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

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

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DILTIAZEM 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., 1960Diltiazem: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00368-6 1. Diltiazem-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 diltiazem. 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 DILTIAZEM ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Diltiazem....................................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 12 The National Library of Medicine: PubMed ................................................................................ 13 CHAPTER 2. NUTRITION AND DILTIAZEM ...................................................................................... 59 Overview...................................................................................................................................... 59 Finding Nutrition Studies on Diltiazem ..................................................................................... 59 Federal Resources on Nutrition ................................................................................................... 61 Additional Web Resources ........................................................................................................... 62 CHAPTER 3. ALTERNATIVE MEDICINE AND DILTIAZEM ................................................................ 63 Overview...................................................................................................................................... 63 National Center for Complementary and Alternative Medicine.................................................. 63 Additional Web Resources ........................................................................................................... 68 General References ....................................................................................................................... 70 CHAPTER 4. PATENTS ON DILTIAZEM............................................................................................. 71 Overview...................................................................................................................................... 71 Patents on Diltiazem.................................................................................................................... 71 Patent Applications on Diltiazem................................................................................................ 86 Keeping Current .......................................................................................................................... 93 CHAPTER 5. BOOKS ON DILTIAZEM ................................................................................................ 95 Overview...................................................................................................................................... 95 The National Library of Medicine Book Index ............................................................................. 95 Chapters on Diltiazem ................................................................................................................. 96 CHAPTER 6. PERIODICALS AND NEWS ON DILTIAZEM .................................................................. 99 Overview...................................................................................................................................... 99 News Services and Press Releases................................................................................................ 99 Academic Periodicals covering Diltiazem.................................................................................. 101 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 103 Overview.................................................................................................................................... 103 U.S. Pharmacopeia..................................................................................................................... 103 Commercial Databases ............................................................................................................... 104 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 107 Overview.................................................................................................................................... 107 NIH Guidelines.......................................................................................................................... 107 NIH Databases........................................................................................................................... 109 Other Commercial Databases..................................................................................................... 111 APPENDIX B. PATIENT RESOURCES ............................................................................................... 113 Overview.................................................................................................................................... 113 Patient Guideline Sources.......................................................................................................... 113 Finding Associations.................................................................................................................. 115 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 117 Overview.................................................................................................................................... 117 Preparation................................................................................................................................. 117 Finding a Local Medical Library................................................................................................ 117 Medical Libraries in the U.S. and Canada ................................................................................. 117 ONLINE GLOSSARIES................................................................................................................ 123 Online Dictionary Directories ................................................................................................... 123

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DILTIAZEM DICTIONARY........................................................................................................ 125 INDEX .............................................................................................................................................. 185

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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 diltiazem is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about diltiazem, 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 diltiazem, 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 diltiazem. 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 diltiazem, 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 diltiazem. 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 DILTIAZEM Overview In this chapter, we will show you how to locate peer-reviewed references and studies on diltiazem.

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

How to Best Control Hypertension in Patients with Renal Insufficiency Source: Journal of Critical Illness. 15(9): 468. September 2000. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Greenwich, CT 06831-0010. (203) 661-0600. Summary: In general, the same drugs used in patients with essential hypertension (high blood pressure) who have normal kidney function can be used in patients with hypertension and chronic renal insufficiency (CRI), including particular drugs when there are other comorbid conditions. This brief article reviews the clinical strategies for controlling hypertension in patients with renal insufficiency. The author notes two specific recommendations from the Joint National Committee (JNC VI): blood pressure should be lowered to 130 over 85 mm Hg; and patients with hypertension who have CRI

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should receive, unless contraindicated, an ACE inhibitor to control hypertension and to slow the progression of renal failure. The author cautions against the use of alpha adrenergic blockers, which have been associated with significant orthostatic hypotension (low blood pressure), particularly in patients with autonomic neuropathy (nerve damage) associated with CRI. ACE inhibitors should be used cautiously in patients with proven or suspected renal artery disease, since these agents may precipitate an acute loss of kidney function; if this occurs in a patient in whom renal artery stenosis has not been suspected previously, the diagnosis should be considered. Diuretics are the second choice drugs (after ACE inhibitors). A calcium channel blocker (diltiazem or verapimil) can be added if needed to achieve goal blood pressure. 1 figure. 2 references. •

Are Calcium Antagonists Effective in Preventing Complications of Hypertension and Progression of Renal Disease? Source: Current Opinion in Nephrology and Hypertension. 9(5): 489-495. September 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: Long acting calcium antagonists have been shown to be safe and effective in lowering blood pressure, both as first line agents and in combination with other classes of antihypertensive drug. This article explores recent research exploring whether calcium antagonists are effective in preventing complications of hypertension and progression of renal disease. Calcium antagonists have been shown to reduce the incidence of cerebrovascular and cardiovascular events in elderly patients with predominantly systolic hypertension (high blood pressure). It is clear that reduced morbidity and mortality in hypertension is related to the degree to which blood pressure is reduced, regardless of the therapy used. This is the single most important conclusion of all recent trials, especially in the subgroup of hypertensive patients with diabetes. The World Health Organization (WHO) International Society of Hypertension guidelines acknowledge this and do not make specific recommendations as to initial therapy in the absence of other medical factors. However, the use of thiazide diuretics and beta blockers has strong support from large placebo controlled trials in patients with mild to moderate essential hypertension. The British Hypertension Society and JNC VI guidelines restrict their recommendations for the use of calcium antagonists to isolated systolic hypertension and angina, or when other agents have failed, are contraindicated, or are not tolerated. However, the efficacy of calcium antagonists in lowering blood pressure, their tolerability and potentially beneficial secondary effect on proteinuria (protein in the urine), especially in combination with an ACE inhibitor, still make them attractive antihypertensive agents. Unlike ACE inhibitors, the antiproteinuric effect of calcium antagonists, even that of the non dihydropyridine type, seems to depend on an adequate and stable reduction in blood pressure. Calcium channel blockers include nifedipine, amlodipine, verapamil, and diltiazem. 5 figures. 52 references.

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Calcium Channel Blockers: A Unique Group of Antihypertensives Source: For Patients Only. 6(4): 16-17. July/August 1993. Summary: This article discusses calcium channel blockers, agents that are used to treat hypertension, to relieve the chest pain of angina, or to treat certain heart irregularities.

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Nine drugs are discussed: amlodipine (Norvasc), bepridil (Vascor), diltiazem (Cardizem), felodipine (Plendil), isradipine (Dynacirc), nicardipine (Cardene), nifedipine (Procardia), nimodipine (Nimotop), and verapamil (Calan, Isoptin, Verelan). Topics include sustained-release dosage; side effects of calcium channel blockers; and drug interactions. •

Drugs Used to Manage Cardiovascular Disease: Part V-Calcium Channel Blockers Source: Access. 15(7): 38-40. August 2001. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: This article in one in a series that familiarizes dental hygienists with the drugs that may be use to manage cardiovascular disease; this fifth entry in the ongoing series focuses on calcium channel blockers. The series addresses the classes of medications used to manage a variety of cardiac conditions, including hypertension (HTN), angina, myocardial infarction, arrhythmias, heart murmurs, and stroke. Drug interactions, oral side effects, and general side effects of these cardiac medications are discussed, along with recommendations for client management and risk assessment strategies. In this article, the author focuses on calcium channel blockers (CCBs), which are divided into three main chemical classes: benzothiazepines, including diltiazem (Cardizem, Dilacor); diphenylalkylamines, notably verapamil (Calan); and dihydropyridines, including nifedipine (Procardia, Adalat), amlodipine (Norvasc), felodipine (Plendil), isradipine (DynaCirc), nicardipine (Cardene), and nisoldipine (Sular). Two additional drugs are discussed: bepridil (Vascor) and nimodipine (Nimotop). Gingival hyperplasia (gum overgrowth) occurs with some of these CCBs, including nifedipine, diltiazem, verapamil, and amlodipine. Good oral hygiene may help to limit the degree of severity of overgrowth; however, plaque control will not prevent overgrowth from occurring. One chart summarizes drug interactions with calcium channel blockers. 2 tables. 16 references.

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Treatment of Elevated Blood Pressure in Diabetic Patients Source: Journal of Diabetes and Its Complications. 11(2): 92-99. March-April 1997. Contact: Available from Elsevier Science, Inc. Journal Fulfillment Department, 655 Avenue of the Americas, New York, NY 10010. (212) 633-3950. Fax (212) 633-3990. Summary: This article outlines lifestyle modifications that can form the basis of hypertension prevention and treatment in people with diabetes. Arterial hypertension is a major contributor to the secondary complications of diabetes. Moreover, prevention or treatment of hypertension reduces the incidence and progression of diabetes complications. Lifestyle modifications include weight management, nutrient modifications, physical activity, moderation of alcohol ingestion, and smoking cessation. The authors also discuss the potential advantages and disadvantages of each type of antihypertensive drug. Conventional therapy with thiazide-type or loop diuretics and or beta blockers can aggravate metabolic alterations. In reducing diabetic microalbuminuria or overt proteinuria, ACE inhibitors are more effective than conventional diuretics or beta blockers. ACE inhibitors also tend to preserve glomerular filtration rate (GFR) better than conventional antihypertensive drugs or nifedipine. The combination of an ACE inhibitor with a calcium antagonist such as verapamil or diltiazem can be more effective in reducing proteinuria and slowing the course of nephropathy than when each drug is used alone. The authors note that little information is available on the common problem of how to treat individuals with diabetes who have

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hypertension resistant to different drug combinations, including diuretics in the recommended low doses. The authors present a case study and synopsis in which they discuss this issue. 3 figures. 3 tables. 45 references. (AA-M). •

Gingival Inflammatory Infiltrate in Cardiac Patients Treated with Calcium Antagonists Source: Journal of Clinical Periodontology. 28(9): 897-903. September 2001. Contact: Available from Munksgaard International Publishers Ltd. Commerce Place, 350 Main Street, Malden, MA 02148-5018. (781) 388-8273. Fax (781) 388-8274. Summary: This article reports on a study undertaken to analyze the periodontal inflammatory infiltrates in patients with cardiac disease. In the study, some of the patients were treated with calcium antagonists (nifedipine and diltiazem) and some were not; patients were compared with a healthy control group, and the authors evaluated the changes in the inflammatory infiltrate after periodontal treatment. A 'healthy group' (HG, n = 12), a 'cardiac group' (CG, n = 12), without treatment with calcium antagonists, a 'nifedipine group' (NG, n = 18), and a 'diltiazem group' (DG, n = 13) were analyzed. Biopsies were taken before causal periodontal treatment and after 1 year. When the cells were compared statistically, differences were established for lymphocytes at the first visit and at the last visit, for the B lymphocytes and for the T lymphocytes. Between the 2 visits, HG showed significant reductions for plasma cells, lymphocytes, and histiocytes; and the NG for lymphocytes. Lymphocytes showed differences in the NG with respect to the B lymphocytes. The authors conclude that nifedipine affects the inflammatory infiltrate with a greater number of lymphocytes (especially B) and these cells fell significantly in number after periodontal treatment. 6 figures. 4 tables. 24 references.

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

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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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Project Title: ALCOHOL MODULATION OF CARDIAC CALCIUM CHANNELS Principal Investigator & Institution: Aistrup, Gary L.; Mol Pharm & Biol Chemistry; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Alcohol exerts a variety of actions on the cardiovascular system, the nervous system, and other organs. Clinical studies, have linked alcohol consumption with a number of asymptomatic and overt cardiovascular abnormalities, including cardiomyopathy, hypertension, arrhythmias, heart failure, and stroke. The mechanisms responsible for these various problems are not well understood. In the nervous system, voltage activated calcium channels and certain ligand-gated channels arc particularly sensitive targets of alcohol. These channels are suspected of being instrumental in acute intoxication and withdrawal. In cardiac tissues, calcium channels play a key role in rhythmicity, conduction, and excitation-contraction coupling. These channels are a major site of control by endogenous hormones and transmitters, and by therapeutic drugs. Calcium channels have been directly linked to a number of the actions of ethanol on the heart. Ethanol interferes with contractility in a variety of models, and it reduces electrically-stimulated calcium transients in ventricular myocytes. Our preliminary data with rat myocytes, and results from other laboratories, have confirmed that ethanol blocks L-type calcium channels in isolated cardiac cells. Defining how alcohol affects the physiology and regulation of these channels is essential in explaining immediate consequences of alcohol ingestion, as well as events that occur during prolonged periods of alcohol ethanol abuse. The overall objective of the proposed studies is to use whole-cell patch clamp techniques to analyze ethanol modulation of cardiac calcium channels. Ventricular myocytes will be dissociated from cardiac tissues of adult rats, and subjected to acute alcohol exposure. Biophysical and pharmacological experiments will evaluate calcium channel function under these conditions, and impossible mechanisms of channel modulation. Certain second messenger systems are known to exert regulatory control over calcium channel function in heart cells. Among these, the betaadrenergic/cAMP/PKA pathway is a critical mechanism for enhancing L-type calcium channels and stimulating cardiac contractility. We will therefore test the hypothesis that ethanol alters regulation of channels through this signal transduction system. Our preliminary data have shown that ethanol not only blocks currents stimulated via the beta-adrenergic system, but it also inhibits desensitization of the coupling process. We have also just completed exciting new preliminary studies demonstrating that ethanol is capable of reversing or occluding nifedipine-induced channel block. This novel action may have major implications, given the widespread clinical use of dihydropyridines and other calcium channel antagonists. Drug interactions of this type will be an important focus of the project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATRIAL FIBRILLATION FOLLOW UP OF RHYTHM MANAGEMENT (AFFIRM) Principal Investigator & Institution: Pritchett, Edward L.; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CALCIUM CHANNEL GATING: IT MATTERS HOW YOU SPLICE IT. Principal Investigator & Institution: Horne, William A.; Vet Biomedical Sciences; Colorado State University-Fort Collins Fort Collins, Co 80523 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term goal of this project is to understand how voltage-gated Ca2+ channels sense and decode electrical and molecular signals that regulate neurotransmitter release. Ca2+ channels are large (about 370 kDa) heteromultimeric proteins composed of alpha1, alpha2delta, and beta subunits that work in concert to control the amount of Ca2+ that enters a neuron in response to a given stimulus. The subunits form the Ca2+ channel pore (4 large transmembrane homology domains) and are encoded by at least ten genes that, based on structural, electrophysiological, and pharmacological differences, can be divided into three major sub-groups, Cav1, Cav2 and Cav3. Cav1 and Cav2 are high-voltage activating channels, whereas Cav3 channels activate at more negative membrane potentials. Cav1 genes express channels with L-type (long lasting) electrophysiological characteristics, Cav2 genes express P/Q, N, and R-type (intermediate lasting) channels, and Cav3 genes express T-type (transient) channels. The alpha1 subunits serve as targets for several classes of therapeutic agents, including antiarrhythmics (diltiazem, L-type antagonist) and analgesics (ziconotide, N-type antagonist from a marine snail), and for a host of peptide spider toxins (e.g., Aga IVA, P-type antagonist). Cav2 genes, which will be studied in this proposal, are expressed principally at synapses.The intracellular beta subunits, encoded by 4 distinct genes, interact with the alpha1 subunit at specific binding sites on between-homology-domain linker sequences. The beta subunits modulate Ca2+ channel expression levels, as well as the voltage dependence and kinetics of Ca2+ channel activation and inactivation. Our preliminary studies show that alternative splicing of the N-terminus of the beta4 subunit has alpha1 subunit subtypespecific effects on Ca2+ channel gating. They also show that splicing affects channel pharmacology (altered sensitivity to omegaCgTx GVIA) and responsiveness of alpha1 subunits to repetitive stimuli. Thus, understanding the molecular details of the events brought about by beta4 alternative splicing is essential for the development of analgesic drugs, and for furthering our understanding of the role that voltage-gated Ca2+ channels play in synaptic plasticity. To this end, our most remarkable preliminary result, obtained by using simple methods in structural genomics, is the discovery that the beta4 subunit and the synaptic scaffolding (MAGUK) protein, PSD-95, have evolved from a common ancestor. The two proteins share very similar predicted secondary structure, and with the crystal structure of PSD-95 now available, a number of beta4 subunit tertiary structure predictions can now be made. The objectives of this application are to confirm, using advanced NMR techniques, our tertiary structure predictions and to determine whether the well-characterized inter- and intramolecular interactions of PSD-95 have been conserved in beta4 subunits. Our hypothesis is that the beta4 subunit acts as a multi-modular docking site for a myriad of proteins, including calmodulin, kinase anchoring proteins, and PDZ domains, and serves as a director, transmitting molecular signals from inside the cell to the gating machinery of alpha1 subunits Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONSEQUENCES OF DRUG COST SHARING IN THE ELDERLY Principal Investigator & Institution: Schneeweiss, Sebastian; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 28-FEB-2003

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Summary: This observational study takes advantage of a natural experiment and comprehensive health care data in the province of British Columbia to examine the effects, intended and unintended, of a policy of differential cost-sharing (reference pricing) for prescription drugs implemented on Jan 1, 1997. Two classes of drugs, ACE inhibitors (ACEIs) and calcium-channel blockers (CCBs), are studied. Outcomes include utilization of several categories of health care, total costs of care, and adverse outcomes (cardiovascular disease hospitalizations and mortality). The underlying study population includes approximately 445,000 persons aged 65 years of age and over on Jan 1 1995. Of these, about 160,000 appear to have received one of the cost-sharing drugs during the baseline period and would therefore be included in the analyses. Interrupted time-series analyses are proposed to control for secular trends in utilization and event rates among persons. Three control groups will also be studied: historical controls (persons using the same drugs, but identified and followed beginning one year earlier); concurrent controls on a non-cost-sharing drug (diltiazem); and external controls, drawn from users of the same cost-sharing drugs but from another province, Ontario, where cost-sharing was not introduced. Primary analyses are conducted for the entire population of users of these medications. For several policy-related reasons, relatively small fractions of these patients (slightly less than 25%) appear to have switched to low cost alternative ACEIs or CCBs or to have stopped their previously used medications altogether. Thus, effects on utilization or increasing rates of adverse events may be difficult to detect in the entire population. Secondary analyses are therefore proposed that will compare post-implementation rates in "switchers" versus "non-switchers". The investigators recognize that these secondary analyses introduce the strong likelihood of confounding by indication (switchers are very likely to differ in risk from non-switchers) and they propose to use comorbidity adjusters (a pharmacy-based chronic disease score, and a diagnosis-based casemix adjustment measure), and multiple patient and physician characteristics. These confounders will be adjusted for using a propensity score (propensity to switch or stop the cost-sharing drug). Additional analyses will examine possible changes in prescribing patterns for persons initiating ACEI or CCB treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CELL DEATH IN CARDIOMYOPATHY Principal Investigator & Institution: Kuo, Tuan H.; Professor; Pathology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 30-JUN-2005 Summary: (provided by applicant): The long-term goal of this project is to elucidate the mechanism of Ca2+ -mediated cell death in cardiomyopathy. It is our hypothesis that altered Ca2+ homeostasis and unbalanced signal transduction can lead to mitochondrial dysfunction and cell death. We propose: 1. To study the regulation of mitochondrial Ca2+ (Cam) by the mitochondrial Na/Ca exchanger (NCE) and the permeability transition (MPT) pore in isolated organelle or cultured myocytes. 2. To study the effect of proapoptotic signal transduction on mitochondria by comparing the sensitivity to Ca2+ mediated death and mitochondrial function (Cam load, delta psi, NCE activity and MPT) in cells that overexpress the stress-activated kinase JNK with cells that expressing mutant inactive-JNK. 3. To study the development of cardiomyopathy in the Syrian hamster. The development of lesion in the myopathic heart will be followed at pre-necrotic- (1 mo), necrotic- (2 mo.) and post necrotic- (3 mo.) stage. The changes in the heart will be correlated with studies in isolated myocytes and mitochondria. The parameters to be monitored are mitochondrial Cam load, abnormal NCE activity, JNK/ERK activation, and susceptibility to Ca2+ -induced permeability transition.

