, 10, 97 Oxygenator, 80, 97 P Palliative, 97, 104 Pancreas, 75, 91, 92, 97 Pancreatic, 19, 97 Particle, 31, 97 Patch, 20, 97, 104 Pathologic, 75, 77, 79, 83, 97 Pathologic Processes, 77, 97 Pelvic, 97, 100 Perfusion, 30, 97 Peripheral Vascular Disease, 13, 97 Peritoneal, 18, 19, 24, 97, 98 Peritoneal Cavity, 97, 98 Peritoneal Dialysis, 18, 24, 98 Peritoneum, 94, 97, 98 PH, 6, 10, 30, 98

Pharmaceutical Preparations, 81, 86, 87, 98 Pharmaceutical Solutions, 85, 98 Pharmacokinetic, 6, 15, 98 Pharmacologic, 98, 104 Phenobarbital, 84, 98 Phenotype, 4, 60, 98 Phenylalanine, 98, 105 Phospholipids, 87, 92, 98 Phosphorus, 80, 98 Phosphorylated, 82, 98 Phosphorylation, 32, 98 Physiologic, 79, 98, 100, 101 Plants, 82, 88, 98, 99, 102, 105 Plaque, 21, 99 Plasma, 10, 11, 12, 20, 31, 32, 42, 81, 87, 89, 90, 99, 102, 106 Platelet Aggregation, 96, 99 Platelets, 96, 99, 102 Pleural, 94, 99 Polymorphism, 18, 22, 99 Polypeptide, 87, 99 Polysaccharide, 81, 99 Polyunsaturated fat, 27, 99 Postmenopausal, 11, 20, 99 Postoperative, 7, 28, 99 Postprandial, 30, 31, 99 Potentiates, 91, 99 Potentiation, 14, 99 Practice Guidelines, 61, 99 Pravastatin, 8, 10, 13, 14, 16, 18, 26, 29, 40, 42, 45, 99 Precursor, 5, 22, 77, 86, 98, 99, 105 Primary Prevention, 10, 99 Progesterone, 100, 103 Progestogen, 20, 100 Progression, 38, 50, 100 Prophylaxis, 38, 100 Propranolol, 78, 100 Prospective study, 93, 100 Prostaglandin, 21, 100 Prostaglandins A, 100 Prostate, 18, 100 Protease, 96, 100 Protein C, 77, 78, 92, 100 Protein S, 79, 101 Proteins, 76, 77, 80, 81, 82, 91, 94, 96, 99, 101, 102, 104, 105 Proteinuria, 96, 101 Proteolytic, 82, 87, 101 Protons, 76, 89, 101 Public Health, 43, 61, 101

112 Zocor

Public Policy, 59, 101 Publishing, 6, 101 Pupil, 83, 85, 95, 101 Purines, 101, 102 R Radiation, 43, 101, 106 Radioactive, 79, 89, 96, 101 Randomized, 7, 10, 13, 19, 20, 24, 29, 30, 86, 101 Receptor, 15, 98, 101, 102 Rectum, 87, 90, 100, 101 Reductase, 6, 13, 26, 29, 30, 31, 32, 38, 39, 40, 41, 42, 44, 45, 54, 93, 99, 101, 103 Refer, 1, 82, 96, 101 Regimen, 86, 101 Reperfusion, 34, 95, 101, 102 Reperfusion Injury, 34, 102 Resection, 43, 102 Rhabdomyolysis, 14, 18, 20, 21, 22, 102 Risk factor, 12, 30, 38, 41, 42, 50, 100, 102 S Saphenous, 83, 102 Saphenous Vein, 83, 102 Saponins, 102, 103 Saturated fat, 42, 102 Sclerosis, 78, 95, 102 Screening, 82, 102 Semen, 100, 102 Serine, 19, 102 Serotonin, 87, 102 Serum, 6, 9, 11, 15, 16, 17, 21, 30, 32, 33, 38, 44, 82, 88, 93, 102 Shock, 10, 102 Side effect, 8, 15, 21, 53, 75, 102, 104 Skeletal, 102, 103 Skeleton, 87, 100, 103 Small intestine, 79, 81, 82, 85, 89, 91, 103 Smooth muscle, 10, 34, 76, 87, 103 Soybean Oil, 99, 103 Specialist, 65, 85, 103 Species, 40, 86, 94, 103, 104, 105 Spectrum, 92, 103 Spinal cord, 79, 81, 103 Stabilization, 21, 103 Steroid, 10, 29, 78, 102, 103 Stomach, 75, 87, 89, 91, 95, 98, 103 Stroke, 51, 58, 64, 80, 103 Subclinical, 10, 91, 103 Subspecies, 103 Substance P, 94, 100, 103 Supplementation, 27, 31, 104 Symphysis, 100, 104

Systemic, 54, 77, 79, 80, 86, 91, 104, 105 T Talc, 45, 104 Taurine, 78, 81, 104 Testosterone, 101, 104 Therapeutics, 7, 9, 18, 21, 22, 29, 54, 104 Thigh, 87, 104 Threonine, 19, 102, 104 Thrombin, 87, 99, 100, 104 Thrombosis, 20, 28, 30, 31, 33, 101, 103, 104 Thyroid, 104, 105 Tissue, 18, 75, 76, 79, 80, 83, 86, 87, 88, 90, 92, 93, 94, 95, 96, 97, 99, 101, 102, 104 Tomography, 7, 10, 28, 32, 104 Toxic, iv, 90, 104 Toxicity, 29, 85, 104 Toxicology, 60, 104 Transdermal, 20, 104 Transfection, 79, 104 Transplantation, 19, 43, 90, 104 Triglyceride, 4, 5, 7, 60, 82, 90, 104 Tumour, 104, 106 Type 2 diabetes, 3, 60, 104 Tyrosine, 32, 105 U Ubiquinone, 31, 105 Unconscious, 90, 105 Urethra, 100, 105 Urinary, 18, 90, 105 Urine, 5, 79, 90, 101, 105 V Vaccines, 105 Vascular, 12, 20, 28, 30, 31, 33, 34, 76, 86, 91, 93, 94, 96, 105 Vascular Resistance, 76, 105 Vasodilation, 12, 105 Vasodilator, 30, 80, 95, 105 VE, 17, 105 Ventricular, 76, 95, 105 Vesicular, 94, 105 Veterinary Medicine, 59, 105 Viral, 43, 96, 105 Viral Hepatitis, 43, 105 Virulence, 104, 105 Virus, 43, 78, 99, 105 Vitro, 89, 105 Vivo, 34, 105 W White blood cell, 5, 92, 93, 105 X Xanthoma, 5, 106

Index 113

Xanthomatosis, 28, 106 X-ray, 83, 106

Y Yawning, 17, 24, 106 Yeasts, 98, 106

114 Zocor

Index 115

116 Zocor

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