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Intervention of cardiomyopathy will be carried out by diltiazem treatment, and heart tissue or mitochondria examined for the prevention of lesion development and for the reversal of abnormal Ca2+ homeostasis and NCE activity. 4. To study the effects of sarcolemmal Na/Ca exchanger (NCX1) overexpression on mitochondrial function and cell injury in transgenic mice. The mechanism for the gender-specific increase in susceptibility to Ca2+ -mediated injury, and the upregulation of mitochondrial NCE activity in association with NCX 1 overexpression will be tested. The direct effect of estrogen (E2) on the activation of growth promoting kinase ERK, and on Ca2+ homeostasis during metabolic stress will also be examined in normal rat myocytes and compared to transgenic myocytes. These studies are designed to advance a poorly understood topic, that is the role of mitochondrial calcium homeostasis and signal transduction in cell survival and cardiomyopathy. We will examine new aspects in the mechanism of cell death and expect the results to be highly relevant to our understanding of gender- specific myocyte function in normal and disease states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC INTESTINAL DRUG INTERACTIONS Principal Investigator & Institution: Thummel, Kenneth E.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: The long-term goal of the research described in this grant proposal is to understand the mechanistic basis for inhibitory drug interactions involving human CYP3A4. This is important for the avoidance of adverse events with the numerous drugs in clinical use today that are either a substrate or inhibitor of the enzyme. It will also aid greatly in predicting the in vivo inhibitory potential for new molecular entities under develop. We hypothesize that effects of several clinically important inhibitory drugs on the first-pass clearance of CYP3A substrate occurs predominantly with the intestinal mucosa, and they can last well beyond the period of inhibitor absorption. This will be investigated with the following Specific Aims: I. To determine whether the inhibitory effect of azole anti-fungals on the first-pass metabolism of the CYP3A marker midazolam occurs predominantly within the intestinal mucosa rather than liver, and whether this preferential inhibition persists will beyond the period of inhibitor absorption due to sequestration of inhibitor in the mucosa. II. To determine whether inhibition of intestinal rather than hepatic first-pass is the predominant mechanism by which dialkylamine inhibitors elevate the systemic availability of orally administered midazolam, and to determine whether the time-course of inhibition parallels the formation of a slowly reversible MI-CYP3A complex. III. To determine if the in vivo effect during multiple dosing of a prototype macrolide inhibitor, erythromycin, an oral midazolam bioavailability, depends on the amount of CYP3A4 expressed in the intestinal mucosa and the accumulation over time of the di-desmethyl erythromycin metabolite in that tissue. We will employ three experimental paradigms; pharmacokinetic studies in healthy human volunteers; in vitro metabolic studies in human-derived Caco-2 cell culture monolayers; and in vivo intestinal extraction studies in a domestic pig model. This three-tiered approach should allow us to identify the contribution of readily predictable, reversible interactions between inhibitor and substrate, and current unpredictable, slowly reversible phenomena such as intracellular inhibitor sequestration and MI complex formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUSCLE PROTEIN TURNOVER AND AMINO ACID UPTAKE IN SEPSIS Principal Investigator & Institution: Hasselgren, Per-Olof J.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-JAN-1987; Project End 31-JUL-2004 Summary: Previous studies suggest that sepsis-induced muscle catabolism reflects ubiquitin-proteasome-dependent degradation of myofibrillar proteins regulated by glucocorticoids. Because intact myofibrils are not degraded by the proteasome, it is possible that actin and myosin are dissociated from the myofibrils before they are ubiquitinated and degraded by the proteasome. We will test the hypotheses: 1) sepsis results in glucocorticoid-mediated calcium/calpain-dependent Z-band disintegration and release of myofilaments in skeletal muscle; 2) sepsis results in increased N-end rule pathway-dependent ubiquitination and breakdown of muscle proteins and upregulated expression and activity of the ubiquitin- conjugating enzyme E2/14k and ubiquitin ligase E3alpha; 3) sepsis- induced muscle cachexia can be inhibited by proteasome blocker in vivo; 4) muscle cachexia in patients with sepsis is associated with increased expression and activity of calpains, release of myofilaments and upregulated protein breakdown in the N-end rule pathway. A septic model in rats consisting of cecal ligation and puncture is used in the majority of experiments. Total and myofibrillar protein breadkdown rates are measured in incubated muscles by determining net release of tyrosine and 3-methylhistidine respectively. Integrity of sarcomeric Z-bands is studied by electron microscopy. Gene and protein expression of calpain and calpastatin are determined by Northern and Western blot analysis, respectively. The role of calcium/calpain-dependent proteolysis is assessed by the effect of dantrolene and diltiazem on sepsis-induced morphologic and metabolic changes. The role of glucocorticoids in sepsis- induced changes in muscle calcium levels and release of myofilaments is determined by the glucocorticoid receptor antagonist RU38486. To test the role of the N-end rule pathway, expression and activity of E2/14k and E3alpha are determined and specific E3albha inhibitors are used in a cell- free system. Similar determinations are performed in muscle from patients with sepsis. The proposal is novel because it suggests that muscle cachexia during sepsis is caused by two distinct mechanisms, i.e., calcium/calpain-dependent release of myofilaments from the sarcomere followed by ubiquitination of myofilaments in the N-end rule pathway and subsequent degradation of ubiquitinated filaments by the 26S proteasome. The hypothesis implies two levels at which sepsis-induced muscle cachexia may be prevented/treated, i.e., inhibition of myofilament release by treatment with a calcium antagonist and inhibition of ubiquitin/proteasome-dependent degradation of the released myofilaments by a proteasome blocker. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POLYCYSTIC KIDNEY DISEASE CLINICAL TRIALS NETWORK Principal Investigator & Institution: Perrone, Ronald D.; Associate Professor; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) is the most common lethal monogenetic disease, affecting 1/500 to 1/1000 of the US population. 50% of those affected with ADPKD will develop end-stage renal disease by the 6th decade of life. There are no proven therapies to slow the inexorable loss of kidney function in those with progressive disease. Interruption of the renin-

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angiotensin-aldosterone system (RAAS) has been shown to reduce the progressive decline in renal function in both diabetic and non-diabetic kidney diseases, but it is unknown whether these results extend to ADPKD. Abundant evidence implicates angiotensin II in the pathogenesis of hypertension, but small single-center studies of limited duration have reported inconsistent results of ACE inhibitor (ACE-I) therapy on disease progression. This application is submitted in response to RFA DK-01-029 to establish a PKD Clinical Trials Network of clinical centers that will each enroll 500 ADPKD patients and conduct a clinical trial to assess the efficacy of therapeutic interruption of the RAAS on renal progression. We have proposed a randomized, double-blinded trial to compare ACE-I vs. active control in hypertensive ADPKD patients with renal insufficiency (GFR 30-65 ml/min/1.73 m2) on the time to reach a composite outcome of doubling of serum creatinine, ESRD, or death. The Clinical Center will be based at the New England Medical Center and Beth Israel Deaconess Medical Center. The Principal and Co-Principal Investigators have had career-long interests in ADPKD and personally care for large numbers of ADPKD patients. We have identified 107 potentially eligible patients within our clinical sites. Additional strategies will be used to target patients locally and within contiguous New England States. Strong institutional support is available at the highest levels, including the General Clinical Research Centers at NEMC and BIDMC. As part of this RFA, we have proposed a pilot study to assess the safety of cyclooxygenase-2 inhibition, which has been implicated in angiogenesis and cyst development in animal models of ADPKD. Thirty ADPKD patients with GFR >70 ml/min/1.73 m2 will be randomized to treatment with celecoxib vs. placebo and followed for 16 weeks. Change in GFR is the primary outcome measure and incidence of hyperkalemia, fluid retention, and elevated blood pressure will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

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Effects of diltiazem on netilmicin-induced nephrotoxicity in rabbits. by Lortholary O, Blanchet F, Nochy D, Heudes D, Seta N, Amirault P, Carbon C.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188072

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

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

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Effects of nifedipine and diltiazem on pharmacokinetics of cefpodoxime following its oral administration. by Deslandes A, Camus F, Lacroix C, Carbon C, Farinotti R.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163639

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The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. by Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG.; 2002 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150949

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

A case of lichenoid purpura possibly caused by diltiazem hydrochloride. Author(s): Inui S, Itami S, Yoshikawa K. Source: The Journal of Dermatology. 2001 February; 28(2): 100-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320702

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A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Author(s): Mahgoub AA, El-Medany AH, Abdulatif AS. Source: Saudi Med J. 2002 June; 23(6): 725-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12070557

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A comparison of esmolol & diltiazem for heart rate control during coronary revascularisation on beating heart. Author(s): Chauhan S, Saxena N, Rao BH, Singh RS, Bhan A. Source: The Indian Journal of Medical Research. 1999 November; 110: 174-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10680303

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

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A possible suicide by diltiazem overdose. Author(s): Kalin JR, Wood KM, Lee AJ. Source: Journal of Analytical Toxicology. 1994 May-June; 18(3): 180-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8065130

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A preliminary report of diltiazem and ketoconazole. Their cyclosporine-sparing effect and impact on transplant outcome. Author(s): Patton PR, Brunson ME, Pfaff WW, Howard RJ, Peterson JC, Ramos EL, Karlix JL. Source: Transplantation. 1994 March 27; 57(6): 889-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8154037

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A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure. Author(s): Bielecki K, Kolodziejczak M. Source: Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland. 2003 May; 5(3): 256-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780888

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A randomized trial of oral vs. topical diltiazem for chronic anal fissures. Author(s): Jonas M, Neal KR, Abercrombie JF, Scholefield JH. Source: Diseases of the Colon and Rectum. 2001 August; 44(8): 1074-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11535842

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A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina. Author(s): Chugh SK, Digpal K, Hutchinson T, McDonald CJ, Miller AJ, Lahiri A. Source: Journal of Cardiovascular Pharmacology. 2001 September; 38(3): 356-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486240

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A simple and sensitive high-performance liquid chromatography assay of diltiazem and main metabolites in renal transplanted patients. Author(s): Christensen H, Carlson E, Asberg A, Schram L, Berg KJ. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1999 May; 283(1-2): 63-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10404732

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Absence of a dose-response of cyclosporine levels to clinically used doses of diltiazem and verapamil. Author(s): Jacob LP, Malhotra D, Chan L, Shapiro JI. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1999 February; 33(2): 301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10023642

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Acute generalized exanthematous pustulosis induced by diltiazem: value of patch testing. Author(s): Jan V, Machet L, Gironet N, Martin L, Machet MC, Lorette G, Vaillant L. Source: Dermatology (Basel, Switzerland). 1998; 197(3): 274-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9867362

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Acute ventricular rate control in atrial fibrillation: IV combination of diltiazem and digoxin vs. IV diltiazem alone. Author(s): Wattanasuwan N, Khan IA, Mehta NJ, Arora P, Singh N, Vasavada BC, Sacchi TJ. Source: Chest. 2001 February; 119(2): 502-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11171729

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Adsorptive stripping voltammetric determination of antihypertensive agent: diltiazem. Author(s): Ghandour MA, Aboul Kasim E, Ali AM, El-Haty MT, Ahmed MM. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 June; 25(3-4): 443-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377024

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Ambulatory blood pressure profiles in patients treated with once-daily diltiazem extended-release or indapamide alone or in combination. Author(s): Prisant LM; Dilacor XR/Lozol Study Group. Source: American Journal of Therapeutics. 2000 May; 7(3): 177-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317166

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Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Author(s): Delle Karth G, Geppert A, Neunteufl T, Priglinger U, Haumer M, Gschwandtner M, Siostrzonek P, Heinz G. Source: Critical Care Medicine. 2001 June; 29(6): 1149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11395591

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Amlodipine versus diltiazem CR in the reduction of the total ischemic burden: the Circadian Anti-Ischemia Program in Europe (CAPE) II trial--clinical rationale and methodology. Author(s): Deanfield JE. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1998 October; 12 Suppl 3: 239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9800053

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An extremely severe case of cutaneous calcinosis with juvenile dermatomyositis, and successful treatment with diltiazem. Author(s): Ichiki Y, Akiyama T, Shimozawa N, Suzuki Y, Kondo N, Kitajima Y. Source: The British Journal of Dermatology. 2001 April; 144(4): 894-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298557

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Anomalies in the dosing of diltiazem. Author(s): Pool PE. Source: Clin Cardiol. 2000 January; 23(1): 18-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10680025

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Antihypertensive efficacy and tolerability of once-daily sustained-release diltiazem alone and in combination with ramipril in hypertension. Author(s): Tuteja R, Swarup D, Saxena GN, Bhandari S, Sharma P. Source: J Assoc Physicians India. 1999 October; 47(10): 962-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10778687

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Baroreceptor reflex to neck suction and its modification by diltiazem in man. Author(s): Kawashima S, Kogame T, Tateishi J, Iwasaki T. Source: Japanese Heart Journal. 1989 May; 30(3): 343-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2795872

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Beneficial effect of diltiazem, a new antianginal drug, on angina pectoris at rest. Author(s): Nakamura M, Koiwaya Y. Source: Japanese Heart Journal. 1979 September; 20(5): 613-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=501927

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Beneficial effect of intravenous diltiazem in the acute management of paroxysmal supraventricular tachyarrhythmias. Author(s): Betriu A, Chaitman BR, Bourassa MG, Brevers G, Scholl JM, Bruneau P, Gagne P, Chabot M. Source: Circulation. 1983 January; 67(1): 88-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6847809

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Beneficial effects of diltiazem and propranolol, alone and in combination, in patients with stable angina pectoris. Author(s): Kenny J, Kiff P, Holmes J, Jewitt DE. Source: British Heart Journal. 1985 January; 53(1): 43-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3881104

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Beneficial effects of diltiazem combined with beta blockade in angina pectoris. Author(s): Kenny J, Daly K, Bergman G, Kerkez S, Jewitt DE. Source: European Heart Journal. 1985 May; 6(5): 418-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2864247

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Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction. Author(s): Pizzetti G, Mailhac A, Li Volsi L, Di Marco F, Lu C, Margonato A, Chierchia SL. Source: Ital Heart J. 2001 October; 2(10): 757-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721720

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Beneficial effects of diltiazem in coronary artery disease. Author(s): Kenny J, Daly K, Bergman G, Kerkez S, Jewitt DE. Source: British Heart Journal. 1984 July; 52(1): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6743423

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Beneficial effects of high-dose diltiazem in patients with persistent effort angina on beta-blockers and nitrates: a randomized, double-blind, placebo-controlled cross-over study. Author(s): Boden WE, Bough EW, Reichman MJ, Rich VB, Young PM, Korr KS, Shulman RS. Source: Circulation. 1985 June; 71(6): 1197-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2859931

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Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy. Author(s): Figulla HR, Rechenberg JV, Wiegand V, Soballa R, Kreuzer H. Source: Journal of the American College of Cardiology. 1989 March 1; 13(3): 653-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2918172

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Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure. Author(s): Walsh RW, Porter CB, Starling MR, O'Rourke RA. Source: Journal of the American College of Cardiology. 1984 April; 3(4): 1044-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6707341

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Bepridil treatment of chronic stable angina: a review of comparative studies versus placebo, nifedipine, and diltiazem. Author(s): DiBianco R. Source: The American Journal of Cardiology. 1992 April 9; 69(11): 56D-62D. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1532468

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Binding of diltiazem to albumin, alpha 1-acid glycoprotein and to serum in man. Author(s): Belpaire FM, Bogaert MG. Source: Journal of Clinical Pharmacology. 1990 April; 30(4): 311-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2341578

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Bioavailability of diltiazem as a function of the administered dose. Author(s): Bianchetti G, Regazzi M, Rondanelli R, Ascalone V, Morselli PL. Source: Biopharmaceutics & Drug Disposition. 1991 July; 12(5): 391-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1878535

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Bioequivalence and relative bioavailability of a new diltiazem sustained release formulation. Author(s): Scheiwe MW, Lankhaar G, Kleinbloesem CH. Source: Arzneimittel-Forschung. 1996 October; 46(10): 960-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8931888

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Bioequivalence assessment of diltiazem preparations by means of discriminant analysis of data from solid-phase extraction and liquid chromatography. Author(s): Chaves das Neves HJ, Gomes da Silva MD, Rocha MP. Source: Journal of Pharmaceutical and Biomedical Analysis. 1991; 9(10-12): 941-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1822216

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Bioequivalence assessment of two different tablet formulations of diltiazem after single and repeated doses in healthy subjects. Author(s): Loffreda A, Matera MG, Vacca C, Motola G, De Santis D, Ruggiero A, Russo F, Fici F, Cantoni V, Lampa E, Rossi F. Source: Current Medical Research and Opinion. 1999; 15(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10216812

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Bioequivalence of two pharmaceutical forms of diltiazem. Author(s): Rubio M, Masana MI, Garcilazo E, de los Santos AR, di Girolamo G. Source: Biopharmaceutics & Drug Disposition. 1990 January-February; 11(1): 77-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2322638

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Bioinequivalence of marketed diltiazem preparations. Author(s): Joshi MV, Gokhale PC, Pohujani SM, Dalvi SS, Karandikar SM, Kshirsagar NA. Source: European Journal of Clinical Pharmacology. 1990; 39(2): 189-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2253673

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Blood pressure control with diltiazem XR, a novel extended-release formulation of diltiazem HCl, in mature and elderly hypertensive patients. Author(s): Fiddes R, Heym H, Hilty W, Lewin AJ, Codispoti J, McNally C, Stokes A, Gilderman L. Source: Clinical Therapeutics. 1994 March-April; 16(2): 209-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8062317

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Calcifying lupus panniculitis in a patient with subacute cutaneous lupus erythematosus: response to diltiazem and chloroquine. Author(s): Morgan KW, Callen JP. Source: The Journal of Rheumatology. 2001 September; 28(9): 2129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11550987

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Calcium channel blockers verapamil and diltiazem impaired rubratoxin B-caused toxicity in HL60 cells. Author(s): Nagashima H, Goto T. Source: Toxicology Letters. 2000 December 20; 118(1-2): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11137308

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Characterization of drug release from diltiazem-loaded polylactide microspheres prepared using sodium caseinate and whey protein as emulsifying agents. Author(s): Corrigan OI, Heelan BA. Source: Journal of Microencapsulation. 2001 May-June; 18(3): 335-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11308224

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Clinical outcomes of aneurysmal subarachnoid hemorrhage patients treated with oral diltiazem and limited intensive care management. Author(s): Papavasiliou AK, Harbaugh KS, Birkmeyer NJ, Feeney JM, Martin PB, Faccio C, Harbaugh RE. Source: Surgical Neurology. 2001 March; 55(3): 138-46; Discussion 146-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11311906

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Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers. Author(s): Christensen H, Asberg A, Holmboe AB, Berg KJ. Source: European Journal of Clinical Pharmacology. 2002 November; 58(8): 515-20. Epub 2002 October 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451428

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Combined administration of diltiazem and nicardipine attenuates hypertensive responses to emergence and extubation. Author(s): Tsutsui T. Source: Journal of Neurosurgical Anesthesiology. 2002 April; 14(2): 89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907387

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Combined diltiazem and lidocaine reduces cardiovascular responses to tracheal extubation and anesthesia emergence in hypertensive patients. Author(s): Fujii Y, Saitoh Y, Takahashi S, Toyooka H. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 October; 46(10): 952-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10522582

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Comparative bioavailability of diltiazem in prolonged-release oral preparations. Author(s): Quiroga PA, Yuln GV, Palummo M, Cingolani A, Dall LL, Volonte MG. Source: Drug Development and Industrial Pharmacy. 2001 November; 27(10): 1099-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11794812

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Comparative study of the use of diltiazem as an antispasmodic drug in coronary angiography via the transradial approach. Author(s): Mont'Alverne Filho JR, Assad JA, Zago Ado C, da Costa RL, Pierre AG, Saleh MH, Barretto R, Braga SL, Feres F, Sousa AG, Sousa JE. Source: Arquivos Brasileiros De Cardiologia. 2003 July; 81(1): 59-63, 54-8. Epub 2003 July 31. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12908073

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Comparison of clinical efficacy and adverse effects between extended-release felodipine and slow-release diltiazem in patients with isolated systolic hypertension. Author(s): Chern MS, Lin FC, Wu D. Source: Changgeng Yi Xue Za Zhi. 1999 March; 22(1): 44-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10418209

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Comparison of efficacy of intravenous diltiazem and esmolol in terminating supraventricular tachycardia. Author(s): Gupta A, Naik A, Vora A, Lokhandwala Y. Source: J Assoc Physicians India. 1999 October; 47(10): 969-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10778689

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Comparison of home and office blood pressure in treated hypertensives in the Nordic Diltiazem (NORDIL) Study. Author(s): Kjeldsen SE, Hedner T, Syvertsen JO, Lund-Johansen P, Hansson L; NORDIL Group. Nordic Diltiazem. Source: Blood Pressure. 2002; 11(6): 371-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12523681

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Comparison of intravenous metoprolol, verapamil and diltiazem on the attenuation of haemodynamic changes associated with tracheal extubation. Author(s): Yorukoglu D, Goktug A, Alanoglu Z, Tulunay M. Source: European Journal of Anaesthesiology. 1999 July; 16(7): 462-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10457878

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Comparison of response to serotonin of radial artery grafts and internal mammary grafts to native coronary arteries and the effect of diltiazem. Author(s): Sperti G, Manasse E, Kol A, Canosa C, Grego S, Milici C, Schiavello R, Possati GF, Crea F, Maseri A. Source: The American Journal of Cardiology. 1999 February 15; 83(4): 592-6, A8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10073868

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Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem. Author(s): Smith DH, Neutel JM, Weber MA. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1999 October; 12(1O Pt 1): 1030-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10560790

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Continuous intravenous diltiazem infusion for short-term ventricular rate control in children. Author(s): Pass RH, Liberman L, Al-Fayaddh M, Flynn P, Hordof AJ. Source: The American Journal of Cardiology. 2000 September 1; 86(5): 559-62, A9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11009280

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Control of systemic hypertension with diltiazem, a calcium-antagonist, in patients with a mildly elevated intracranial pressure: a comparative study. Author(s): Hirayama T, Katayama Y, Kano T, Tsubokawa T. Source: Neurological Research. 1994 April; 16(2): 97-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7914008

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Cost analysis of diltiazem and nitroglycerin for the prevention of coronary bypass conduit spasm. Author(s): Reddy P, White CM, Song J. Source: The Annals of Thoracic Surgery. 2001 November; 72(5): 1798-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11722109

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Cyclosporine-induced encephalopathy predisposed by diltiazem in a patient with aplastic anemia. Author(s): Jiang TT, Huang W, Patel D. Source: The Annals of Pharmacotherapy. 1999 June; 33(6): 750-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10410193

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CYP2D6 is involved in O-demethylation of diltiazem. An in vitro study with transfected human liver cells. Author(s): Molden E, Asberg A, Christensen H. Source: European Journal of Clinical Pharmacology. 2000 November; 56(8): 575-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11151747

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Desacetyl-diltiazem displays severalfold higher affinity to CYP2D6 compared with CYP3A4. Author(s): Molden E, Asberg A, Christensen H. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2002 January; 30(1): 1-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744603

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Development and characterization of transdermal drug delivery systems for diltiazem hydrochloride. Author(s): Jain SK, Chourasia MK, Sabitha M, Jain R, Jain AK, Ashawat M, Jha AK. Source: Drug Delivery. 2003 July-September; 10(3): 169-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944137

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Development and validation of a non-linear IVIVC model for a diltiazem extended release formulation. Author(s): Sirisuth N, Augsburger LL, Eddington ND. Source: Biopharmaceutics & Drug Disposition. 2002 January; 23(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11891668

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Diltiazem affects human dendritic cell maturation. Author(s): Bachetoni A, D'Ambrosio A, Mariani P, Cortesini R, Quintieri F. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 231-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11266794

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Diltiazem co-treatment in renal transplant patients receiving microemulsion cyclosporin. Author(s): Kumana CR, Tong MK, Li CS, Lauder IJ, Lee JS, Kou M, Walley T, Haycox A, Chan TM. Source: British Journal of Clinical Pharmacology. 2003 December; 56(6): 670-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616428

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Diltiazem downregulates IL-12 production by human dendritic cells. Author(s): D'Ambrosio A, Bachetoni A, Giacomini E, Quaranta M, Quintieri F. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 236-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11266797

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Diltiazem for nocturnal leg cramps. Author(s): Voon WC, Sheu SH. Source: Age and Ageing. 2001 January; 30(1): 91-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11322688

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Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a prospective study. Author(s): Jonas M, Speake W, Scholefield JH. Source: Diseases of the Colon and Rectum. 2002 August; 45(8): 1091-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195195

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Diltiazem impairs maturation and functions of human dendritic cells. Author(s): Bachetoni A, D'Ambrosio A, Mariani P, Cortesini R, Quintieri F. Source: Human Immunology. 2002 July; 63(7): 524-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072188

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Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction. Author(s): Bergman AS, Odar-Cederlof I, Westman L, Bjellerup P, Hoglund P, Ohqvist G. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2002 June; 16(3): 294-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12073199

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Diltiazem may preserve renal tubular integrity after cardiac surgery. Author(s): Piper SN, Kumle B, Maleck WH, Kiessling AH, Lehmann A, Rohm KD, Suttner SW, Boldt J. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 March; 50(3): 285-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620953

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Diltiazem provides higher internal mammary artery flow than nitroglycerin during coronary artery bypass grafting surgery. Author(s): Tabel Y, Hepaguslar H, Erdal C, Catalyurek H, Acikel U, Elar Z, Aslan O. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2004 April; 25(4): 553-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037271

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Diltiazem treatment does not alter renal function after thoracic surgery. Author(s): Amar D, Fleisher M. Source: Chest. 2001 May; 119(5): 1476-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11348956

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Diltiazem versus nitroglycerin for myocardial protection following coronary artery bypass grafting as assessed by dobutamine stress echocardiography. Author(s): Lassnigg A, Wutte M, Grubhofer G, Chevtchik O, Podesser B, Simon-Kupilik N, Wild T, Hiesmayr M, Seitelberger R. Source: Wiener Klinische Wochenschrift. 2001 June 15; 113(11-12): 439-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467090

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Diltiazem-induced hyperpigmentation in an African American woman. Author(s): Chawla A, Goyal S. Source: Journal of the American Academy of Dermatology. 2002 March; 46(3): 468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11862194

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Diltiazem-induced myoclonus. Author(s): Jeret JS. Source: Neurology. 2002 September 24; 59(6): 962; Author Reply 962. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12297601

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Diltiazem-induced photodistributed hyperpigmentation. Author(s): Boyer M, Katta R, Markus R. Source: Dermatology Online Journal [electronic Resource]. 2003 December; 9(5): 10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996383

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Diltiazem-mediated inhibition of sildenafil metabolism may promote nitrate-induced hypotension. Author(s): Howes L. Source: Internal Medicine Journal. 2001 August; 31(6): 373; Author Reply 374-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11529595

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Does diltiazem inhibit the inflammatory response in cardiopulmonary bypass? Author(s): Fansa I, Gol M, Nisanoglu V, Yavas S, Iscan Z, Tasdemir O. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 April; 9(4): Pi30-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709682

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Effect of amiodarone +/- diltiazem +/- beta blocker on frequency of atrial fibrillation, length of hospitalization, and hospital costs after coronary artery bypass grafting. Author(s): Kim MH, Rachwal W, McHale C, Bruckman D, Decena BF, Russman P, Morady F, Eagle KA. Source: The American Journal of Cardiology. 2002 May 1; 89(9): 1126-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988208

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Effect of combined dopamine and diltiazem on renal function after cardiac surgery. Author(s): Yavuz S, Ayabakan N, Goncu MT, Ozdemir IA. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 May; 8(5): Pi45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011785

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Effect of concomitant colestipol hydrochloride administration on the bioavailability of diltiazem from immediate- and sustained-release formulations. Author(s): Turner SW, Jungbluth GL, Knuth DW. Source: Biopharmaceutics & Drug Disposition. 2002 December; 23(9): 369-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12469330

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Effect of continuous low-dose intravenous diltiazem on epidural fentanyl analgesia after lower abdominal surgery. Author(s): Nitahara K, Matsunaga M, Katori K, Yotsui H, Higuchi H, Higa K. Source: British Journal of Anaesthesia. 2003 April; 90(4): 507-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644426

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Effect of diltiazem and methylene blue on human sperm motility, viability and cervical mucus penetration: potential use as vas irrigants at the time of vasectomy. Author(s): Wood BL, Doncel GF, Reddy PR, Sokal DC. Source: Contraception. 2003 March; 67(3): 241-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618261

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Effect of diltiazem on cardiac function assessed by echocardiography and neurohumoral factors after reperfused myocardial infarction without congestive heart failure. Author(s): Maki N, Yoshiyama M, Omura T, Yoshimura T, Kawarabayashi T, Sakamoto K, Hirota K, Iida H, Takeuchi K, Yoshikawa J. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001 November; 15(6): 493-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916358

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Effect of diltiazem on the recurrence rate of paroxysmal atrial fibrillation. Author(s): Tse HF, Lau CP, Wang Q, Pelosi F, Oral H, Knight BP, Strickberger SA, Morady F. Source: The American Journal of Cardiology. 2001 September 1; 88(5): 568-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11524073

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Effects of amiodarone and diltiazem on persistent atrial fibrillation conversion and recurrence rates: a randomized controlled study. Author(s): Manios EG, Mavrakis HE, Kanoupakis EM, Kallergis EM, Dermitzaki DN, Kambouraki DC, Vardas PE. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2003 January; 17(1): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843685

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Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease. Author(s): Serro-Azul JB, de Paula RS, Gruppi C, Pinto L, Pierri H, Nussbacher A, Gebara O, Moffa P, Pereira-Barreto AC, Wajngarten M. Source: Arquivos Brasileiros De Cardiologia. 2001 April; 76(4): 268-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323730

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Effects of CYP3A4 inhibition by diltiazem on pharmacokinetics and dynamics of diazepam in relation to CYP2C19 genotype status. Author(s): Kosuge K, Jun Y, Watanabe H, Kimura M, Nishimoto M, Ishizaki T, Ohashi K. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 October; 29(10): 1284-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11560871

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Effects of diltiazem and esmolol on cycle length and spontaneous conversion of atrial fibrillation. Author(s): Sticherling C, Tada H, Hsu W, Bares AC, Oral H, Pelosi F, Knight BP, Strickberger SA, Morady F. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2002 April; 7(2): 818. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12075396

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Effects of diltiazem on down-regulation of lymphocyte beta-adrenoceptors in patients with chronic congestive heart failure. Author(s): Zhang XL, Xu B, Feng Y. Source: Acta Pharmacologica Sinica. 2000 October; 21(10): 927-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501046

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Effects of diltiazem on human nicotinic acetylcholine and GABA(A) receptors. Author(s): Houlihan LM, Slater EY, Beadle DJ, Lukas RJ, Bermudez I. Source: Neuropharmacology. 2000 October; 39(13): 2533-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11044725

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Effects of diltiazem on platelet activation and cytosolic calcium during percutaneous transluminal coronary angioplasty. Author(s): Dai H, Chen J, Tao Q, Zhu J, Zhang F, Zheng L, Qiu Y. Source: Postgraduate Medical Journal. 2003 September; 79(935): 522-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679549

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Effects of diltiazem prophylaxis on the incidence and clinical outcome of atrial arrhythmias after thoracic surgery. Author(s): Amar D, Roistacher N, Rusch VW, Leung DH, Ginsburg I, Zhang H, Bains MS, Downey RJ, Korst RJ, Ginsberg RJ. Source: The Journal of Thoracic and Cardiovascular Surgery. 2000 October; 120(4): 790-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11003764

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Effects of nicardipine and diltiazem on the bispectral index and 95% spectral edge frequency. Author(s): Hirota K, Kabara S, Kushikata T, Kitayama M, Ishihara H, Matsuki A. Source: European Journal of Anaesthesiology. 2003 October; 20(10): 809-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580050

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Effects of preoperative treatment with diltiazem on diastolic ventricular function after coronary artery bypass graft surgery. Author(s): van der Maaten JM, de Vries AJ, Henning RH, Epema AH, van den Berg MP, Lip H. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2001 December; 15(6): 710-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748518

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Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. Author(s): Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA; Combination Assessment of Ranolazine In Stable Angina (CARISA) Investigators. Source: Jama : the Journal of the American Medical Association. 2004 January 21; 291(3): 309-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734593

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Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension. Author(s): Glasser SP, Neutel JM, Gana TJ, Albert KS. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 January; 16(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517683

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Esmolol versus diltiazem in atrial fibrillation following coronary artery bypass graft surgery. Author(s): Hilleman DE, Reyes AP, Mooss AN, Packard KA. Source: Current Medical Research and Opinion. 2003; 19(5): 376-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678474

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Failure of diltiazem to prevent restenosis after percutaneous transluminal coronary angioplasty. Author(s): Corcos T, David PR, Val PG, Renkin J, Dangoisse V, Rapold HG, Bourassa MG. Source: American Heart Journal. 1985 May; 109(5 Pt 1): 926-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3158187

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Fatal diltiazem overdose: report of four cases and review of the literature. Author(s): Roper TA, Sykes R, Gray C. Source: Postgraduate Medical Journal. 1993 June; 69(812): 474-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8208646

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Fatal renal and hepatic toxicity after treatment with diltiazem. Author(s): Shallcross H, Padley SP, Glynn MJ, Gibbs DD. Source: British Medical Journal (Clinical Research Ed.). 1987 November 14; 295(6608): 1236-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3120959

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Fatality due to intravenous diltiazem for acute ventricular rate control. Author(s): Moser LR, Panacek EA, Munger MA. Source: Pharmacotherapy. 1996 March-April; 16(2): 306-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8820477

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Favourable long term prognosis in patients with non-Q wave acute myocardial infarction not associated with specific electrocardiographic changes. Diltiazem Reinfarction Study Research Group. Author(s): Boden WE, Kleiger RE, Gibson RS, Reddy BR, Schechtman KB, Schwartz DJ, Capone RJ, Roberts R. Source: British Heart Journal. 1989 May; 61(5): 396-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2660893

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First-pass metabolism of cyclosporine A in human intestine: inhibition by diltiazem. Author(s): Preuner JG, Lehle K, Eichinger H, Rupprecht L. Source: Transplantation Proceedings. 1998 September; 30(6): 2545-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9745480

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Formulation and in vitro evaluation of polymeric films of diltiazem hydrochloride and indomethacin for transdermal administration. Author(s): Rao PR, Diwan PV. Source: Drug Development and Industrial Pharmacy. 1998 April; 24(4): 327-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876592

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Formulation of diltiazem affects cyclosporin-sparing activity. Author(s): Jones TE, Morris RG, Mathew TH. Source: European Journal of Clinical Pharmacology. 1997; 52(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9143868

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Frequency and significance of late evolution of Q waves in patients with initial nonQ-wave acute myocardial infarction. Diltiazem Reinfarction Study Group. Author(s): Kleiger RE, Boden WE, Schechtman KB, Gibson RS, Schwartz DJ, Geiger BJ, Capone RJ, Roberts R. Source: The American Journal of Cardiology. 1990 January 1; 65(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2403730

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Further elucidation of pharmacokinetic interaction between diltiazem and warfarin. Author(s): Stoysich AM, Lucas BD, Mohiuddin SM, Hilleman DE. Source: Int J Clin Pharmacol Ther. 1996 February; 34(2): 56-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8929747

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Gallopamil and diltiazem: a double-blind, randomized, cross-over trial in effort ischaemia. Author(s): Marraccini P, Orsini E, Brunelli C, Nassi G, Ghigliotti G, Iannetti M, Caponnetto S, L'Abbate A. Source: European Heart Journal. 1992 March; 13(3): 404-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1597229

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Gender differences in exercise and recovery blood pressure responses in normal volunteers given diltiazem. Author(s): Klassen GA, Yeung PF, Barclay KD, Hung OR, Pollak PT, Buckley SJ. Source: Journal of Clinical Pharmacology. 1995 December; 35(12): 1144-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8750364

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Gender related pharmacokinetics of diltiazem in healthy subjects. Author(s): Saenz-Campos D, Bayes MC, Martin S, Barbanoj MJ, Jane F. Source: Int J Clin Pharmacol Ther. 1995 July; 33(7): 397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7582396

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Generalized cutaneous reaction to diltiazem. Author(s): Sousa-Basto A, Azenha A, Duarte ML, Pardal-Oliveira F. Source: Contact Dermatitis. 1993 July; 29(1): 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8365158

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Gingival hyperplasia: a side effect of nifedipine and diltiazem. Author(s): Fattore L, Stablein M, Bredfeldt G, Semla T, Moran M, Doherty-Greenberg JM. Source: Spec Care Dentist. 1991 May-June; 11(3): 107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1887359

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Gingival overgrowth induced by diltiazem. A case report. Author(s): Bowman JM, Levy BA, Grubb RV. Source: Oral Surg Oral Med Oral Pathol. 1988 February; 65(2): 183-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3422722

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Glycoregulation is not altered by short-term administration of diltiazem in nondiabetic humans. Author(s): Zofkova I, Stolba P, Husek P. Source: Exp Clin Endocrinol. 1992; 100(3): 120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1305062

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Guar gum-based sustained release diltiazem. Author(s): Altaf SA, Yu K, Parasrampuria J, Friend DR. Source: Pharmaceutical Research. 1998 August; 15(8): 1196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9706049

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Haemodynamic effects of diltiazem at rest and during exercise in patients with previous myocardial infarction. Author(s): Cobelli F, Opasich C, Riccardi G, Rossetti S, Guffanti E, Specchia G. Source: European Heart Journal. 1987 July; 8(7): 710-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3653122

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Health outcomes associated with beta-blocker and diltiazem treatment of unstable angina. Author(s): Smith NL, Reiber GE, Psaty BM, Heckbert SR, Siscovick DS, Ritchie JL, Every NR, Koepsell TD. Source: Journal of the American College of Cardiology. 1998 November; 32(5): 1305-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9809940

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Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem. Author(s): Boden WE, Vray M, Eschwege E, Lauret D, Scheldewaert R. Source: Clin Cardiol. 2001 January; 24(1): 73-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195610

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Hematologic complications of diltiazem overdose. Author(s): Fang CC, Tsai LM. Source: American Heart Journal. 1993 October; 126(4): 1017-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8213426

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Hemodynamic and echocardiographic assessment of the effects of diltiazem during transient occlusion of the left anterior descending coronary artery during percutaneous transluminal coronary angioplasty. Author(s): Kern MJ, Pearson A, Woodruff R, Deligonul U, Vandormael M, Labovitz A. Source: The American Journal of Cardiology. 1989 October 15; 64(14): 849-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2679030

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Hemodynamic and metabolic effects of diltiazem during coronary sinus pacing with particular reference to left ventricular ejection fraction. Author(s): Josephson MA, Hopkins J, Singh BN. Source: The American Journal of Cardiology. 1985 February 1; 55(4): 286-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3969863

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Hemodynamic effects of intravenous diltiazem in hypoxic pulmonary hypertension. Author(s): Clozel JP, Delorme N, Battistella P, Breda JL, Polu JM. Source: Chest. 1987 February; 91(2): 171-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3802928

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Hemodynamic effects of intravenous diltiazem in patients treated chronically with propranolol. Author(s): Rocha P, Baron B, Delestrain A, Pathe M, Cazor JL, Kahn JC. Source: American Heart Journal. 1986 January; 111(1): 62-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3946161

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Hemodynamic tolerability and anti-ischemic efficacy of high dose intravenous diltiazem in patients with normal versus impaired ventricular function. Author(s): Remme WJ, Krauss XH, van Hoogenhuyze DC, Kruyssen DA. Source: Journal of the American College of Cardiology. 1993 March 1; 21(3): 709-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8436753

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Heterogeneous interference of nicardipine, verapamil, and diltiazem with forearm arteriolar responsiveness to adrenergic stimulation in hypertensive patients. Author(s): Pedrinelli R, Salvetti A. Source: American Heart Journal. 1991 July; 122(1 Pt 2): 342-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2053555

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High-performance liquid chromatographic assay of diltiazem and six of its metabolites in plasma: application to a pharmacokinetic study in healthy volunteers. Author(s): Yeung PK, Montague TJ, Tsui B, McGregor C. Source: Journal of Pharmaceutical Sciences. 1989 July; 78(7): 592-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2778663

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High-performance liquid chromatographic determination of diltiazem and four of its metabolites in plasma. Application to pharmacokinetics. Author(s): Goebel KJ, Kolle EU. Source: Journal of Chromatography. 1985 December 13; 345(2): 355-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4086603

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High-performance liquid chromatographic determination of diltiazem and four of its metabolites in plasma: evaluation of their stability. Author(s): Dube LM, Mousseau N, McGilveray IJ. Source: Journal of Chromatography. 1988 August 19; 430(1): 103-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3215945

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High-performance liquid chromatographic determination of diltiazem and its major metabolites, N-monodemethyldiltiazem and desacetyldiltiazem, in plasma. Author(s): Montamat SC, Abernethy DR, Mitchell JR. Source: Journal of Chromatography. 1987 March 20; 415(1): 203-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3584358

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High-performance liquid chromatographic determination of diltiazem and two of its metabolites in plasma using a short alkyl chain silanol deactivated column. Author(s): Rutledge DR, Abadi AH, Lopez LM, Beaudreau CA. Source: Journal of Chromatography. 1993 May 19; 615(1): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8340449

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High-performance liquid chromatographic determination of diltiazem in human plasma after solid-phase and liquid-liquid extraction. Author(s): Zendelovska D, Stafilov T, Stefova M. Source: Analytical and Bioanalytical Chemistry. 2003 July; 376(6): 848-53. Epub 2003 June 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811463

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High-performance liquid chromatographic method for the determination of diltiazem and two of its metabolites in human plasma: application to a new sustained release formulation. Author(s): Boucher S, Varin F, Theoret Y, Du Souich P, Caille G. Source: Journal of Pharmaceutical and Biomedical Analysis. 1989; 7(12): 1925-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2490585

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High-performance liquid chromatography-mass spectrometry analysis of diltiazem and 11 of its phase I metabolites in human plasma. Author(s): Molden E, Helen Boe G, Christensen H, Reubsaet L. Source: Journal of Pharmaceutical and Biomedical Analysis. 2003 September 19; 33(2): 275-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972092

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HPLC measurement of diltiazem and desacetyldiltiazem in serum or plasma. Author(s): Bhamra RK, Ward AE, Holt DW. Source: Biomedical Chromatography : Bmc. 1987; 2(4): 180-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3507233

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Impact of diltiazem administration and cyclosporine levels on the incidence of acute rejection in heart transplant patients. Author(s): Delgado JF, Sanchez V, de la Calzada CS, Gomez-Sanchez MA, Escribano P, Cea-Calvo L, Pascual JG, de la Camara AG, Sotelo T, Rufilanchas JJ. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2003 September; 16(9): 676-80. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783159

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Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect. Author(s): Basu SK, Kinsey CD, Miller AJ, Lahiri A. Source: American Journal of Therapeutics. 2000 January; 7(1): 17-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11319569

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Incidence of cancer in postmyocardial infarction patients treated with short-acting nifedipine and diltiazem. Secondary Prevention Group. Author(s): Kanamasa K, Kimura A, Miyataka M, Takenaka T, Ishikawa K. Source: Cancer. 1999 March 15; 85(6): 1369-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10189144

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Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study. Author(s): Kjeldsen SE, Hedner T, Syvertsen JO, Lund-Johansen P, Hansson L, Lanke J, Lindholm LH, De Faire U, Dahlof B, Karlberg BE; NORDIL Study Group. Source: Journal of Hypertension. 2002 June; 20(6): 1231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023696

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Influence of diltiazem on the pharmacokinetics of amlodipine in elderly hypertensive patients. Author(s): Sasaki M, Maeda A, Fujimura A. Source: European Journal of Clinical Pharmacology. 2001 April; 57(1): 85-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11372598

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Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomes. Author(s): Yeo KR, Yeo WW. Source: British Journal of Clinical Pharmacology. 2001 May; 51(5): 461-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422004

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INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Author(s): Kjeldsen SE, Westheim AS, Os I. Source: Lancet. 2000 December 2; 356(9245): 1929-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130406

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INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Author(s): Fournier A, Georgita A, Bouffandeau B, Oprisiu R. Source: Lancet. 2000 December 2; 356(9245): 1927; Author Reply 1928-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130405

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INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Author(s): Avanzini F, Tognoni G. Source: Lancet. 2000 December 2; 356(9245): 1927-8; Author Reply 1928-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130404

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INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Author(s): Bertram M. Source: Lancet. 2000 December 2; 356(9245): 1926; Author Reply 1928-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130403

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INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Author(s): Garcia-Lopez FJ, de Alvaro F. Source: Lancet. 2000 December 2; 356(9245): 1926; Author Reply 1928-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130402

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INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study. Author(s): Achard JM, Oudart N, Aldigier JC. Source: Lancet. 2000 December 2; 356(9245): 1926-7; Author Reply 1928-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11130401

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Interaction between timolol eyedrops and oral nicardipine or oral diltiazem in healthy Japanese subjects. Author(s): Yatsuka YI, Tsutsumi K, Kotegawa T, Nakamura K, Nakano S, Nakatsuka K. Source: European Journal of Clinical Pharmacology. 1998 April; 54(2): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9626919

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Interventional study of diltiazem in dilated cardiomyopathy: a report of multiple centre clinical trial in China. Chinese Cooperative Group of Diltiazem Intervention Trial in Dilated Cardiomyopathy. Author(s): Liao YH. Source: International Journal of Cardiology. 1998 March 13; 64(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579813

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Intravenous diltiazem and acute renal failure after cardiac operations. Author(s): Young EW, Diab A, Kirsh MM. Source: The Annals of Thoracic Surgery. 1998 May; 65(5): 1316-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9594859

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Intravenous diltiazem and CYP3A-mediated metabolism. Author(s): Masica AL, Azie NE, Brater DC, Hall SD, Jones DR. Source: British Journal of Clinical Pharmacology. 2000 September; 50(3): 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971313

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Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial. Author(s): Theroux P, Gregoire J, Chin C, Pelletier G, de Guise P, Juneau M. Source: Journal of the American College of Cardiology. 1998 September; 32(3): 620-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9741502

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Intravenous magnesium sulfate versus diltiazem in paroxysmal atrial fibrillation. Author(s): Chiladakis JA, Stathopoulos C, Davlouros P, Manolis AS. Source: International Journal of Cardiology. 2001 July; 79(2-3): 287-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11461753

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Is diltiazem as effective as diuretics and beta-blockers in preventing complications from hypertension? Author(s): Adelman A. Source: The Journal of Family Practice. 2000 November; 49(11): 1049. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11093573

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Is vitamin C superior to diltiazem for radial artery vasodilation in patients awaiting coronary artery bypass grafting? Author(s): Drossos GE, Toumpoulis IK, Katritsis DG, Ioannidis JP, Kontogiorgi P, Svarna E, Anagnostopoulos CE. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 February; 125(2): 3305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579102

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Kidney protective effect of diltiazem after renal transplantation with long cold ischemia time and triple-drug immunosuppression. Author(s): Tenschert W, Harfmann P, Meyer-Moldenhauer WH, Arndt R, Klosterhalfen H. Source: Transplantation Proceedings. 1991 February; 23(1 Pt 2): 1334-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1989231

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Lack of effect of a diuretic added to diltiazem. Author(s): MacGregor GA, Cappuccio FP. Source: Journal of Human Hypertension. 1997 April; 11(4): 249-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9185031

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Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Author(s): Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A. Source: Pharmazie. 1994 September; 49(9): 675-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7972311

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Lack of melatonin response to acute administration of nifedipine and diltiazem in healthy men. Author(s): Kancheva R, Zofkova I, Hill M, Kanchev L. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2000; 49 Suppl 1: S119-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984081

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L-calcium channel blockade induced by diltiazem inhibits proliferation, migration and F-actin membrane rearrangements in human vascular smooth muscle cells stimulated with insulin and IGF-1. Author(s): Ruiz-Torres A, Lozano R, Melon J, Carraro R. Source: Int J Clin Pharmacol Ther. 2003 September; 41(9): 386-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14518598

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Left ventricular myocardial perfusion and function in systemic sclerosis before and after diltiazem treatment. Author(s): Geirsson AJ, Danielsen R, Petursson E. Source: Scandinavian Journal of Rheumatology. 1996; 25(5): 317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8921925

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Lesson of the week. Unrecognised accidental overdose with diltiazem. Author(s): Satchithananda DK, Stone DL, Chauhan A, Ritchie AJ. Source: Bmj (Clinical Research Ed.). 2000 July 15; 321(7254): 160-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894696

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Lethal diltiazem poisoning. Author(s): Romano G, Barbera N, Rossitto C, Spadaro G. Source: Journal of Analytical Toxicology. 2002 September; 26(6): 374-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220021

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Life-threatening bradycardic reactions due to beta blocker-diltiazem interactions. Author(s): Yust I, Hoffman M, Aronson RJ. Source: Isr J Med Sci. 1992 May; 28(5): 292-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1350774

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Liquid chromatographic determination of celiprolol, diltiazem, desmethyldiltiazem and deacetyldiltiazem in plasma using a short alkyl chain silanol deactivated column. Author(s): Rutledge DR, Abadi AH, Lopez LM. Source: Journal of Pharmaceutical and Biomedical Analysis. 1994 January; 12(1): 135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8161601

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Lisinopril and diltiazem reduce left ventricular mass without changing blood pressure in normotensive subjects with exaggerated blood pressure response to exercise. Author(s): Polonia J, Martins L, Macedo F, Faria DB, Simoes L, Brandao F, Gomes MC. Source: Rev Port Cardiol. 1996 March; 15(3): 185-93, 179. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8634167

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Long-acting diltiazem CD is safe and effective in a hypertensive Mexican-American population. Author(s): Herrera CR, Lewin A, Fiddes R, Friedman J, Linn W, Baker T, Balanoff D, Beach CL. Source: Pharmacotherapy. 1997 November-December; 17(6): 1254-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399608

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Long-term antianginal and antiischemic effects of mibefradil, the novel T-type calcium channel blocker: a multicenter, double-blind, placebo-controlled, randomized comparison with sustained-release diltiazem. Author(s): Davies GJ, Kobrin I, Caspi A, Reisin LH, de Albuquerque DC, Armagnijan D, Coelho OR, Schneeweiss A. Source: American Heart Journal. 1997 August; 134(2 Pt 1): 220-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9313601

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Long-term effectiveness of enalapril plus extended-release diltiazem in essential hypertension. Author(s): Applegate W, Cohen JD, Wolfson P, Davis A, Green S. Source: Pharmacotherapy. 1997 January-February; 17(1): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9017770

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Long-term effects of diltiazem and atenolol on blood glucose, serum lipids, and serum urate in hypertensive patients. Swedish-Finnish Study Group. Author(s): Thulin T, Lehtonen A, Dahlof C, Nilsson-Ehle P, Engqvist L, Lagerstedt C, Berglund E. Source: Int J Clin Pharmacol Ther. 1999 January; 37(1): 28-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10027480

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Long-term effects of diltiazem and verapamil on mortality and cardiac events in nonQ-wave acute myocardial infarction without pulmonary congestion: post hoc subset analysis of the multicenter diltiazem postinfarction trial and the second danish verapamil infarction trial studies. Author(s): Gibson RS, Hansen JF, Messerli F, Schechtman KB, Boden WE. Source: The American Journal of Cardiology. 2000 August 1; 86(3): 275-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10922432

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Long-term follow-up after early intervention with intravenous diltiazem or intravenous nitroglycerin for unstable angina pectoris. Author(s): Gobel EJ, van Gilst WH, de Kam PJ, ter Napel MG, Molhoek GP, Lie KI. Source: European Heart Journal. 1998 August; 19(8): 1208-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9740342

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Long-term hemodynamic effects at rest and during exercise of newer antihypertensive agents and salt restriction in essential hypertension: review of epanolol, doxazosin, amlodipine, felodipine, diltiazem, lisinopril, dilevalol, carvedilol, and ketanserin. Author(s): Omvik P, Lund-Johansen P. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1993 April; 7(2): 193-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8395198

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Long-term prognostic significance of ST segment depression during acute myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. Author(s): Krone RJ, Greenberg H, Dwyer EM Jr, Kleiger RE, Boden WE. Source: Journal of the American College of Cardiology. 1993 August; 22(2): 361-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8335805

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Low-dose intravenous diltiazem--efficacy and safety in supraventricular tachyarrhythmias. Author(s): Seth S, Mittal A, Goel P, Wasir HS. Source: Indian Heart J. 1996 July-August; 48(4): 365-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8908822

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Lower incidence of liver graft rejection in patients on diltiazem plus cyclosporine therapy. Author(s): Mies S, Massarollo PC, Figueira ER, Leitao RM, Raia S. Source: Transplantation Proceedings. 1998 June; 30(4): 1437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636582

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Maculopapular rash induced by diltiazem: allergological investigations in four patients and cross reactions between calcium channel blockers. Author(s): Cholez C, Trechot P, Schmutz JL, Faure G, Bene MC, Barbaud A. Source: Allergy. 2003 November; 58(11): 1207-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616146

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Management of acute non-Q-wave myocardial infarction. The role of prophylactic diltiazem therapy and indications for predischarge coronary arteriography. Author(s): Gibson RS. Source: Drugs. 1991; 42 Suppl 2: 28-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1718699

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Management of non-Q-wave myocardial infarction: role of diltiazem versus betablocker therapy. Author(s): Boden WE. Source: Journal of Cardiovascular Pharmacology. 1990; 16 Suppl 6: S55-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1707117

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Massive diltiazem overdosage: clinical and pharmacokinetic observations. Author(s): Malcolm N, Callegari P, Goldberg J, Strauss H, Caille G, Vezina M, Spenard J. Source: Drug Intell Clin Pharm. 1986 November; 20(11): 888. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3780429

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Massive diltiazem overdose treated with extracorporeal membrane oxygenation. Author(s): Durward A, Guerguerian AM, Lefebvre M, Shemie SD. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 July; 4(3): 372-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12831424

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Massive diltiazem overdose. Author(s): Connolly DL, Nettleton MA, Bastow MD. Source: The American Journal of Cardiology. 1993 September 15; 72(9): 742-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8249857

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Massive diltiazem overdose. Author(s): Snover SW, Bocchino V. Source: Annals of Emergency Medicine. 1986 October; 15(10): 1221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3752656

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Medical treatment for inoperable insulinoma: clinical usefulness of diphenylhydantoin and diltiazem. Author(s): Imanaka S, Matsuda S, Ito K, Matsuoka T, Okada Y. Source: Japanese Journal of Clinical Oncology. 1986 March; 16(1): 65-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3009920

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Metabolic effects of diltiazem and atenolol: results from a randomized, double-blind study with parallel groups. Author(s): Pollare T, Lithell H, Morlin C, Prantare H, Hvarfner A, Ljunghall S. Source: Journal of Hypertension. 1989 July; 7(7): 551-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2668407

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Metabolic fate of diltiazem. Distribution, excretion and protein binding in rat and dog. Author(s): Nakamura S, Suzuki T, Sugawara Y, Usuki S, Ito Y, Kume T, Yoshikawa M, Endo H, Ohashi M, Harigaya S. Source: Arzneimittel-Forschung. 1987 November; 37(11): 1244-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3440032

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Metabolism of diltiazem. I. Structures of new acidic and basic metabolites in rat, dog and man. Author(s): Sugawara Y, Ohashi M, Nakamura S, Usuki S, Suzuki T, Ito Y, Kume T, Harigaya S, Nakao A, Gaino M, et al. Source: J Pharmacobiodyn. 1988 April; 11(4): 211-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3411439

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Metabolism of diltiazem. II. Metabolic profile in rat, dog and man. Author(s): Sugawara Y, Nakamura S, Usuki S, Ito Y, Suzuki T, Ohashi M, Harigaya S. Source: J Pharmacobiodyn. 1988 April; 11(4): 224-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3411440

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Modification of the pharmacokinetics of cyclosporine A and metabolites by the concomitant use of Neoral and diltiazem or ketoconazol in stable adult kidney transplants. Author(s): Foradori A, Mezzano S, Videla C, Pefaur J, Elberg A. Source: Transplantation Proceedings. 1998 August; 30(5): 1685-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9723244

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Modulation of ventricular rate in permanent atrial fibrillation: randomized, crossover study of the effects of slow-release formulations of gallopamil, diltiazem, or verapamil. Author(s): Botto GL, Bonini W, Broffoni T. Source: Clin Cardiol. 1998 November; 21(11): 837-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825197

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Molecular determinants of Ca2+ potentiation of diltiazem block and Ca2+-dependent inactivation in the pore region of cav1.2. Author(s): Dilmac N, Hilliard N, Hockerman GH. Source: Molecular Pharmacology. 2003 August; 64(2): 491-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869655

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Molecular determinants of diltiazem block in domains IIIS6 and IVS6 of L-type Ca(2+) channels. Author(s): Hockerman GH, Dilmac N, Scheuer T, Catterall WA. Source: Molecular Pharmacology. 2000 December; 58(6): 1264-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11093762

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Monotherapy of stable angina pectoris with bopindolol in comparison with diltiazem. Author(s): Meyer EC, Makov UE, Palant A. Source: Cardiology. 1991; 78(3): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678316

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Multicenter evaluation of the efficacy and safety of sustained-release diltiazem hydrochloride for the treatment of hypertension. Author(s): Woehler TR, Eff J, Graney W, Heald D, Ziemniak J, Magner D. Source: Clinical Therapeutics. 1992 March-April; 14(2): 148-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1611639

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Multicenter studies on the pharmacokinetic profile of sustained-release oral diltiazem (300 mg) after once a day repeated administration: influence of age. Author(s): Bianchetti G, Billy S, Ascalone V, Saivin S, Houin G, Rosenzweig P. Source: Int J Clin Pharmacol Ther. 1996 May; 34(5): 195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8738855

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Myocardial protection by intravenous diltiazem during angioplasty of single-vessel coronary artery disease. Author(s): Bonnier JJ, Huizer T, Troquay R, van Es GA, de Jong JW. Source: The American Journal of Cardiology. 1990 July 15; 66(2): 145-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2196772

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Nadolol versus diltiazem and combination for preventing exercise-induced ischemia in severe angina pectoris. Author(s): Miller WE, Vittitoe J, O'Rourke RA, Crawford MH. Source: The American Journal of Cardiology. 1988 September 1; 62(7): 372-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3414514

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Negative inotropic activity of the calcium antagonists isradipine, nifedipine, diltiazem, and verapamil in diseased human myocardium. Author(s): Schwinger RH, Bohm M, Erdmann E. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1991 February; 4(2 Pt 2): 185S-187S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1827017

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Negative inotropic properties of isradipine, nifedipine, diltiazem, and verapamil in diseased human myocardial tissue. Author(s): Schwinger RH, Bohm M, Erdmann E. Source: Journal of Cardiovascular Pharmacology. 1990 June; 15(6): 892-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1694911

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New concepts for the treatment of unstable angina: role for intravenous diltiazem. Author(s): Boden WE. Source: Journal of Cardiovascular Pharmacology. 1991; 18 Suppl 9: S1-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1725535

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Nifedipine and diltiazem but not verapamil up-regulate endothelial nitric-oxide synthase expression. Author(s): Ding Y, Vaziri ND. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 February; 292(2): 606-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10640297

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Nifedipine GITS versus diltiazem in chronic stable angina: a randomised multicentre study. Author(s): Zanolla L, Franceschini L, Rossi L, Ochan M, Amigoni S, Zardini P. Source: Br J Clin Pract Suppl. 1997 April; 88: 27-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9519505

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Nitroglycerin is preferable to diltiazem for prevention of coronary bypass conduit spasm. Author(s): Shapira OM, Alkon JD, Macron DS, Keaney JF Jr, Vita JA, Aldea GS, Shemin RJ. Source: The Annals of Thoracic Surgery. 2000 September; 70(3): 883-8; Discussion 888-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11016328

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Nitroglycerin is superior to diltiazem as a coronary bypass conduit vasodilator. Author(s): Shapira OM, Xu A, Vita JA, Aldea GS, Shah N, Shemin RJ, Keaney JF Jr. Source: The Journal of Thoracic and Cardiovascular Surgery. 1999 May; 117(5): 906-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10220683

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N-monodesmethyldiltiazem is the predominant metabolite of diltiazem in the plasma of young and elderly hypertensives. Author(s): Montamat SC, Abernethy DR. Source: British Journal of Clinical Pharmacology. 1987 August; 24(2): 185-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3620292

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No effect of clodronate on cyclosporin A blood levels in heart transplant patients simultaneously treated with diltiazem and azathioprine. Author(s): Baraldo M, Furlanut M, Puricelli C. Source: Therapeutic Drug Monitoring. 1994 August; 16(4): 435. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7974638

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No increase in serum digoxin concentration with high-dose diltiazem. Author(s): Boden WE, More G, Sharma S, Bough EW, Korr KS, Young PM, Shulman RS. Source: The American Journal of Medicine. 1986 September; 81(3): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3752143

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No significant in vitro interference of diltiazem and metabolites in digoxin radioimmunoassay (four assay methods). Author(s): Molin L, Scherling IL, Larsson H. Source: Therapeutic Drug Monitoring. 1989; 11(2): 217-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2718226

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Noncardiogenic pulmonary edema complicating massive diltiazem overdose. Author(s): Humbert VH Jr, Munn NJ, Hawkins RF. Source: Chest. 1991 January; 99(1): 258-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1984972

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Non-invasive assessment of left ventricular performance in patients with coronary artery disease after chronic diltiazem therapy. Author(s): Cinquegrana G, Spinelli L, Ferro G, Cristiano C, Spadafora M, Ferrara M. Source: Int J Clin Pharmacol Ther Toxicol. 1989 January; 27(1): 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2744903

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Noninvasive evaluation of acute effects of oral diltiazem in primary pulmonary hypertension--a preliminary study. Author(s): Misra M, Bajaj V, Kumar N, Puri VK. Source: Indian Heart J. 1986 March-April; 38(2): 114-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3557502

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Nontherapeutic cyclosporine levels. Sustained-release diltiazem products are not the same. Author(s): Cooke CE. Source: Transplantation. 1994 June 15; 57(11): 1687. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8009610

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Nonthrombocytopenic purpura associated sequentially with nifedipine and diltiazem. Author(s): Kuo M, Winiarski N, Garella S. Source: The Annals of Pharmacotherapy. 1992 September; 26(9): 1089-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1421671

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Objective evaluation of three dose levels of diltiazem in patients with chronic stable angina. Author(s): Bala Subramanian V, Khurmi NS, Bowles MJ, O'Hara M, Raftery EB. Source: Journal of the American College of Cardiology. 1983 April; 1(4): 1144-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6833654

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Once daily compared with twice daily administration of slow-release diltiazem as monotherapy for hypertension. Author(s): Nikkila M, Inkovaara J, Heikkinen J. Source: Annals of Medicine. 1991 April; 23(2): 141-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2069791

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Once-daily dosing of sustained-release diltiazem capsules in mild-to-moderate hypertension. Author(s): Ginsberg D, Pappas JE, Rofman BA, Gutgsell TL, Schumer B, Karp R, Walker SD. Source: J Am Osteopath Assoc. 1988 December; 88(12): 1489-92. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3248953

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Open comparative study to assess the efficacy and safety of two calcium antagonists, amlodipine and diltiazem, in the treatment of symptomatic myocardial ischaemia. Author(s): Caponnetto S, Canale C, Terrachini V, Masperone MA, Bruzzone F. Source: Postgraduate Medical Journal. 1991; 67 Suppl 5: S54-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1839442

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Optimization of antihypertensive therapy with a novel, extended-release formulation of diltiazem: results of a practice-based clinical study. Author(s): Neutel JM, Smith DH, Frishman WH. Source: Clinical Therapeutics. 1997 November-December; 19(6): 1379-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9444447

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Optimization of sustained-release diltiazem formulations in man by use of an invitro/in-vivo correlation. Author(s): Yu K, Gebert M, Altaf SA, Wong D, Friend DR. Source: The Journal of Pharmacy and Pharmacology. 1998 August; 50(8): 845-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9751447

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Organic psychosis caused by diltiazem. Author(s): Busche CJ. Source: Journal of the Royal Society of Medicine. 1988 May; 81(5): 296-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3385716

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Overdose of diltiazem. Author(s): Lip GY, Ferner RE. Source: Bmj (Clinical Research Ed.). 1994 July 16; 309(6948): 193. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8044106

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Overdose of diltiazem. Author(s): Roper TA. Source: Bmj (Clinical Research Ed.). 1994 June 11; 308(6943): 1571. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8019332

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Paralytic ileus induced by the combined use of nifedipine and diltiazem in the treatment of vasospastic angina. Author(s): Harada T, Ohtaki E, Sumiyoshi T, Hosoda S. Source: Cardiology. 2002; 97(2): 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978960

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Pharmacokinetic and pharmacodynamic interactions between diltiazem and methylprednisolone in healthy volunteers. Author(s): Booker BM, Magee MH, Blum RA, Lates CD, Jusko WJ. Source: Clinical Pharmacology and Therapeutics. 2002 October; 72(4): 370-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386639

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Pharmacokinetic interaction between diltiazem and tolbutamide. Author(s): Dixit AA, Rao YM. Source: Drug Metabol Drug Interact. 1999; 15(4): 269-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10716041

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Pharmacokinetic interaction between single oral doses of diltiazem and sirolimus in healthy volunteers. Author(s): Bottiger Y, Sawe J, Brattstrom C, Tollemar J, Burke JT, Hass G, Zimmerman JJ. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 32-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180036

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Pharmacokinetic interaction between tacrolimus and diltiazem: dose-response relationship in kidney and liver transplant recipients. Author(s): Jones TE, Morris RG. Source: Clinical Pharmacokinetics. 2002; 41(5): 381-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036394

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Pharmacokinetic interactions between microemulsion formulated cyclosporine A and diltiazem in renal transplant recipients. Author(s): Asberg A, Christensen H, Hartmann A, Carlson E, Molden E, Berg KJ. Source: European Journal of Clinical Pharmacology. 1999 July; 55(5): 383-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10456488

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Pharmacokinetics and hemodynamic effects of diltiazem in healthy volunteers: comparing resting with the effect of exercise. Author(s): Yeung PK, Hung OR, Pollak PT, Klassen GA. Source: Int J Clin Pharmacol Ther. 1999 August; 37(8): 413-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10475144

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Pharmacokinetics and pharmacodynamics of a slow-release formulation of diltiazem after the administration of a single and repeated doses to healthy volunteers. Author(s): Lefebvre M, Lacasse Y, Spenard J, Geadah D, Moisan R, Gossard D, Landriault H, Du Souich P, Caille G. Source: Biopharmaceutics & Drug Disposition. 1994 April; 15(3): 227-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7880983

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Pharmacokinetics of diltiazem and its metabolites in relation to CYP2D6 genotype. Author(s): Molden E, Johansen PW, Boe GH, Bergan S, Christensen H, Rugstad HE, Rootwelt H, Reubsaet L, Lehne G. Source: Clinical Pharmacology and Therapeutics. 2002 September; 72(3): 333-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235455

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Pharmacologic treatment of anal fissure with botoxin, diltiazem, or bethanechol. Author(s): Phillips R. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2002 May-June; 6(3): 281-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022973

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pH-dependent block of the L-type Ca2+ channel current by diltiazem in human mesenteric arterial myocytes. Author(s): Smirnov SV, Aaronson PI. Source: European Journal of Pharmacology. 1998 October 30; 360(1): 81-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9845276

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PK/PD modelling of high-dose diltiazem--absorption-rate dependency of the hysteresis loop. Author(s): Luckow V, Della Paschoa O. Source: Int J Clin Pharmacol Ther. 1997 October; 35(10): 418-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9352390

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Possible role of diltiazem in a recalcitrant case of Darier's disease. Author(s): Lorentzen H, Svejgaard E. Source: Acta Dermato-Venereologica. 2001 October-November; 81(5): 379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11800156

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Potentially fatal interaction between diltiazem and statins. Author(s): Gladding P, Pilmore H, Edwards C. Source: Annals of Internal Medicine. 2004 April 20; 140(8): W31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096363

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Potentiation of the antiproliferative activity of MKT-077 by loperamide, diltiazem and tamoxifen. Author(s): Abdul M, Hoosein N. Source: Oncol Rep. 2003 November-December; 10(6): 2023-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534737

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Prehospital use of intravenous diltiazem (cardizem Lyo-Ject) in the treatment of rapid atrial fibrillation. Author(s): Abarbanell NR, Marcotte MA. Source: The American Journal of Emergency Medicine. 1997 October; 15(6): 618-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9337374

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Probable diltiazem-induced acute interstitial nephritis. Author(s): Abadin JA, Duran JA, Perez de Leon JA. Source: The Annals of Pharmacotherapy. 1998 June; 32(6): 656-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9640485

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Progress report on the Nordic diltiazem study (NORDIL): an outcome study in hypertensive patients. Author(s): Hedner T. Source: Blood Pressure. 1999; 8(5-6): 296-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10803490

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Prolongation of the QT interval related to cisapride-diltiazem interaction. Author(s): Thomas AR, Chan LN, Bauman JL, Olopade CO. Source: Pharmacotherapy. 1998 March-April; 18(2): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9545159

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Quantitation of diltiazem in human cardiac tissue using high-performance liquid chromatography. Author(s): Laer S, Scholz H, Uebeler P, Neumann J, Zimmermann N. Source: Journal of Chromatographic Science. 1997 March; 35(3): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9062986

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Quantitation of diltiazem in human plasma by HPLC using an end-capped reversedphase column. Author(s): Jensen BH, Larsen C. Source: Acta Pharm Nord. 1991; 3(3): 179-80. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1793512

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Randomised trial of effects of calcium antagonists compared with diuretics and betablockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Author(s): Hansson L, Hedner T, Lund-Johansen P, Kjeldsen SE, Lindholm LH, Syvertsen JO, Lanke J, de Faire U, Dahlof B, Karlberg BE. Source: Lancet. 2000 July 29; 356(9227): 359-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10972367

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Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure (Br J Surg 2002; 89: 413-17). Author(s): Balaji NS, Ahmad M. Source: The British Journal of Surgery. 2002 October; 89(10): 1325. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12296913

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Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure (Br J Surg 2002; 89: 413-17). Author(s): Briel JW, Zimmerman DD, Schouten WR. Source: The British Journal of Surgery. 2002 September; 89(9): 1193; Author Reply 11934. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190689

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Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure (Br J Surg 2002; 89: 413-17). Author(s): Acheson AG, Griffin N, Scholefield JH. Source: The British Journal of Surgery. 2002 September; 89(9): 1193; Author Reply 11934. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190688

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Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure. Author(s): Kocher HM, Steward M, Leather AJ, Cullen PT. Source: The British Journal of Surgery. 2002 April; 89(4): 413-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952579

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Rapid reversal of life-threatening diltiazem-induced tetany with calcium chloride. Author(s): Vinson DR, Burke TF, Sung HM. Source: Annals of Emergency Medicine. 1999 November; 34(5): 676-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10533019

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Regression of calcinosis associated with adult dermatomyositis following diltiazem therapy. Author(s): Vinen CS, Patel S, Bruckner FE. Source: Rheumatology (Oxford, England). 2000 March; 39(3): 333-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10788545

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Regression of calcinosis during diltiazem treatment in juvenile dermatomyositis. Author(s): Oliveri MB, Palermo R, Mautalen C, Hubscher O. Source: The Journal of Rheumatology. 1996 December; 23(12): 2152-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8970055

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Relative bioavailability of Cardizem CD and Tiazac controlled-release diltiazem dosage forms after single and multiple dosing in healthy volunteers. Author(s): Dimmitt DC, Bhargava VO, Arumugham T, Eller M, Weir SJ. Source: American Journal of Therapeutics. 1998 May; 5(3): 173-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099056

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Reliability and efficacy of metoprolol and diltiazem in patients having mild to moderate mitral stenosis with sinus rhythm. Author(s): Alan S, Ulgen MS, Ozdemir K, Keles T, Toprak N. Source: Angiology. 2002 September-October; 53(5): 575-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12365866

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Rhabdomyolysis associated with concurrent use of simvastatin and diltiazem. Author(s): Peces R, Pobes A. Source: Nephron. 2001 September; 89(1): 117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11528245

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Rhabdomyolysis with concurrent atorvastatin and diltiazem. Author(s): Lewin JJ 3rd, Nappi JM, Taylor MH. Source: The Annals of Pharmacotherapy. 2002 October; 36(10): 1546-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243603

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Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. Author(s): Sutton D, Butler AM, Nadin L, Murray M. Source: The Journal of Pharmacology and Experimental Therapeutics. 1997 July; 282(1): 294-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9223567

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Role of diltiazem in pregnant women with chronic renal disease. Author(s): Khandelwal M, Kumanova M, Gaughan JP, Reece EA. Source: J Matern Fetal Neonatal Med. 2002 December;12(6):408-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12683652

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Severe atenolol and diltiazem overdose. Author(s): Snook CP, Sigvaldason K, Kristinsson J. Source: Journal of Toxicology. Clinical Toxicology. 2000; 38(6): 661-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185975

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Silent ischemic interval on exercise test is a predictor of response to drug therapy: a randomized crossover trial of metoprolol versus diltiazem in stable angina. Author(s): Dwivedi SK, Saran RK, Mittal S, Gupta R, Narain VS, Puri VK. Source: Clin Cardiol. 2001 January; 24(1): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195606

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Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis. Author(s): Kanathur N, Mathai MG, Byrd RP Jr, Fields CL, Roy TM. Source: Tenn Med. 2001 September; 94(9): 339-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11550401

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Study of processing parameters influencing the properties of diltiazem hydrochloride microspheres. Author(s): Bhalerao SS, Lalla JK, Rane MS. Source: Journal of Microencapsulation. 2001 May-June; 18(3): 299-307. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11308221

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Successful combined therapy of nifedipine and diltiazem for severe hypertension in a maintenance hemodialysis patient. Author(s): Ikeda Y, Sakemi T, Yamada M, Matsumoto J, Yamaguchi K. Source: Clinical Nephrology. 1999 February; 51(2): 127-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10069650

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Successful use of iv diltiazem to control perioperative refractory complex atrial tachyarrhythmias in a patient with pneumoconiosis. Author(s): Tsou CH, Chiang CE, Liou JT, Hsin ST, Luk HN. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 January; 50(1): 36-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12514148

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Sustained-release diltiazem overdose. Author(s): Morimoto S, Sasaki S, Kiyama M, Hatta T, Moriguchi J, Miki S, Kawa T, Nakamura K, Itoh H, Nakata T, Takeda K, Nakagawa M. Source: Journal of Human Hypertension. 1999 September; 13(9): 643-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10482975

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Sustained-release diltiazem reduces myocardial ischemic episodes in end-stage renal disease: a double-blind, randomized, crossover, placebo-controlled trial. Author(s): Cice G, Di Benedetto A, D'Andrea A, D'Isa S, Ferrara L, Russo PE, Iacono A, Calabro R. Source: Journal of the American Society of Nephrology : Jasn. 2003 April; 14(4): 1006-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660335

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Switching from drip to oral diltiazem therapy. Author(s): Sorrentino MJ. Source: Postgraduate Medicine. 1998 October; 104(4): 37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9793553

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The effect of diltiazem, a calcium channel blocker, in asthmatic patients. Author(s): Quintieri F, D'Ambrosio A, Bachetoni A. Source: British Journal of Clinical Pharmacology. 2002 December; 54(6): 679-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492620

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The effect of ketoconazole and diltiazem on oestrogen metabolism in postmenopausal women after single dose oestradiol treatment. Author(s): Annas A, Carlstrom K, Alvan G, AL-Shurbaji A. Source: British Journal of Clinical Pharmacology. 2003 September; 56(3): 334-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919184

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The effects of diltiazem on hemodynamics and seizure duration during electroconvulsive therapy. Author(s): Wajima Z, Yoshikawa T, Ogura A, Imanaga K, Shiga T, Inoue T, Ogawa R. Source: Anesthesia and Analgesia. 2001 May; 92(5): 1327-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323371

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The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. Author(s): Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG. Source: The Journal of Clinical Investigation. 2002 April; 109(8): 1013-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956238

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The use of diltiazem for treating rapid atrial fibrillation in the out-of-hospital setting. Author(s): Wang HE, O'connor RE, Megargel RE, Schnyder ME, Morrison DM, Barnes TA, Fitzkee A. Source: Annals of Emergency Medicine. 2001 January; 37(1): 38-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145769

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Topical diltiazem and bethanechol decrease anal sphincter pressure and heal anal fissures without side effects. Author(s): Carapeti EA, Kamm MA, Phillips RK. Source: Diseases of the Colon and Rectum. 2000 October; 43(10): 1359-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11052511

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Topical diltiazem ointment in the treatment of chronic anal fissure. Author(s): Knight JS, Birks M, Farouk R. Source: The British Journal of Surgery. 2001 April; 88(4): 553-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298624

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Treatment of stable angina with low dose diltiazem in combination with the metabolic agent trimetazidine. Author(s): Manchanda SC. Source: International Journal of Cardiology. 2003 March; 88(1): 83-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12659989

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Treatment with taurine, diltiazem, and vitamin E retards the progressive visual field reduction in retinitis pigmentosa: a 3-year follow-up study. Author(s): Pasantes-Morales H, Quiroz H, Quesada O. Source: Metabolic Brain Disease. 2002 September; 17(3): 183-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12322788

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Unilateral gynecomastia induced by treatment with diltiazem. Author(s): Otto C, Richter WO. Source: Archives of Internal Medicine. 1994 February 14; 154(3): 351. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8297206

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Unusual electrocardiographic changes with propranolol and diltiazem overdosage: a case report. Author(s): Satar S, Acikalin A, Akpinar O. Source: American Journal of Therapeutics. 2003 July-August; 10(4): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845395

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Use of diltiazem in sport. Author(s): Richards HU, Grocutt M, McCabe M. Source: Bmj (Clinical Research Ed.). 1993 October 9; 307(6909): 940. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8241880

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Use of glucagon for acute intravenous diltiazem toxicity. Author(s): Mahr NC, Valdes A, Lamas G. Source: The American Journal of Cardiology. 1997 June 1; 79(11): 1570-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9185662

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Use of intravenous diltiazem in patients with acute coronary artery disease. Author(s): Jaffe AS. Source: The American Journal of Cardiology. 1992 March 6; 69(7): 25B-29B. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1543138

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Use of parent drug and metabolite data in bioavailability assessment of a novel diltiazem HCl once-daily product. Author(s): Eradiri O, Midha KK. Source: Pharmaceutical Research. 1995 December; 12(12): 2071-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786992

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Usefulness of diltiazem in reducing the incidence of acute tubular necrosis in EuroCollins-preserved cadaveric renal grafts. Author(s): Puig JM, Lloveras J, Oliveras A, Costa A, Aubia J, Masramon J. Source: Transplantation Proceedings. 1991 October; 23(5): 2368-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1926388

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Usefulness of diltiazem in the acute management of supraventricular tachyarrhythmias in the elderly. Author(s): Millaire A, Leroy O, de Groote P, Santre C, Ducloux G. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1996 March; 10(1): 11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8723165

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Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris. Author(s): Brouwer J, Viersma JW, van Veldhuisen DJ, Man in 't Veld AJ, Sijbring P, Haaksma J, Dijk WA, Lie KI. Source: The American Journal of Cardiology. 1995 October 15; 76(11): 759-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7572650

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Usefulness of sustained-release diltiazem for stable angina pectoris. Author(s): Klinke WP, Juneau M, Grace M, Kostuk WJ, Pflugfelder P, Maranda CR, Warnica W, Chin C, Annable L, Dempsey EE, et al. Source: The American Journal of Cardiology. 1989 December 1; 64(19): 1249-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2511743

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Variability in plasma lipoprotein profiles when comparing diltiazem and propranolol. Author(s): Labreche DG, Kondos GT, Bartels DW, Bauman JL. Source: The Annals of Pharmacotherapy. 1993 September; 27(9): 1048-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8219435

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Vasculitic leg ulcers associated with diltiazem. Author(s): Carmichael AJ, Paul CJ. Source: Bmj (Clinical Research Ed.). 1988 August 20-27; 297(6647): 562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3139213

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Vasculopathy in cyclosporine-treated renal allografts: possible protection by diltiazem. Author(s): Choy BY, Walker RG, Becker GJ. Source: Clinical Transplantation. 1994 June; 8(3 Pt 1): 271-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8061366

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Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring. Author(s): Kubota K, Pearce GL, Inman WH. Source: European Journal of Clinical Pharmacology. 1995; 48(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7621840

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Ventricular rate control and exercise performance in chronic atrial fibrillation: effects of diltiazem and verapamil. Author(s): Lundstrom T, Ryden L. Source: Journal of the American College of Cardiology. 1990 July; 16(1): 86-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2358610

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Verapamil or diltiazem for acute rate control. Author(s): Ben Zemenick R. Source: Annals of Emergency Medicine. 1997 September; 30(3): 354-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9287904

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Verapamil or diltiazem for acute rate control: which is best. Author(s): Ben Zemenick R. Source: The American Journal of Cardiology. 1995 September 15; 76(8): 638-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7677100

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Verapamil, diltiazem and nifedipine interactions with calmodulin stimulated (Ca2+ + Mg2+)-ATPase. Author(s): Kim HC, Raess BU. Source: Biochemical Pharmacology. 1988 March 1; 37(5): 917-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2964236

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Visual compatibility of diltiazem injection with various diluents and medications during simulated Y-site injection. Author(s): Gayed AA, Keshary PR, Hinkle RL. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1995 March 1; 52(5): 516-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7606558

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Visual compatibility of diltiazem with commonly used injectable drugs during simulated Y-site administration. Author(s): Zanetti LA. Source: Am J Hosp Pharm. 1992 August; 49(8): 1911. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1442831

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Widespread cutaneous vasculitis associated with diltiazem. Author(s): Sheehan-Dare RA, Goodfield MJ. Source: Postgraduate Medical Journal. 1988 June; 64(752): 467-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3211830

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

Finding Nutrition Studies on Diltiazem 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 “diltiazem” (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 “diltiazem” (or a synonym): •

Absorption of diltiazem in beagle dog from pulsatile release tablet. Author(s): Pharmaceutics Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan. Source: Ishino, R Yoshino, H Hirakawa, Y Noda, K Chem-Pharm-Bull-(Tokyo). 1992 November; 40(11): 3094-6 0009-2363

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Cardiovascular and pharmacokinetic interactions between nicorandil and adjunctive propranolol, atenolol or diltiazem in conscious dogs. Author(s): Pharmacology Department, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan, USA. [email protected] Source: Humphrey, S J Methods-Find-Exp-Clin-Pharmacol. 1998 November; 20(9): 77991 0379-0355

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Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium. Author(s): Discipline of Clinical Pharmacology, University of Newcastle and Department of Clinical Toxicology and Pharmacology, Newcastle Mater Misericordiae Hospital, Waratah, NSW, Australia. [email protected] Source: Isbister, G K Emerg-Med-J. 2002 July; 19(4): 355-7 1472-0205

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Duration of protection of calcium channel blockers against exercise-induced bronchospasm: comparison of oral diltiazem and inhaled gallopamil. Author(s): Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville 32610. Source: Massey, K L Harman, E Hendeles, L Eur-J-Clin-Pharmacol. 1988; 34(6): 555-9 0031-6970

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Effect of diltiazem and a prostaglandin derivative (PGBx) on platelet function during long-term storage. Author(s): Division of Blood Research, Letterman Army Institute of Research, San Francisco, California. Source: Smith, D J Odom, D G Cheney, B A Transfusion. 1989 February; 29(2): 153-8 0041-1132

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Nifedipine, verapamil and diltiazem block shock-wave-induced rises in cytosolic calcium in MDCK cells. Author(s): Department of Medical Education and Research, Veterans General HospitalKaohsiung, Taiwan. [email protected] Source: January, C R Chen, W C Wu, S N Tseng, C J Chin-J-Physiol. 1998 December 31; 41(4): 181-8 0304-4920

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Preliminary investigations in matrix-based tablet formulations of diltiazem hydrochloride containing succinic acid-treated methylcellulose. Author(s): Department of Pharmaceutical Technology, L. M. College of Pharmacy, Navarangpura, Ahmedabad, India. Source: Gohel, M C Patel, M M Chhabaria, M T Buaria, C P Pharm-Dev-Technol. 1998 November; 3(4): 453-9 1083-7450

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Serial changes of soluble endothelin-1 levels during myocardial ischaemiareperfusion. Effects of magnesium, diltiazem and a novel MAC-1 inhibitor. Author(s): Sinai Hospital, Baltimore, MD, USA. Source: Serebruany, V L Schlossberg, M L Edenbaum, L R Herzog, W R Gurbel, P A Pharmacol-Res. 1998 September; 38(3): 165-72 1043-6618

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Simvastatin and atorvastatin enhance hypotensive effect of diltiazem in rats. Author(s): Department of Pharmacology, Hokkaido College of Pharmacy, 7-1 Katsuraoka, Otaru 047-0264, Japan. Source: Marumo, H Satoh, K Yamamoto, A Kaneta, S Ichihara, K Yakugaku-Zasshi. 2001 October; 121(10): 761-4 0031-6903

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Studies in release behavior of diltiazem HCl from matrix tablets containing (hydroxypropyl)methyl cellulose and xanthan gum. Author(s): Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Navrangpura, India. Source: Gohel, M C Amin, A F Patel, K V Panchal, M K Boll-Chim-Farm. 2002 JanFebruary; 141(1): 21-8 0006-6648

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The effect of the specific PAF antagonist BN 52021 and the calcium blocker diltiazem on PAF induced arrhythmogenicity. Author(s): Dept. of Pharmacology, Martin Luther University, Halle, GDR. Source: Riedel, A Braquet, P Mest, H J Pharmacol-Res-Commun. 1987 October; 19(10): 703-12 0031-6989

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

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

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

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

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

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

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

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

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Minerals Calcium-Channel Blockers Source: Healthnotes, Inc.; www.healthnotes.com

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

A trifunctional catalyst for one-pot synthesis of chiral diols via Heck coupling-Noxidation-asymmetric dihydroxylation: application for the synthesis of diltiazem and taxol side chain. Author(s): Choudary BM, Chowdari NS, Madhi S, Kantam ML. Source: The Journal of Organic Chemistry. 2003 March 7; 68(5): 1736-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12608786

•

Antagonistic effects of epinephrine, glucagon and methylatropine but not calcium chloride against atrio-ventricular conduction disturbances produced by high doses of diltiazem, in conscious dogs. Author(s): Sabatier J, Pouyet T, Shelvey G, Cavero I. Source: Fundamental & Clinical Pharmacology. 1991; 5(2): 93-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2071087

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•

Applications of Lewis acids for the efficient syntheses of diltiazem, cephems, and taxoids. Author(s): Hashiyama T. Source: Medicinal Research Reviews. 2000 November; 20(6): 485-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11058893

•

Bis(benzylisoquinoline) analogs of tetrandrine block L-type calcium channels: evidence for interaction at the diltiazem-binding site. Author(s): Felix JP, King VF, Shevell JL, Garcia ML, Kaczorowski GJ, Bick IR, Slaughter RS. Source: Biochemistry. 1992 December 1; 31(47): 11793-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1332772

•

Blocking effect of diltiazem on thiopentone-induced vasoconstriction in isolated canine internal carotid arteries. Author(s): Tsuji T, Chiba S. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 1985 September; 5(3): 44650. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4030922

•

Comparison of blood pressure response to heat stress in sauna in young hypertensive patients treated with atenolol and diltiazem. Author(s): Luurila OJ, Kohvakka A, Sundberg S. Source: The American Journal of Cardiology. 1989 July 1; 64(1): 97-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2741821

•

Comparison of combination nifedipine-propranolol and diltiazem-propranolol with high dose diltiazem monotherapy for stable angina pectoris. Author(s): Morse JR. Source: The American Journal of Cardiology. 1988 November 15; 62(16): 1028-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3055924

•

Coronary vascular hemodynamic and permeability changes during reperfusion after no-flow ischemia in isolated, diltiazem-treated rabbit hearts. Author(s): Tilton RG, Williamson EK, Cole PA, Larson KB, Kilo C, Williamson JR. Source: Journal of Cardiovascular Pharmacology. 1985 May-June; 7(3): 424-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2410670

•

Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium. Author(s): Isbister GK.

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Source: Emergency Medicine Journal : Emj. 2002 July; 19(4): 355-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101159 •

Development of modified release diltiazem HCl tablets using composite index to identify optimal formulation. Author(s): Gohel MC, Patel MM, Amin AF. Source: Drug Development and Industrial Pharmacy. 2003 May; 29(5): 565-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12779286

•

Different effect of diltiazem and nifedipine on some central actions of ethanol in the rat. Author(s): Pucilowski O, Krzascik P, Trzaskowska E, Kostowski W. Source: Alcohol (Fayetteville, N.Y.). 1989 March-April; 6(2): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2713089

•

Diltiazem stimulates parathyroid hormone secretion in vivo whereas felodipine does not. Author(s): Villiger L, Casez JP, Takkinen R, Jaeger P. Source: The Journal of Clinical Endocrinology and Metabolism. 1993 April; 76(4): 890-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8473401

•

Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting. Author(s): Ahonen J, Olkkola KT, Salmenpera M, Hynynen M, Neuvonen PJ. Source: Anesthesiology. 1996 December; 85(6): 1246-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8968170

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Effects of diltiazem on bioenergetics, K+ gradients, and free cytosolic Ca2+ levels in rat brain synaptosomes submitted to energy metabolism inhibition and depolarization. Author(s): Dagani F, Feletti F, Canevari L. Source: Journal of Neurochemistry. 1989 November; 53(5): 1379-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2795006

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Effects of extracellular ionized calcium, diltiazem and cAMP on motility of human spermatozoa. Author(s): Aaberg RA, Sauer MV, Sikka S, Rajfer J. Source: The Journal of Urology. 1989 May; 141(5): 1221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2540352

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Effects of omega-conotoxin GVIA and diltiazem on double peaked vasoconstrictor responses to periarterial electric nerve stimulation in isolated canine splenic artery. Author(s): Yang XP, Chiba S.

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Source: British Journal of Pharmacology. 2000 January; 129(1): 47-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10694201 •

High-affinity binding of [3H]DTZ323 to the diltiazem-binding site of L-type Ca2+ channels. Author(s): Hagiwara M, Adachi-Akahane S, Nagao T. Source: European Journal of Pharmacology. 2003 April 11; 466(1-2): 63-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679142

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High-dose diltiazem prevents migration and proliferation of vascular smooth muscle cells in various in-vitro models of human coronary restenosis. Author(s): Voisard R, Koschnick S, Baur R, Vogel U, Mattfeldt T, Hemmer W, Hannekum A, Hoher M, Hombach V. Source: Coronary Artery Disease. 1997 March-April; 8(3-4): 189-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9237030

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Influence of Mg++ on the effect of diltiazem to increase dihydropyridine binding to receptors on Ca++-channels in chick cardiac and skeletal muscle membranes. Author(s): Maan AC, Ptasienski J, Hosey MM. Source: The Journal of Pharmacology and Experimental Therapeutics. 1986 December; 239(3): 768-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2432217

•

Long-term study of high-dose diltiazem in chronic stable exertional angina. Author(s): Hossack KF, Kannagi T, Day B, Bruce RA. Source: American Heart Journal. 1984 June; 107(6): 1215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6720548

•

Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of succinic acid-treated ispaghula husk. Author(s): Gohel MC, Amin AF, Chhabaria MT, Panchal MK, Lalwani AN. Source: Pharmaceutical Development and Technology. 2000; 5(3): 375-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10934737

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Pharmacokinetics of a novel diltiazem HCl extended-release tablet formulation for evening administration. Author(s): Sista S, Lai JC, Eradiri O, Albert KS. Source: Journal of Clinical Pharmacology. 2003 October; 43(10): 1149-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517197

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Potentially serious drug interactions secondary to high-dose diltiazem used in the treatment of pulmonary hypertension. Author(s): Clarke WR, Horn JR, Kawabori I, Gurtel S.

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Source: Pharmacotherapy. 1993 July-August; 13(4): 402-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8361869 •

Potentiation of harringtonine cytotoxicity by calcium antagonist diltiazem and biscoclaurine alkaloid cepharanthine in adriamycin-resistant P388 murine leukemia and K562 human leukemia cells. Author(s): Yamamoto S, Hui PZ, Fukuda Y, Tatsumi K, Mino M. Source: Biochem Int. 1989 June; 18(6): 1077-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2751676

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Promotion of calcification by imidazole and its suppression by diltiazem in the growth cartilage of rats with HEBP induced rickets. Author(s): Eguchi M, Kawamura H, Wada F, Shimauchi T, Shiota E, Shibata K, Sugioka Y. Source: International Orthopaedics. 1989; 13(3): 217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2513279

•

Protective effect of diltiazem on ultrastructural alterations induced by coronary occlusion and reperfusion in dog hearts. Author(s): Sashida H, Abiko Y. Source: Journal of Molecular and Cellular Cardiology. 1986 April; 18(4): 401-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3712450

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Responses of isolated and perfused dog coronary arteries to acetylcholine, norepinephrine, KCl, and diltiazem before and after removal of the endothelial cells by saponin. Author(s): Nakane T, Itoh N, Chiba S. Source: Heart and Vessels. 1986; 2(4): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3571105

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Steady-state pharmacokinetics of high-dose diltiazem hydrochloride (Cardizem CD) administered once daily in healthy volunteers. Author(s): Robbins-Weilert DK, Giesing DH, Weir SJ. Source: American Journal of Therapeutics. 1999 July; 6(4): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11329099

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Studies on interactions between functional medicines. I. Effects of Ginkgo biloba leaf diltiazem in rats. Author(s): Ohnishi N, Kusuhara M, Yoshioka Koishi T, Nakagawa M, Hori S, Matsumoto Yokoyama T.

foods or dietary supplements and extract on the pharmacokinetics of M, Kuroda K, Soga A, Nishikawa F, T, Yamashita M, Ohta S, Takara K,

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Source: Biological & Pharmaceutical Bulletin. 2003 September; 26(9): 1315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951478 •

Temperature-specific effects of adjuvant diltiazem therapy on myocardial energetics following potassium cardioplegic arrest. Author(s): Krukenkamp IB, Silverman NA, Sorlie D, Pridjian A, Levitsky S. Source: The Annals of Thoracic Surgery. 1986 December; 42(6): 675-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3789858

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The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets. Author(s): Eguchi M, Shibata K, Wada F, Kawamura H, Shimauchi T, Shiota E, Sugioka Y. Source: Acta Endocrinol (Copenh). 1986 September; 113(1): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3094310

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The effects of verapamil and diltiazem pretreatment on potassium release in dogs after the administration of succinylcholine. Author(s): Howie MB, Kramer MG, McSweeney TD. Source: Anesthesia and Analgesia. 1998 September; 87(3): 691-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9728855

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The protective effects of high dose ascorbic acid and diltiazem on myocardial ischaemia-reperfusion injury. Author(s): Demirag K, Askar FZ, Uyar M, Cevik A, Ozmen D, Mutaf I, Bayindir O. Source: Middle East J Anesthesiol. 2001 February; 16(1): 67-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11281049

•

Treatment of children with refractory acute lymphocytic leukemia with vincristine and diltiazem. Author(s): Bessho F, Kinumaki H, Kobayashi M, Habu H, Nakamura K, Yokota S, Tsuruo T, Kobayashi N. Source: Medical and Pediatric Oncology. 1985; 13(4): 199-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3859743

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/

•

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

•

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

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

The following is a specific Web list relating to diltiazem; 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 Raynaud's Disease Source: Healthnotes, Inc.; www.healthnotes.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Coenzyme Q10 Alternative names: CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Coq10 Alternative names: Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone Source: Healthnotes, Inc.; www.healthnotes.com Diltiazem Source: Healthnotes, Inc.; www.healthnotes.com Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html

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Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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 DILTIAZEM 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 “diltiazem” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on diltiazem, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Diltiazem By performing a patent search focusing on diltiazem, 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 diltiazem: •

Chiral resolution of an intermediate in diltiazem synthesis using lipase PS immobilized with sucrose Inventor(s): Hytonen; Martti (Espoo, FI), Kairisalo; Pekka (Helsinki, FI), Kanerva; Liisa (Littoinen, FI), Sundholm; Oskari (Turku, FI) Assignee(s): Orion-yhtyma Oy Fermion (Espoo, FI) Patent Number: 5,514,589 Date filed: March 22, 1994 Abstract: An enzymatic method for the preparation of (2S,3S)-threo-alkyl-2-hydroxy-3(4-methoxyphenyl)-3-(2-X-phenylthio)propio nate, where X=NO.sub.2, NH.sub.2, NHCOCH.sub.3, NHCOCF.sub.3, NHCO.sub.2 CH.sub.3, NHCO.sub.2 C(CH.sub.3).sub.3 or NHCHO and R is an alkyl group, e.g., CH.sub.3, or CH.sub.2 CH.sub.3 in an essentially anhydrous organic solvent is described. In this method a lipase which stereospecifically acylates the (2R,3R)-enantiomer of the racemic mixture is used. After enzymatic reaction, the (2S,3S)-enantiomer and the acylated (2R,3R)compound are separated, e.g., by flash-chromatography or by fraction crystallization of the (2S,3S)-compound from the reaction mixture. Excerpt(s): The separation of (.+-.)-2-hydroxy-3-(4-methoxyphenyl)-3-(2aminophenylthio)propionic acid and propionates is described in the patent publications DE 3,337,176 and U.S. Pat. No. 4,908,469, and the separation of the corresponding enantiomers of (2-nitrophenylthio)propionic acid based on the formation of the diastereomeric salts with optically active aminoacids (L-lysine) or tartaric acid is described in the publication Chem. Pharm. Bull. 37 (1989) 3204-3208. So far the only biocatalytical method for the manufacture of (2S,3S)-threo-alkyl-2-hydroxy-3-(4methoxyphenyl)-3-(2-X-phenylthio)propio nates describes the hydrolysis of the racemic threo-methyl-2-acyloxy-3-(4-methoxyphenyl)-3-(2-nitrophenylthio)propionate 2a catalyzed by lipase Chem. Pharm. Bull 37 (1989) 2876-2878!. The enzymatic hydrolysis proceeds slowly because the compounds of types 1 and 2 are dissolved poorly in water. This is why the reactions have to be performed in an organic solvent, which is saturated with water. Additionally, the reaction is based on the kinetic control. Thus the yield of the optically active product remains low, if its highest possible optical purity is intended to be reached. The object of this invention is the resolution of the racemic threo-alkyl-2hydroxy-3-(4-methoxyphenyl)-3-(2-X-phenylthio)propionates 1 with a simple enzymatic method, which is based on a biocatalytic, practically almost enantiospecific acylation reaction of the secondary hydroxyl group in position 2 of compound 1 in anhydrous organic solvents. Different organic solvents can be used as solvent. Because the proteins as enzymes do not dissolve in organic solvents, it must specifically be taken care that the substrates and products dissolve in the chosen solvent. The advantage of the method described is the stability of the compound 1 with regard to the subsequent reactions. The yields of the reactions are good under the mild conditions. It also is advantageous that the described biocatalytic resolution is based on the selective reaction of the "wrong" enantiomer of the racemate with the achiral substrate and not on the formation of diastereomers. The chemical resolution similar to the formation of diastereomers requires the availability of an optically pure compound (L-lysine, for example), dismounting of the diastereomer and isolation of the liberated L-lysine, for example, and recycling of it from one resolution to another. In the reaction the unacylated (2S,3S)-

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enantiomer can be used for the manufacture of (2S,3S)-cis-diltiazem using the method described later. Web site: http://www.delphion.com/details?pn=US05514589__ •

Composition of angiotensin-II receptor antagonists and calcium channel blockers Inventor(s): Wong; Pancras C. B. (Wilmington, DE) Assignee(s): E. I. du Pont de Nemours and Company (Wilmington, DE) Patent Number: 5,492,904 Date filed: July 28, 1994 Abstract: Novel pharmaceutical compositions containing a combination of an angiotensin-II antagonist and a calcium channel blocker such as 2-butyl-4 chloro-1-[2-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-5-(hydroxymethyl) imidazole, and diltiazem and the use of such compositions in the treatment of hypertension and congestive heart failure. Excerpt(s): This invention relates to novel pharmaceutical compositions containing an angiotensin-II receptor antagonist from a selected class in combination with a calcium channel blocker from a selected class useful for the treatment of hypertension and for the treatment of congestive heart failure. The selected class of angiotensin-II receptor antagonists and the selected class of calcium channel blockers essential as component parts of the novel compositions of this invention are compounds already known in the art as antihypertensive agents. Angiotensin-II receptor antagonists useful in compositions of the invention are included in those compounds disclosed in published European Published application 0 324 377 the disclosure of which is incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05492904__

•

Controlled absorption diltiazem pharmaceutical formulation Inventor(s): Heinicke; Grant Wayne (Fairview Park, AU), Lepore; Angelo (Magill, AU), Morella; Angelo Mario (Campbelltown, AU) Assignee(s): FH Faulding & Co. Limited (Parkside, AU) Patent Number: 5,834,024 Date filed: March 10, 1997 Abstract: A controlled absorption diltiazem pellet formulation for oral administration comprises a core having diltiazem or a pharmaceutically acceptable salt thereof as the active ingredient. The core is surrounded by a coating which has only a single layer which is comprised of a relatively major proportion of talc and relatively minor proportion of sodium lauryl sulfate admixed with a minor proportion of a pharmaceutically acceptable film-forming, first polymer permeable to water and diltiazem, and a major proportion of a pharmaceutically acceptable film-forming, second polymer that is less permeable to water and diltiazem than the first polymer. The core and the coating layer both exclude organic acids. The composition of the coating layer as well as the proportion of core to coating layer are effective to permit release of the diltiazem allowing controlled absorption following oral administration.

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By combining short lag and long lag pellets into a single formulation, the release of diltiazem is controlled over a twenty four hour period. Excerpt(s): The present invention relates to controlled absorption pharmaceutical formulations and, in particular, to controlled absorption forms of diltiazem for once a day oral administration. Diltiazem, which is cis-(+)-3-(acetyloxy)-5-›2(dimethylamino)ethyl!-2,3-dihydro- 2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one, referred to herein as "diltiazem", is a benzothiazine derivative possessing calcium antagonist activity. Diltiazem blocks the influx of calcium ions in smooth and cardiac muscle and thus exerts potent cardiovascular effects. Diltiazem has been shown to be useful in alleviating symptoms of chronic heart disease, particularly angina pectoris and myocardial ischemia and hypertension, while displaying a low incidence of side effects. Diltiazem is available as diltiazem hydrochloride in tablet form in strengths of 30, 60, 90 and 120 mg. and in capsule form in strengths of 60, 90, 120, 180, 240 and 300 mg. Diltiazem is also available in injectable form with a strength of 5 mg./ml. Diltiazem therapy typically starts with 30 mg. administered 4 times daily. The dosage is gradually increased to 180 to 360 mg./day, given in divided doses three or four times daily, at oneto two- day intervals until an optimum response is obtained. Diltiazem is extensively metabolized by the liver. According to professional use information issued by Marion Merrell Dow Inc., diltiazem in CARDIZEM.RTM. brand tablets is absorbed to about 80% and is subject to an extensive first-pass effect, giving an absolute bioavailability, compared to intravenous administration, of about 40%. Single oral doses of 30 to 120 mg. of CARDIZEM.RTM. diltiazem tablets result in peak plasma levels two to three hours after administration. Detectable plasma levels occur within 30 to 60 minutes after administration indicating that CARDIZEM.RTM. diltiazem tablets are readily absorbed. The plasma elimination half-life following single or multiple administration is approximately 3.5 hours. Therapeutic blood levels of CARDIZEM.RTM. diltiazem tablets appear to be in the range of 50 to 200 ng./ml. Web site: http://www.delphion.com/details?pn=US05834024__ •

Controlled absorption diltiazen formulation for once-daily administration Inventor(s): Geoghegan; Edward J. (Athlone, IE), Mulligan; Seamus (Gainesville, GA), Panoz; Donald E. (Tuckerstown, BM) Assignee(s): Elan Corporation PLC (Athlone, IE) Patent Number: 5,616,345 Date filed: November 4, 1994 Abstract: A diltiazem pellet formulation for oral administration comprises a core of diltiazem or a pharmaceutically acceptable salt thereof in association with an organic acid, and a multi-layer membrane surrounding the core and containing a major proportion of a pharmaceutically acceptable film-forming, water insoluble synthetic polymer and a minor proportion of a pharmaceutically acceptable film-forming, water soluble synthetic polymer. The number of layers in the membrane and the ratio of the water soluble to water insoluble polymer being effective to permit release of the diltiazem from the pellet at a rate allowing controlled absorption thereof over a twenty four hour period following oral administration. Excerpt(s): This invention relates to a controlled absorption pharmaceutical formulation and, in particular, to a controlled absorption form of diltiazem for oral administration. Diltiazem-cis-(+)-3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4 -

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methoxyphenyl)-1,5-benzothiazepin-4(5H)-one, is a benzothiazine derivative possessing calcium antagonist activity. Diltiazem blocks the influx of calcium ions in smooth and cardiac muscle and thus exerts potent cardio-vascular effects. Diltiazem has been shown to be useful in alleviating symptoms of chronic heart disease, particularly angina pectoris and myocardial ischemia and hypertension, while displaying a low incidence of side effects. Diltiazem is conventionally administered in tablet form (30 mg or 60 mg) as diltiazem hydrochloride sold under the Trade Mark Cardizem (Marion Laboratories Inc.). Diltiazem in tablet form (30 mg) is also sold under the Trade Mark Herbesser (Tanabe Seiyaku). Diltiazem is also sold in capsule form. Conventional diltiazem therapy starts with 30 mg administered 4 times daily. The dosage is gradually increased to 240 mg, given in divided doses three or four times daily, at one-to two-day intervals until an optimum response is obtained. Diltiazem is extensively metabolized by the liver and excreted by the kidneys and in bile. According to professional use information issued by Marion Laboratories Inc., Cardizem is absorbed from the known tablet formulation to about 80% and is subject to an extensive first-pass effect, giving an absolute bioavailability, compared to intravenous administration, of about 40%. Single oral doses of 30 to 120 mg of Cardizem result in peak plasma levels 2-3 hours after administration. Detectable plasma levels occur within 30-60 minutes after administration indicating that Cardizem is readily absorbed. Web site: http://www.delphion.com/details?pn=US05616345__ •

Controlled drug delivery system for diltiazem Inventor(s): Nagaprasad; Vishnubhotla (Warangal, IN), Sen; Himadri (Gurgaon, IN) Assignee(s): Ranbaxy Laboratories Limited (New Delhi, IN) Patent Number: 6,074,669 Date filed: December 4, 1997 Abstract: A pharmaceutical composition in the form of a tablet or a capsule for the controlled release of diltiazem, comprises about 30 to about 97% by weight of a hydrophilic polymer, about 0.5 to about 30% by weight of an enteric (pH-dependent) polymer, and about 2.5 to about 60% by weight of diltiazem or a pharmaceutically acceptable salt or ester thereof. The ratio of hydrophilic polymer to enteric polymer is in the range of about 1:1 to about 15:1. Such a pharmaceutical composition releases diltiazem at a rate that allows effective plasma levels of diltiazem to be maintained over a period of twenty-four hours after administration to human adult subjects. Excerpt(s): This invention relates to a pharmaceutical composition of a controlled release drug delivery system in the form of tablets or capsules comprising one or more of a hydrophilic polymer present in amounts greater than 30% (e.g., about 30 to 97%) by weight, an enteric polymer which is present in amounts from about 0.5 to 30% by weight, and diltiazem or a pharmaceutically acceptable salt or ester thereof in amounts from about 2.5 to 60% by weight, said % by weight being based on the total weight of the composition. The ratio of hydrophilic polymer to enteric polymer is in the range of about 1:1 to 15:1, such that diltiazem is released at a rate that allows effective plasma levels of diltiazem to be maintained over a period of twenty four-hours postadministration to human subjects. Diltiazem hydrochloride, a benzothiazepine derivative, is a calcium channel blocker used in the treatment of angina and hypertension. The solubility of diltiazem significantly decreases as the pH increases in the gastrointestinal tract. It is required, however, that a drug delivery system deliver the drug at a constant rate as it is transported from the region of low pH in the stomach to a

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region of higher pH in the intestine. Such controlled delivery results in a decrease in the frequency of drug administration thereby improving patient compliance. Furthermore, controlled drug delivery systems produce constant plasma levels of active ingredients as compared to fluctuations seen when multiple doses of a conventional formulation are prescribed. Thus, controlled drug delivery systems may decrease the severity and frequency of side effects. Several controlled drug delivery systems which are adapted for the delivery of the drug diltiazem and other drugs are known in the prior art. Web site: http://www.delphion.com/details?pn=US06074669__ •

Controlled release formulation of diltiazem hydrochloride Inventor(s): Sherman; Bernard C. (50 Old Colony Rd., North York, Ontario, CA) Assignee(s): none reported Patent Number: 5,578,321 Date filed: May 11, 1995 Abstract: A pharmaceutical tablet containing diltiazem hydrochloride suitable for once daily oral administration comprising by weight not less than 30 percent diltiazem hydrochloride and from 30 percent to 70 percent hydroxypropyl methylcellulose having a number average molecular weight of at least 50,000. A two piece hard gelatin capsule containing a plurality of such tablets. Excerpt(s): This invention relates to a controlled release pharmaceutical formulation of diltiazem hydrochloride suitable for once daily oral administration. Diltiazem is a benzothiazine derivative possessing calcium antagonist activity. Diltiazem blocks the influx of calcium ions in smooth and cardiac muscle and thus exerts potent cardiovascular effects. Diltiazem has been shown to be useful in alleviating symptoms of chronic heart disease, particularly angina pectoris and myocardial ischemia and hypertension, while displaying a low incidence of side effects. The first dosage forms of diltiazem sold in the United States were tablets containing 30 mg or 60 mg of diltiazem hydrochloride sold under this tradename Cardizem by Marion Laboratories Inc. Single oral doses of 30 mg to 120 mg of Cardizem tablets result in peak plasma level about 2 to 3 hours after ingestion, and the elimination half-life is about 3 to 5 hours. Because of the relatively rapid absorption of diltiazem from such tablets and rapid elimination, the usual dosage regimen for such tablets is for the daily dosage to be taken in divided doses, three or four times daily. The need for such frequent administration may reduce patient compliance and produce irregular blood levels. Thus adverse therapeutic effects can arise. It thus became apparent that it would be preferable to administer diltiazem hydrochloride in a dosage form that releases the diltiazem hydrochloride much more slowly than Cardizem tablets, so as to enable the frequency of ingestion by the patient to be reduced from three or four times daily to once daily. A dosage form of diltiazem hydrochloride that controls the rate of release to enable once daily administration is now sold in the United States under the trademark Cardizem CD, also by Marion Laboratories Inc. Cardizem CD is sold as capsules containing a multitude of pellets. The pellets are made using core seeds to which is applied a first coating containing the diltiazem hydrochloride. Over the first coating, further coatings of polymers are applied which serve to slow down and control the rate at which the diltiazem hydrochloride is released from the pellets in gastrointestinal fluids. The composition of the pellets contained in Cardizem CD capsules is described,in more detail in U.S. Pat. No. 4,894,240. While the formulation of Cardizem CD capsules successfully accomplishes

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gradual release to enable once daily administration, the procedures required to make and coat the pellets are time consuming and expensive. Web site: http://www.delphion.com/details?pn=US05578321__ •

Delayed, sustained-release diltiazem pharmaceutical preparation Inventor(s): Cobb, Jr.; Joseph E. (Columbus, OH), Eichel, deceased; Herman J. (late of Columbus, OH), Massmann; Brent D. (Ballwin, MO) Assignee(s): Kinaform Technology, Inc. (Dayton, OH) Patent Number: 5,529,790 Date filed: December 12, 1994 Abstract: A delayed, sustained-release pharmaceutical preparation is provided in which a water-soluble drug core is surrounded by a hydratable diffusion barrier which delays drug release for about 2-10 hours. The hydratable diffusion barrier comprises a filmforming polymer such as an acrylic resin, esterified acrylic resin, or ethyl cellulose or mixtures thereof and an additive which controls the rate of hydration and permeability of the hydratable diffusion barrier selected from the group consisting of lubricants, anionic surfactants, plasticizers, inert water-soluble materials, and mixtures thereof. In the preferred sustained-release pharmaceutical preparation, the film-forming polymer is combined with the additive and coated onto core drug granules to produce a diffusion barrier surrounding the core drug and form microparticles when the drug core is the preferred diltiazem hydrochloride, different coating thicknesses of the diffusion barrier are used to provide a long delay component and a short delay component. Excerpt(s): The present invention relates to delayed, sustained-release pharmaceutical preparations, and more particularly, to microparticles or tablets formed of a diltiazem core drug coated with a single, hydratable diffusion barrier which allows a prolonged delayed and sustained release drug delivery. As is well known, the maximum time of effectiveness in many pharmaceutical preparations, particularly those containing a drug such as aspirin, acetaminophen, indomethacin, propranolol hydrochloride, dextromethorphan, diltiazem etc. is only a few hours because of biological modification and/or elimination of the medication in the body. Consequently, repeated doses must be taken at frequent intervals to obtain long term therapeutic levels of drug. Furthermore, these drugs usually dissolve readily in the digestive juices and the total dosage is immediately fed into the blood stream. After high initial peak concentrations, the level of drug in the blood stream constantly decreases because of the biological elimination, so there is little or no therapeutic effect at the end of the period between doses. As a result, the therapeutic effect fluctuates between doses corresponding to the peaks and valleys in the level of drug in the blood. Many attempts have been made to develop timed-release pharmaceutical preparations which provide a more constant level of the drug in the blood over several hours. Web site: http://www.delphion.com/details?pn=US05529790__

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Diltiazem controlled release formulation Inventor(s): Chen; Chih-Ming (Cooper City, FL) Assignee(s): Andrx Pharmaceuticals Inc. (Ft. Lauderdale, FL) Patent Number: 5,567,441 Date filed: March 24, 1995 Abstract: A once-a-day controlled release diltiazem formulation is described which includes:(a) from 20 to 50% by weight of enteric polymeric membrane coated pellets comprising a polymer membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder; and a second layer which comprises a membrane comprising a pH dependent polymeric material; and(b) from 50% to 80% by weight of delayed pulse polymeric membrane coated pellets comprising a polymeric membrane coated core which comprises a biologically inert core which is coated with a first layer which consists essentially of diltiazem and a polymeric binder and a second layer which comprises a polymeric membrane which will substantially maintain its integrity in the varying pH conditions of the gastrointestinal tract but is permeable to diltiazem; and(c) a unit dose containment system. Excerpt(s): The present invention relates to controlled release unit dose formulations of diltiazem hydrochloride (diltiazem). Diltiazem is sold commercially in extended release pharmaceutical dosage forms in order to maintain a therapeutic serum level of diltiazem and to minimize the effects of missed doses of drugs caused by a lack of patient compliance. The minimum therapeutic plasma diltiazem concentrations are in the range of 50 to 200 ng/ml. In the prior art extended release formulations of diltiazem tablets have been marketed which provide 24 hour therapeutic blood levels of diltiazem with once a day administration of a single dosage unit. Cardizem.RTM. CD is described as a once-a-day extended release capsule containing diltiazem and fumaric acid. In the file history of U.S. Pat. No. 5,286,497, representations were made that the formulation disclosed in that patent is the formulation for Caridizem.RTM. CD. The formulation for Cardizem.RTM. CD is identified in the file history of U.S. Pat. No. 5,286,497 as having a "stair-step release profile" which has a rapid release bead and an extended release bead. The other commercially available diltiazem once-a-day formulation is sold under the Dilacor XR.RTM. trademark. This formulation is described as being based on the Geomatrix" controlled release system which is described in U.S. Pat. No. 4,839,177. Web site: http://www.delphion.com/details?pn=US05567441__

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Diltiazem formulation Inventor(s): Baltezor; Michael J. (Lees Summit, MO), Dimmitt; Dan C. (Belton, MO), Hendrickson; Dennis L. (Overland Park, KS), Skultety; Paul F. (Leawood, KS), Williams; Mark S. (Kansas City, MO) Assignee(s): Carderm Capital L.P. (CH) Patent Number: 5,439,689 Date filed: December 8, 1993 Abstract: The present invention is directed to a diltiazem formulation suitable for one a day administration. The formulation contains a blend of diltiazem beads having two differing dissolution profiles.

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Excerpt(s): The present invention is directed to diltiazem beads suitable for incorporation into a controlled release diltiazem formulation. Another aspect of this invention is directed to diltiazem formulations suitable for once a day administration. Diltiazem, (+) cis 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4methoxyphenyl)-1 ,5-benzothiazepin-4(5H)one, is a calcium antagonist that is marketed by Marion Merrell Dow under the tradename Cardizem.RTM. The compound can be utilized in the treatment of cardiovascular disorders such as angina, arrhythmias, and hypertension. Typical doses range from 120-360 mg/day. Cardizem.RTM. is currently commercially available in two dosage forms in the United States. One of the forms is a rapid release tablet which must be administered from 3-4 times daily. The other is a sustained release tablet which is suitable for bid dosage regimens. A formulation suitable for once a day (qd) administration is not currently commercially available in the United States. Numerous studies have shown that patient compliance increases substantially with medication regimens requiring only one dose per day. Thus it would be a valuable contribution to the art to develop a diltiazem formulation suitable for qd administration. The pharmacokinetics of a drug can have a considerable impact on whether a particular dosage form will produce satisfactory results after in-vivo administration. Orally administered drugs are absorbed and enter the capillaries and veins of the upper GI tract and are transported by the portal vein directly to the liver before entering the general circulation of the body. The entire absorbed dose of a drug is exposed to the liver during its first pass through the body. If a drug is Subject to a high hepatic clearance (ie. rapidly metabolized by the liver), then a substantial fraction of the absorbed dose is extracted from the blood and metabolized before it reaches the systemic circulation. This phenomenon is termed the first pass effect. The consequence of this phenomenon is a significant decrease in bioavailability. In some instances, the first pass effect is so large as to render oral administration of a drug ineffectual. Web site: http://www.delphion.com/details?pn=US05439689__ •

Enteric coated diltiazem once-a-day formulation Inventor(s): Chen; Chih-Ming (Davie, FL) Assignee(s): Andrx Pharmaceuticals, Inc. (Fort Lauderdale, FL) Patent Number: 5,830,503 Date filed: June 21, 1996 Abstract: A once-a-day diltiazem dosage form which comprises: (a) a core element which is a compressed tablet which contains a therapeutic dose of diltiazem and an amount of a solubility modulating substance that controls the release of said diltiazem in order to provide a therapeutic level over a period of about 24 hours; and (b) on the outer surface of the core element, a sufficient amount of an enteric coating that causes the diltiazem to release at a rate that permits the use of once-a-day dosing to maintain steady state therapeutic levels of diltiazem. Excerpt(s): The present invention relates to controlled release unit dose formulations of diltiazem hydrochloride (diltiazem). Diltiazem is sold commercially in extended release pharmaceutical dosage forms in order to maintain a therapeutic serum level of diltiazem and to minimize the effects of missed doses of drugs caused by a lack of patient compliance. The minimum therapeutic plasma diltiazem concentrations are in the range of 50 to 200 ng/ml. In the prior art extended release formulations of diltiazem tablets have been marketed which provide 24 hour therapeutic blood levels of diltiazem with once a day administration of a single dosage unit. These tablets are known as

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Dilacor XR.RTM. This product is described as a once-a-day capsule which contains multiple units of diltiazem hydrochloride. This product is also described in U.S. Pat. No. 4,839,177 which discloses that the tablet comprises a core of diltiazem hydrochloride and a swellable polymer and a support platform applied to the tablet. The support platform is described in the text of U.S. Pat. No. 4,839,177 as being "inert and insoluble in the medium into which the active substance is to be transferred". In U.S. Pat. No. 5,229,135, a once-a-day formulation is described that is based on a single pellet which is prepared with an active core which is coated with diltiazem and an inner and outer membrane. Web site: http://www.delphion.com/details?pn=US05830503__ •

Extended release form of diltiazem Inventor(s): Baudier; Philippe R. (Waterloo, BE), Deboeck; Arthur M. (Gurabo, PR) Assignee(s): Galephar P.R., Inc., Ltd. (Carolina, PR) Patent Number: 5,529,791 Date filed: September 23, 1994 Abstract: An extended-release galenical form of Diltiazem or a pharmaceutically acceptable salt thereof, which comprises beads containing said Diltiazem or a pharmaceutically acceptable salt thereof as an active ingredient and a wetting agent, said beads being coated with a microporous membrane comprising at least a watersoluble or water-dispersible polymer or copolymer and a pharmaceutically acceptable adjuvant. Excerpt(s): The present invention relates to an extended release form of Diltiazem, a process for the manufacture thereof and pharmaceutical compositions containing the same. Diltiazem hydrochloride is used in medicine principally for its calcium channel blocking properties, and, therefore, finds application in the treatment of angina pectoris and hypertension; either alone or in combination with other medications. Although the mechanism for calcium channel blocking is not completely understood, calcium ion entry is believed to be inhibited through select voltage, with the sensitive areas termed "slow channels", across cell membranes. By reducing intracellular calcium concentration in cardiac and vascular smooth muscle cells, coronary arteries, peripheral arteries and arterioles are dilated and heart rate may be reduced. Also, myocardial contractibility may be decreased and atrioventricular nodal conduction may be slowed. The activity of diltiazem in human is directly related to its blood or plasma concentration. Web site: http://www.delphion.com/details?pn=US05529791__

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Method for the manufacture of benzothiazepine Inventor(s): Andrew; Burchat (Guelph, CA), Murthy; Keshava (Brantford, CA), Weeratunga; Gamini (Brantford, CA) Assignee(s): ACIC (Canada) Inc. (Brantford, CA) Patent Number: 5,559,229 Date filed: June 1, 1995 Abstract: A process for the manufacture of Diltiazem or deacetyl-Diltiazem, which comprises the use of MIBK as solvent and NaOH as base.

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Excerpt(s): This invention relates to a novel process for the manufacture of Benzothiazepine derivatives and finds particular application in the manufacture of Diltiazem and intermediates readily converted to Diltiazem. Diltiazem is offered for sale as the hydrochloride salt thereof. In subsequent processes developed, the use of the lactam and dimethylaminoethyl chloride in an N-alkylation step has become the most popular and preferred route for the ultimate manufacture of Diltiazem. (In this process the produced intermediates are acylated to produce Diltiazem.) The N-alkylation step is carried out in the presence of a base and solvent. In some of the N-alkylation steps, the process is carried out in the presence of a phase transfer catalyst. Web site: http://www.delphion.com/details?pn=US05559229__ •

Method of treating hyperactive voiding with calcium channel blockers Inventor(s): Steers; William D. (Charlottesville, VA), Tuttle; Jeremy B. (Earlysville, VA) Assignee(s): UVA Patent Foundation (Charlottesville, VA) Patent Number: 5,698,549 Date filed: June 7, 1995 Abstract: The instant invention discloses a method of treating hyperactive voiding associated with excessive nerve growth factor production and nerve growth in patients by administering a Ca.sup.++ channel blocker. The Ca.sup.++ channel blockers verapamil and diltiazem can be administered systemically to treat hyperactive voiding, such as is associated with benign prostatic hyperplasia and interstitial cystitis. Excerpt(s): The invention relates to the use of Ca.sup.++ -channel blockers is disclosed to inhibit the production of NGF and nerve growth. Additionally, the isolation of markers in urine to indicate the presence of irritative and/or obstructive conditions in the bladder. Historically, there has been a progression from anatomical to functional studies for the diagnosis of upper and lower urinary tract obstruction. However, these studies fail to predict ultimate changes in bladder or kidney function. For example, with obstruction of the lower urinary tract, urodynamic studies often do not correlate with the severity of symptoms and fail to demonstrate capacity for return to normal function following relief of obstruction. Two major classes of voiding disorder in males and females are benign prostatic hyperplasia (BPH) and interstitial cystitis (IC). These cause, respectively, irritative/obstructive symptomology and idiopathic bladder and pelvic pain with voiding. An accumulating body of information links these conditions to changes in bladder innervation and that these may be orchestrated by neurotrophic factors. Web site: http://www.delphion.com/details?pn=US05698549__

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Pharmaceutical spheroid formulation Inventor(s): Buxton; Ian R. (Cambridge, GB), Critchley; Helen (Cambridge, GB), Leslie; Stewart T. (Cambridge, GB), Malkowska; Sandra T. A. (Cambridge, GB), Miller; Ronald B. (Basle, CH), Prater; Derek A. (Cambridge, GB) Assignee(s): Euro-Celtique, S.A. (LU) Patent Number: 5,601,845 Date filed: June 18, 1996

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Abstract: A controlled release composition including spheroid cores of diltiazem. or a pharmaceutically acceptable salt thereof and optionally a spheronizing agent, the cores being coated with a controlled release layer, and a method of manufacturing the same, is disclosed. The spheronizing agent when present is preferably microcrystalline cellulose. Ethylcellulose is a preferred release coating. The controlled release coating preferably contains a plasticizer, a surfactant and a tack-modifier. Excerpt(s): The present invention relates to a controlled release preparation and to a process for its preparation. In particular it relates to a controlled release preparation containing diltiazem. Diltiazem is a calcium antagonist which has been shown to be useful in treating chronic heart disease such as hypertension and angina. It is an object of the present invention to provide a controlled release diltiazem preparation suitable for once daily administration for the treatment of hypertension and angina. Web site: http://www.delphion.com/details?pn=US05601845__ •

Process for preparing a retard product containing diltiazem for a single daily administration Inventor(s): Barth; Dieter (Erbach, DE) Assignee(s): Farmarc Nederland B.V. (Amsterdam, NL) Patent Number: 5,622,716 Date filed: April 23, 1996 Abstract: This invention is directed towards pellets and a process for manufacturing pellets of diltiazem HCl having a dissolution kinetic independent from pH. Excerpt(s): Diltiazem, 3-(acetyloxy)-5-[2-(dimethylamino)-ethyl)-2, 3-dihydro-2- (4metoxyphenyl)-1,5-benzotiazepin-4 (5H)-one acetate, is efficacious in angina and hypertension. It is normally used as hydrochloride. Diltiazem HCl is a white crystalline powder, freely soluble in water. Because of its physico-chemical characteristics, diltiazem is a substance with a pH-dependent solubility. Web site: http://www.delphion.com/details?pn=US05622716__

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Process for preparing diltiazem Inventor(s): Hytonen; Martti (Espoo, FI) Assignee(s): Orion-Yhtyma Oy Fermion (Espoo, FI) Patent Number: 5,644,054 Date filed: February 14, 1996 Abstract: A process is provided for preparing cis-(+)-hydroxy-5-[2(dimethylamine)ethyl]-2,3-dihydro-2-(4-methoxyphenyl) -benzothiazepin-4(5H)-one that is a useful intermediate in the preparation of diltiazem. It has been found that the requisite N-alkylation reaction proceeds rapidly and with an excellent yield when the solvent is a mixture of toluene and N-methylpyrrolidin-2-one and the base is finelydivided sodium carbonate under anhydrous conditions. Such diltiazem commonly is used in the treatment of angina pectoris. Excerpt(s): Dimethyl sulfoxide, toluene, xylene, and dioxane are described as possible solvents in this N-alkylation reaction. The base used in the reaction described in U.S.

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Pat. No. 3,562,257 is metallic sodium, sodium amide or sodium hydride. According to the patent, in particular dimethyl sulfoxide together with sodium hydride is especially well suited for this reaction. In connection with this reaction there is an evident risk of explosion (Chem. Eng. News, 44 (15), 48 (1966)) and, furthermore, dimethyl sulfoxide is difficult to regenerate, since it dissolves completely in water and its boiling point is high. Patent EP 81234 describes an improved N-alkylation process, by which the disadvantages of the method according to the above-mentioned patent are avoided. In this process, compound (III) reacts with compound (IV), thereby forming compound (I). The reaction is carried out in the presence of potassium hydroxide in acetone or in the presence of potassium carbonate in a solvent which has been selected from among acetone, a lower alkyl acetate, a mixture of water and acetone, or a mixture of a lower alkyl acetate and water. However, when applied on an industrial scale, this process has severe disadvantages. In all of the processes described in the examples, the product is crystallized out, after a plurality of treatment steps, as its hydrochloride from ethanol in order that a sufficiently pure intermediate should be obtained. When acetone is used as the solvent, the after-treatment is complicated, since acetone is completely miscible with water and conventional removal of the salts cannot be carried out using water. The solvent must first be replaced with, for example, toluene, which is further, after the washing out of the salts, replaced with ethanol in order that the product could be crystallized and thereby freed of impurities. In all of the examples described in the patent, solvent is used in the alkylation reaction in an 8- to 10-fold amount in milliliters per one gram of the initial material to be alkylated. In the description section of the patent, the amount of solvent is limited to 5- to 15-fold in proportion to the initial material. On the basis of our laboratory experiments, those examples according to the patent in which the solvent is acetone or ethyl acetate and the base is potassium carbonate do not work repeatably. The reaction time in the examples of the patent varies from three hours in Example 2 to 30 hours in Example 7. If the time required by the reaction, the amount of solvent used in the reaction, and the cumbersome and complicated after-treatment are taken into consideration, these processes require a great deal of production capacity, working hours, and energy. Furthermore, ethylacetate hydrolyzes in alkaline conditions, and therefore its regeneration for reuse is problematic. In U.S. Pat. No. 3,562,257, the alkylation of intermediate (III) takes place by the use of a base form of compound (IV), as also in patent application EP 594101, in which the N-alkylation reaction is carried out in toluene with sodium carbonate serving as the base. Web site: http://www.delphion.com/details?pn=US05644054__ •

Process for preparing optically active glycidate esters Inventor(s): Brandt; Steven (Marlborough, MA), Dodds; David Richard (Millis, MA), Lopez; Jorge Luis (Framingham, MA), Zepp; Charles Melvyn (Berlin, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,521,445 Date filed: April 10, 1989 Abstract: This invention relates to a method for the production of (2R,3S)-3-(4methoxyphenyl)glycidic acids and esters thereof, which are synthetic intermediates for the production of the calcium antagonist diltiazem. The method involves the stereoselective enzymatic ester hydrolysis of racemic trans-3-(4-methoxyphenyl)glycidic acid ester to yield the resolved (2R,3S) compound as the ester. Membrane reactor

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methods and apparatus for the conduct of this enzymatic resolution process are also disclosed herein, as is the use of bisulfite anion in the aqueous reaction phase as a means of minimizing the inhibitory effect of an aldehyde reaction by-product on the reaction's progress. The benefits of selected solvent systems from which may be obtained highly resolved ester product are also disclosed. These enriched organic solutions may be used in subsequent transformations. Alternatively, optically pure product may be obtained directly therefrom. Excerpt(s): The esters of trans-3-(4-methoxyphenyl)glycidic acid have utility as precursors in the chemical synthesis of diltiazem. Moreover, these compounds present a very attractive point in the overall synthetic route to diltiazem at which to introduce the desired stereochemistry into the diltiazem precursors through resolution of the racemic glycidic esters and use of the correct, optically purified precursor ester. The present invention pertains to a novel enzymatic method for resolving a racemic mixture of esters of the (2R,3S)- and (2S,3R)-enantiomers of trans-3-(4-methoxyphenyl)glycidic acid. It also pertains to a process for diltiazem production incorporating this resolution step and to membrane reactor means for improving the efficiency of enzymatic resolution of this diltiazem intermediate. The amelioration of the effects of an inhibitory aldehyde byproduct of the reaction process by means of its formation of an adduct with an agent provided in the aqueous reaction phase is also an aspect of the present invention. Moreover, selected organic solutions of the optically active glycidic ester intermediates have been developed which are particularly useful in subsequent processes involving the isolation of the intermediate directly from the solution or use of the solution to introduce a new reagent for a further chemical transformation. Alternative production routes to diltiazem utilize o-aminothiophenol in place of o-nitrothiophenol in the step involving opening of and addition to the oxirane ring (S. Nagao et al., U.S. Pat. No. 4,416,819). Such alternative processes also utilize methyl trans-3-(4-methoxyphenyl)glycidate as an intermediate, and thus are subject to improvement by the process of the present invention. It is known that the above pharmacological effects reside in only one of the two enantiomers of the diltiazem, namely, the d-enantiomer (Merck Index, 10th Edition, 1986, p. 466; Physician's Desk Reference, 41st Edition, 1987, p. 1173). Thus, there is a need to produce diltiazem with the correct stereochemistry, and to introduce such correct stereochemistry at an efficient point in the overall synthesis by production of an optically purified and stereochemically correct intermediate or precursor. As discussed above, diltiazem can be produced from a 3-(4-methoxyphenyl)glycidic acid ester intermediate. At the present time, this intermediate is used in its racemic form, i.e., it is not optically active. Web site: http://www.delphion.com/details?pn=US06521445__ •

Process for the preparation of (2RS,3RS)-3-(2'-aminophenylthio)-2-hydroxy-3-(4"methoxyphenyl)-propioni c acid methyl ester Inventor(s): Fiege; Helmut (Leverkusen, DE), Hagedorn; Ferdinand (Leverkusen, DE) Assignee(s): Bayer Aktiengesellschaft (Leverkusen, DE) Patent Number: 5,756,809 Date filed: November 1, 1996 Abstract: (2RS,3RS)-3-(2'-aminophenylthio)-2-hydroxy-3-(4"-methoxyphenyl)-propionic acid methyl ester, an important precursor for the preparation of the pharmaceutical active substance diltiazem, is obtained in a particularly high stereoselectivity and yield by addition of o-aminothiophenol onto 3-(4'-methoxyphenyl)-glycidic acid methyl ester

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if the reaction is carried out in the presence of alkali metal salts of weak acids in the presence of catalytic amounts of iron compounds. Excerpt(s): The present invention relates to an improved process for the preparation of (2RS,3RS)-3-(2'-aminophenylthio)-2-hydroxy-3-(4"-methoxyphenyl)-propionic acid methyl ester (also called AHMPE below) by selective addition of o-aminothiophenol onto 3-(4'-methoxyphenyl)-glycidic acid methyl ester (also called MPG ester below). It is known to prepare AHMPE by addition of unsubstituted o-aminothiophenol onto MPG ester in a non-polar solvent and at elevated temperature. AHMPE is a precursor for the pharmaceutical active compound diltiazem (cf. Chem. Pharm. Bull. 18, 2028 (1970)). European Laid-Open Specification 609 031 describes a process in which the addition of o-aminoalkylamino-thiophenol onto MPG ester to give the threo form of the ester adduct is carried out in the presence of di- or trivalent iron ions. Web site: http://www.delphion.com/details?pn=US05756809__ •

Process for the pulsatile delivery of diltiazem HCL and product produced thereby Inventor(s): Sharma; Vinay K. (Long Valley, NJ) Assignee(s): Wockhardt Europe Limited (Dublin II, IE) Patent Number: 5,914,134 Date filed: January 27, 1997 Abstract: A drug delivery system for diltiazem-HCl comprises:a blend of fast, medium and slow release fractions of a multi-layered diltiazem bead substrate, the fast release fraction comprised of a diltiazem bead substrate layered with a polymeric membrane coating having a membrane coating weight gain of from 14 to 18 percent, the medium release fraction comprised of a diltiazem bead substrate layered with a polymeric membrane coating having a membrane coating weight gain of from 39 to 43 percent, and the slow release fraction comprised of diltiazem bead substrate layered with polymeric membrane coating having a membrane coating weight gain of from 63 to 67 percent, wherein at least one of the polymeric membrane coatings comprises a waterinsoluble, slightly permeable polymer and a plasticizer triethyl citrate. Excerpt(s): The present invention relates to a drug delivery system, and, more particularly, to a pulsatile drug delivery system for diltiazem HCl capable of sitespecific delivery and pulsatile (bolus) kinetics. Several investigators have developed pulsatile drug delivery systems that provide slow and/or fast release of a drug based upon physical conditions such as pH, temperature, ionic strength, glucose concentration of metabolites (U.S. Pat. No. 5,226,902); use expandable core material that can be released at specific sites over a period of time (U.S. Pat. No. 4,649,043); or employ an orificed wall constructed of an elastomer that stretches under pressure as osmotic infusion progresses (U.S. Pat. No. 5,221,278). Still others report that, by varying the thickness of the film, drug release after the lag period can be enhanced by electrostatic or other physiochemical interactions between the polymer and organic acids. Web site: http://www.delphion.com/details?pn=US05914134__

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Use of diltiazem for treating retinal pathologies Inventor(s): Dreyfus; Henri (Strasbourg, FR), Frasson; Maria (Rouffach, FR), Picaud; Serge (Strasbourg, FR), Sahel; Jose (Strasbourg, FR) Assignee(s): INSERM (Institut National de la Sante et de la Recherche Medicale) (Paris, Cedex, FR), Universite Louis Pasteur (Strasbourg, FR) Patent Number: 6,716,835 Date filed: June 8, 2001 Abstract: The invention concerns the use of a calcium channel blocker compound and/or cyclic GMP-dependent channels, namely diltiazem, for treating retinal pathologies, and more particularly retinal diseases caused by degeneration of visual receptors, in a human or animal. Excerpt(s): The present invention concerns the use of blocker compounds of calcium channels and/or channels activated by 3'5' cyclic guanosine monophosphate (cGMP), in the field of treating retinal pathologies, and more particularly retinal diseases resulting from photoreceptor degeneration, in humans or animals, such as retinitis pigmentosa or other pathologies substantially involving the photoreceptors, especially age-related macular degeneration. Retinitis pigmentosa designates a group of these degenerative diseases of the photoreceptors (Berson, 1996) leading to blindness. Numerous mutations affecting various rod proteins, and potentially the cause of this disease, have been described. Among these mutations can be mentioned those affecting the genes of proteins implicated in the phototransduction cascade, such as rhodopsin, transducin, phosphodiesterase, arrestin, or structural proteins such as peripherin. Web site: http://www.delphion.com/details?pn=US06716835__

Patent Applications on Diltiazem 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 diltiazem: •

Composition for pulsatile delivery of diltiazem and process of manufacture Inventor(s): Hussain, Javed; (Maharashtra, IN), Khorakiwala, Habil F.; (Mumbai, IN), Sharma, Vinay K.; (Long Valley, NJ) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030003149 Date filed: April 12, 2001 Abstract: A once-a-day controlled release drug delivery system of diltiazem hydrochloride is provided, which is bioequivalent in plasma profile of Cardizem CD. The fast, medium, and slow release fractions are prepared using various compositions and weight gains. The individual fill weights are computed and then are filled into the same capsule using specialized encapsulation equipment using a triple-filling process. A

9

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

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preferred membrane dispersion that is used for preparing the fast release fraction contains 0.2% of sodium lauryl sulfate along with 20% of water soluble plasticizer (triethyl citrate), and 2% silicone dioxide, based on quaternary polymethacrylate on the weight basis. This combination provides an initial pulsatile burst after a lag time of 2 hours, leading to in-vivo bioequivalence. The preferred membrane dispersion that is used for preparing the medium release and the slow release fractions contain 16% of water soluble plasticizer along with 5% silicone dioxide, based on quaternary polymethacrylate. This combination provides an optimal glass transition temperature that allows for the preparation of exceptionally increased weight gains. Additionally, it provides targeted input of drug release for achieving bioequivalence. Regardless of significant in-vitro inequivalence to the release rate profile of the innovator product, the in vivo-equivalence data comply with required regulatory guidelines. Excerpt(s): This application is a claims priority from U.S. provisional patent application Ser. No. 60/___ , ___, which was filed on filed Apr. 12, 2000 as U.S. patent application Ser. No. 09/547,838, for which a petition under 37 C.F.R.sctn.1.53(c) to convert the nonprovisional application to a provisional application was filed on Aug. 29, 2000, which is incorporated herein by reference. A three-pellet, pulsatile drug delivery system results in bioequivalence to Cardizem.RTM. CD. The fast release membrane (FRF) composition includes an anionic surface active agent which assures complete drug release after providing a desired lag time. The medium release fraction (MRF) and the slow release fraction (SRF) are plasticized with decreased concentrations of triethyl citrate and increased concentrations of silicone dioxide powder for improved process performance. Diltiazem is a benzothiazine derivative possessing calcium antagonist activity. Diltiazem blocks the influx of calcium ions in smooth and cardiac muscle and thus exerts potent cardiovascular effects. Diltiazem has been shown to be useful in alleviating symptoms of chronic heart disease, particularly angina pectoris and myocardial ischemia and hypertension, while displaying a low incidence of side effects. The first dosage forms of diltiazem sold in the United States were tablets containing 30 mg or 60 mg of diltiazem hydrochloride sold under the tradename Cardizem.RTM. by Marion Laboratories Inc. Single oral doses of 30 mg and to 120 mg of Cardizem.RTM. tablets result in peak plasma levels about 2 to 3 hours after ingestion, and the elimination half-life is about 3 to 5 hours. Because of the relatively rapid absorption of diltiazem hydrochloride from such tablets and rapid elimination, the usual dosage regimen for immediate release tablets is for a dose to be taken three or four times daily. The need for such frequent administration may reduce patient compliance. Thus adverse therapeutic effects can arise. It thus became apparent that it would be preferable to administer diltiazem hydrochloride in a dosage form that releases the diltiazem hydrochloride much more slowly than Cardizem.RTM. tablets, so as to enable the frequency of ingestion by the patient to be reduced to once daily. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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DILTIAZEM CONTROLLED RELEASE FORMULATION AND METHOD OF MANUFACTURE Inventor(s): CHEN, CHIH-MING; (DAVIE, FL), CHENG, XIU XIU; (DAVIE, FL), JAN, STEVE; (CORAL SPRINGS, FL) Correspondence: Hedman Gibson & Costigan; 1185 Avenue OF The Americas; New York; NY; 100362601 Patent Application Number: 20010007681 Date filed: July 20, 1998 Abstract: A controlled release diltiazem dosage formulation comprising a plurality of active pellets coated with an extended release coating wherein the active pellets contain diltiazem or a pharmaceutically acceptable salt, a pharmaceutically acceptable inert seed and a binder and the extended release coating contains a water insoluble water permeable polymer, a channeling agent, a lubricant and optionally a surfactant. A single batch intermittent method of manufacturing a heterogeneous population of extended release pellets for use as a dosage formulation is also disclosed. Excerpt(s): The present invention relates to a controlled release formulation for the drug diltiazem or its pharmaceutically acceptable salts thereof and a method for manufacturing a controlled release dosage formulation containing diltiazem or a pharmaceutically acceptable salt thereof as the active ingredient. Diltiazem hydrochloride, commonly referred to as diltiazem, is a benzothiazine derivative that blocks the influx of calcium ions in smooth and cardiac muscle and has few side effects. Diltiazem has been shown to be useful in alleviating symptoms of chronic heart disease, particularly angina pectoris, myocardial ischemia and hypertension. Diltiazem also has been shown to have activity against arrythmia and may be useful in treating congestive cardiac insufficiency, Raynaud's syndrome and peripheral and cerebral circulatory insufficiency. Diltiazem is sold commercially in extended release pharmaceutical dosage forms that attempt to maintain a therapeutic serum level of diltiazem and minimize the effects of missed doses of the drug caused by lack of patient compliance. One commercial form of extended release diltiazem is Cardizem CD.RTM.). Cardizem CD.RTM. is described as a once-a-day extended release capsule containing diltiazem HCl and fumaric acid. In the prosecution history of U.S. Pat. No. 5,286,497, representations were made that the formulation disclosed in that patent is the formulation for Cardizem CD.RTM. The formulation for Cardizem CD.RTM. is identified in the prosecution history of U.S. Pat. No. 5,286,497 as having a "stair step release profile" that is created by a blend of two types of beads referred to as a rapid release bead and an extended release bead. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Extended release formulation of diltiazem hydrochloride Inventor(s): Lippa, Arnold; (Ridgewood, NJ) Correspondence: Shahan ISLAM,ESQ.; Rosenman & Colin Llp; 575 Madison Avenue; New York; NY; 10022-2585; US Patent Application Number: 20020172694 Date filed: May 15, 2001

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Abstract: An extended release formulation of diltiazem which is suitable for once-daily oral administration comprises a quantity of a quick release preparation of diltiazem or a pharmaceutically active salt thereof, mixed with a quantity of a slow release (or delayed release) preparation of diltiazem or a pharmaceutically active salt thereof. The quick release preparation used obtains a maximal release of diltiazem within approximately 12 hours after administration, and then falls toward baseline levels. The delayed release preparation individually shows a maximal release of diltiazem at between approximately 6-8 hours after administration. The formulation containing the two preparation achieves a maximal release of diltiazem approximately within 1-2 hours after administration, and the levels of released diltiazem remain near these maximal levels for approximately another 12 hours after administration, compared to other extended release formulations of diltiazem (referred to herein as slow or delayed release preparations) which achieve maximal release approximately 9 hours after oral administration. The preferred embodiment is a capsule containing the formulation, which, based upon the total quantity of drug in the formulation rather than total weight of the formulation, comprises equal weights of the quick release and slow release forms of diltiazem, and preferably up to 50 percent by weight of each of the slow (or delayed) and quick release preparation of diltiazem. The present invention has application for combinations of other preparations of quick release and slow or delayed release pharmaceuticals. Excerpt(s): This invention relates to a formulation of diltiazem hydrochloride. In particular, this invention is an extended release formulation of diltiazem hydrochloride that is suitable for once daily use and which more rapidly achieves a maximum therapeutic level of diltiazem hydrochloride than that obtained with currently available formulations. ((25-cis-3-(Acetoxyl)-5-[2-(dimethylamino)ethyl]-2-3-dihydro-2-(4-methoxyph enyl)-1,5-benzothiazepin-4(5H)-one) is a safe and effective treatment for hypertension and both stable and unstable angina pectoris (1). A variety of formulations containing diltiazem or diltiazem hydrochloride are available, as will be described below. These formulations provide a range of dose regimens, ranging from dosing as often as four times daily ("q.i.d."); twice daily ("b.i.d."), such as approximately every 12 hour, or once-daily ("q.d."). Patient compliance with the dosing regimens has been a factor in the development of the sustained or extended release formulations, enabling the twice-daily or once-daily dosing. CARDIZEM CD (TM) is a once-a-day extended release formulation of diltiazem hydrochloride sold by Bovail and which is prescribed for treatment of hypertension and angina (2). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Injectable pharmaceutical composition for treatment and reversal of erectile dysfunction Inventor(s): Lin, An-Hao; (West Covina, CA) Correspondence: John Kappos; 3404 East Woodbine Road; Orange; CA; 92867; US Patent Application Number: 20010014685 Date filed: March 2, 2001 Abstract: An injectable pharmaceutical composition for treatment of erectile dysfunction. The composition includes prostaglandin E-1, and optionally further includes levsin and/or additional vasodilators such as diltiazem HCl, verapamil, chlorpromazine, d,L-hyoscyamine, and 6,7-dimethoxy-1-veratrylisoquinoline HCl. The composition is effective for long-term restoration of normal erectile function to a patient

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having erectile dysfunction. The ability to reverse erectile dysfunction may be further enhanced by the inclusion of vitamin B-6, B-12, folic acid, and/or TPA. Also disclosed are methods for treatment and reversal of erectile dysfunction by injecting the pharmaceutical composition into the penis, either by subcutaneous or intracavernosal injection. Excerpt(s): This is a continuation of U.S. application Ser. No. 09/321,693, filed May 28, 1999, which is a continuation-in-part of U.S. application Ser. No. 09/110,814, filed Jul. 6, 1998, which is a continuation-in-part of U.S. application Ser. No. 09/007,166, filed Jan. 14, 1998. This application is also a continuation-in-part of U.S. application Ser. No. 09/007,142, filed Jan. 14, 1998. The contents of all of the above applications are incorporated herein by reference. The present invention relates to pharmaceutical compositions for treatment of erectile dysfunction. The invention also relates to methods of administering the compositions for treatment of erectile dysfunction, including by subcutaneous (sub-q), intramuscular (IM), intracavernosal (IC), intravenous (IV), and intraarterial injection. The invention further relates to methods for reversal of erectile dysfunction by administering the compositions disclosed herein to a patient in order to improve penile circulation, which has the long-term benefit of restoring erectile function well after administration of the compositions of the invention. Erectile dysfunction is a serious condition which afflicts a significant percentage of the male population worldwide. This condition often has significant psychological effects which can, in severe cases, significantly reduce the quality of life for the person affected. The effects are often most severe among elderly male patients, but this condition has become increasingly prevalent within the middle-aged, and even the youthful segments of the male population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Osmotic device containing diltiazem and an ACE inhibitor or diuretic Inventor(s): Faour, Joaquina; (Buenos Aires, AR), Vergez, Juan A.; (Buenos Aires, AR) Correspondence: Innovar, Llc; P O Box 250647; Plano; TX; 75025; US Patent Application Number: 20020006430 Date filed: January 5, 2001 Abstract: The present invention provides an osmotic device containing controlled release diltiazem in the core in combination with a rapid release ACE inhibitor, or diuretic, in an external coat. The delivery device of the invention can also be a chronotherapeutic osmotic device that provides a delayed and controlled release of diltiazem and a delay and rapid release of an ACE inhibitor or diuretic. A wide range of ACE inhibitors or diuretics can be used in this device. Particular embodiments of the invention provide osmotic devices having predetermined release profiles. One specific embodiment of the osmotic device includes an external coat that has been spray coated rather than compression coated onto the device. The device with spray coated external core is smaller and easier to swallow than the similar device having a compression coated external coat. The device is useful for the treatment of blood pressure or hypertension related disorders. Excerpt(s): The present application claims the priority of U.S. provisional application for patent Ser. No. 60/176,174 filed Jan. 13, 2000. This invention pertains to an osmotic device containing diltiazem and an angiotensin converting enzyme (ACE) inhibitor. More particularly, it pertains to an osmotic device tablet which provides a controlled

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release of diltiazem and a rapid or immediate release of an ACE inhibitor diuretic compound. ACE inhibitors, diuretics and calcium channel blockers are three types of antihypertensive agents used either as monotherapy or in combination to regulate blood pressure in the treatment of hypertension. The efficacy of ACE inhibitors is related to the initial level of plasma angiotensin II (Ang II) or plasma renin activity. However, patients with low plasma renin activity also experience a fall in blood pressure during ACE inhibitor therapy. In contrast to diuretics, diltiazem does not have adverse metabolic effects on electrolytes, carbohydrate metabolism and lipid metabolism. Diltiazem is particularly indicated in patients with hypertension and concurrent angina pectoris, diabetes, hyperlipidemias and chronic renal disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for preparing diltiazem using a heterogeneous trifunctional catalyst Inventor(s): Choudary, Boyapati M.; (Andhra Pradesh, IN), Chowdari, Naidu S.; (Andhra Pradesh, IN), Madhi, Sateesh; (Andhra, IN), Mannepalli, Lakshmi K.; (Andhra Pradesh, IN) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20040127704 Date filed: December 31, 2002 Abstract: The present invention comprises a simplified synthesis of (+)-diltiazem through IE-PdOsW wherein IE is ion-exchanger, catalyzed three-component coupling reaction and Fe.sup.3+-exchanged clay catalyzed ring opening of sulfite with 2aminothiophenol followed by cyclization as key steps. Excerpt(s): The present invention relates to an improved process for the preparation of diltiazem by first synthesizing (2R,3S)-(-)-Ethyl-2,3-dihydroxy-3-(4methoxyphenyl)propionate with greater than 99% enantioselectivity and devoid of osmium even in the crude in a single pot using recyclable multifunctional catalysts of the formula IE-IE-PdOsW, in which IE is a ion-exchanger comprising LDH, quaternary ammonium salt anchored on silica, clay, alumina, magnesia or resin, converting the diol obtained without further crystallization into cyclic sulfite and reacting the cyclic sulfite with 2-aminothiophenol in the presence of Fe.sup.3+-exchanged clay in xylene to obtain a cyclic lactam which is then subjected to N-alkylation and acylation to provide diltiazem. Diltiazem, a typical calcium antagonist, has been used throughout the world as a remedy for angina and hypertension. Among the four possible stereoisomers of diltiazem, only the (+)-(2S,3S)-isomer exhibits potent coronary vasodilating activity. Therefore, diltiazem has been developed and marketed as a single isomer. For the synthesis of diltiazem, many processes have been extensively investigated and at present it is mainly manufactured by the route using the optically active (-)-trans methyl glycidate as a key intermediate, which is prepared via enzymatic methods. However, there is an inherent drawback to the optical resolution in that the maximum yield of one enantiomer cannot exceed 50%. Although several approaches for the asymmetric synthesis of diltiazem have been reported, for reasons involving enantiomeric purity and overall efficiency, a more efficient method is needed. Reference is made to U.S. Pat. No. 5,869,697, (1999) wherein synthesis of diltiazem was carried using optically pure chiral diols. The inherent disadvantage is the optically pure diols used are expensive involving tedious experimental procedures. Reference is also made to U.S. Pat. No. 6,180,785 (2001) wherein synthesis of diltiazem was carried by using optically pure

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chiral diols. The inherent disadvantage is the optically pure diols used are expensive involving tedious experimental procedures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Sustained-release microgranules containing diltiazem as active principle Inventor(s): Debregeas, Patrice; (Paris, FR), Leduc, Gerard; (Malesherbes, FR), Oury, Pascal; (Paris, FR), Suplie, Pascal; (Montaure, FR) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20020182253 Date filed: December 3, 2001 Abstract: Novel forms of sustained-release microgranules (LP) containing diltiazem are disclosed. The microgranules consist of a neutral granular carrier coated with an active layer including diltiazem or a pharmaceutically acceptable salt thereof as the active principle, a surfactant and a binder, and an outer layer providing sustained release of the active principle (layer LP). Excerpt(s): The present invention relates to novel forms of sustained-release (SR) microgranules containing Diltiazem as active principle. Diltiazem is a calciumantagonist benzothiazepine derivative which is useful for the treatment of arterial hypertension. It may be administered in various forms: tablets, injectable solutions or gelatin capsules containing sustained-release granules. The latter have the advantage of allowing the administration to be taken as a single dose required for daily treatment. Various forms of Diltiazem SR microgranules have been described in the prior art, the most advantageous being that described in patent application EP-A-0,149,920, comprising a core combining Diltiazem with a water-soluble organic acid, in particular fumaric acid. The reason for this is that Diltiazem, or its pharmaceutically acceptable salts, are sparingly soluble at neutral or basic pH, and the presence of a water-soluble organic acid has proven to be particularly important, making it possible to create a buffered acidic microenvironment, promoting both the dilution and the absorption of the Diltiazem in areas of the digestive tract where the pH is too high. It has, nevertheless, been observed that for these SR forms, the solubilization and absorption of Diltiazem were dependent on the absorption of food, and are different when uptake of the microgranules is carried out on an empty stomach or during meals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Topical pharmaceutical composition comprising a cholinergic agent or a calcium channel blocker Inventor(s): Kamm, Michael A.; (London, GB), Phillips, Robin K.S.; (Northwood, GB) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040028752 Date filed: August 8, 2002 Abstract: A method and composition are provided for the treatment of an anorectal disorder and for controlling the pain associated therewith. The method comprises

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administering to a subject in need of such treatment therapeutically effective amounts of a calcium channel blocker either alone or together with a nitric oxide donor. Amlodipine, anipamil, barnidipine, benidipine, bepridil, darodipine, diltiazem, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, lidoflazine, manidipine, mepirodipine, nicardipine, nifedipine, niludipine, nilvadipine, nimodipine, nisoldipine, nitrendipine, perhexiline, tiapamil, verapamil and pharmaceutically acceptable salts thereof, are suitable calcium channel blockers. Excerpt(s): This invention relates to the use of a calcium channel blocker or a cholinegic agent, particularly diltiazem and bethanechol, alone and in combination for the treatment of benign anal diseases where there is an associated anal sphincter spasm. The invention particularly relates to the treatment of anal fissures and painful haemorrhoidal conditions. A fissure is a split in the skin of the distal anal canal. It is a common complaint in young adults with a roughly equal incidence in both sexes. Acute fissures are very common and most heal spontaneously, but a proportion progress to form a chronic linear ulcer in the anal canal and show great reluctance to heal without intervention. Treatment has remained largely unchanged for over 150 years and the pathogenesis of anal fissure is not fully understood. The passage of a hard stool bolus has traditionally been thought to cause anal fissure. Thus for acute fissures the avoidance of constipation, such as involving a high bran diet, has been used as treatment for many years. 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 diltiazem, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “diltiazem” (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 diltiazem. You can also use this procedure to view pending patent applications concerning diltiazem. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “diltiazem” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •

Calciumantagonisme en myocardischemie: Nederlands Diltiazem Symposium, 22 november 1986, Slot Zeist. Author: editors, P.G. Hugenholtz en P.A. van Zwieten; Year: 1987

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New drug therapy with a calcium antagonist: Diltiazem Hakone Symposium '78. Author: editor, Richard J. Bing; Year: 1979

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Preclinical and clinical aspects on calcium entry blockers with special emphasis on diltiazem in the treatment of angina pectoris: proceedings from the First Nordic Cardizem (Diltiazem) Workshop in Malmö, Sweden, March 1-2, 1984. Author: editors, Karl-Erik And; Year: 1985

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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

Controversial Therapies Source: in Manu, P. Pharmacotherapy of Common Functional Syndromes: EvidenceBased Guidelines for Primary Care Practice. Binghamton, NY: Haworth Medical Press. 2000. p. 131-152. Contact: Available from Haworth Medical Press, an imprint of Haworth Press, Inc. 10 Alice Street, Binghamton, New York 13904-1580. (800) HAWORTH or (800) 429-6784. Outside United States and Canada (607) 722-5857. Fax (800) 895-0582. E-mail: [email protected]. Website: www.haworthpressinc.com. PRICE: $69.95 plus shipping and handling. ISBN: 0789005883. Summary: This chapter is from a book that evaluates drug therapies for each of the four major functional disorders: chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome (IBS), and premenstrual syndrome. In this chapter, the third of six short chapters that focus on IBS, the author introduces and reviews controversial drug therapies used for the condition. The author focuses on bulking agents, including ispaghula husk, psyllium, and calcium polycarbophil; smooth muscle relaxants, including dicyclomine hydrochloride, mebeverine, trimebutine, and octylonium bromide; calcium channel blocking agents, including diltiazem, pinaverium, and cisapride (recently found to be associated with heart rhythm abnormalities). The author discusses some of the basic research on each drug's use in patients with IBS. Treatment with ispaghula was no better than placebo with regard to the principal symptoms of abdominal pain, abdominal distention, and the presence of frequent bowel movements; subjective improvement was noted by the patients, however. An eight week study of treatment with psyllium noted an improvement in the severity of abdominal pain and the number of normal stools in both treatment groups (drug and placebo groups) as compared with baseline; there was no difference between placebo and psyllium in the proportion of patients who considered themselves 'much better' after treatment. In the study of calcium polycarbophil, there were no statistically significant differences between the active agent and placebo as measured by global scores, by the specific symptom scores for abdominal pain, abdominal distention, nausea, and stool consistency, or by the proportion of patients who favored one of the treatments over the other. In studies of dicyclomine, 94 percent of patients treated with the drug improved (compared with 54 percent of those who took placebo). Mebeverine, widely used in the United Kingdom to treat IBS, fared no better than placebo for symptom relief. Treatment with 200 mg of trimebutine three times daily was considered superior to placebo, based primarily on patient preference for the drug; however, side effects at clinical dosage levels remain problematic. Octylonium bromide resulted in a slight statistical advantage over placebo (65 percent improvement compared with 50 percent improvement, respectively). Diltiazem appeared to be slightly more effective than placebo when it was the first treatment used in the crossover sequence of the trial, but the overall outcome

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after nine weeks indicated no meaningful advantage. Of the two calcium channel blocking agents tested in clinical trials, pinaverium but not diltiazem appears to offer short term benefit.

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

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

Combination of low-dose diltiazem and trimetazidine effective for angina Source: Reuters Industry Breifing Date: March 21, 2003

•

Amiodarone as effective as diltiazem in controlling atrial tachyarrhythmias Source: Reuters Medical News Date: July 06, 2001

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•

FTC not planning to fine Andrx over diltiazem agreement; shares rise Source: Reuters Medical News Date: March 17, 2000

•

Court dismisses Biovail's diltiazem suit Source: Reuters Medical News Date: January 14, 2000

•

FDA approves generic diltiazem injection Source: Reuters Medical News Date: May 11, 1999

•

IV diltiazem with t-PA prevents ischemia after AMI Source: Reuters Medical News Date: September 21, 1998

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IV diltiazem for unstable angina improves long-term prognosis Source: Reuters Medical News Date: August 20, 1998

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Andrx's diltiazem hydrochloride capsules get FDA approval Source: Reuters Medical News Date: July 13, 1998

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FDA approves Akorn's diltiazem HCl injection Source: Reuters Medical News Date: May 13, 1998

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Once Daily Diltiazem Effective For Patients With Stable Angina Pectoris Source: Reuters Medical News Date: February 26, 1998

•

Forest Labs Gets FDA Approval Of Diltiazem For Chronic Stable Angina Source: Reuters Medical News Date: February 04, 1998

•

Intracoronary Diltiazem At Onset Of MI Reduces Infarct Size In Animals Source: Reuters Medical News Date: April 08, 1997

•

IV Diltiazem Superior to Glyceryl Trinitrate For Patients With Unstable Angina Source: Reuters Medical News Date: December 25, 1995

•

Once-Daily Doses Of Diltiazem Effective As Antianginal Therapy Source: Reuters Medical News Date: March 29, 1995 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.

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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 “diltiazem” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “diltiazem” (or synonyms). If you know the name of a company that is relevant to diltiazem, 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 “diltiazem” (or synonyms).

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

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

Systemic - U.S. Brands: Adalat; Adalat CC; Calan; Calan SR; Cardene; Cardizem; Cardizem CD; Cardizem SR; Dilacor-XR; DynaCirc; Isoptin; Isoptin SR; Nimotop; Norvasc; Plendil; Procardia; Procardia XL; Vascor; Verelan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202107.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

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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

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•

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

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

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

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

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

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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

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •

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

•

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

•

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

•

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

•

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

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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

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

•

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

•

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

12

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “diltiazem” (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 8283 9 892 3 33 9220

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “diltiazem” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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

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

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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

19 Adapted 20

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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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 diltiazem 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 diltiazem. 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 diltiazem. 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 “diltiazem”:

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Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Herbal Medicine http://www.nlm.nih.gov/medlineplus/herbalmedicine.html Migraine http://www.nlm.nih.gov/medlineplus/migraine.html Pulmonary Hypertension http://www.nlm.nih.gov/medlineplus/pulmonaryhypertension.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 diltiazem. 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 diltiazem. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with diltiazem. 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 diltiazem. 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 “diltiazem” (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 “diltiazem”. 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 “diltiazem” (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 “diltiazem” (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.22

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

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

22

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

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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)23: •

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

•

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

•

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

•

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

•

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

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

23

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

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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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DILTIAZEM 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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Actin: Essential component of the cell skeleton. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [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] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU]

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Adduct: Complex formed when a carcinogen combines with DNA or a protein. [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] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring

Dictionary 127

substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alfentanil: A short-acting opioid anesthetic and analgesic derivative of fentanyl. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients. [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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH]

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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] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anal Fissure: A small tear in the anus that may cause itching, pain, or bleeding. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH]

Dictionary 129

Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH]

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Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [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] Antiproliferative: Counteracting a process of proliferation. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [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] Aqueous: Having to do with water. [NIH]

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Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [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] Aspartate: A synthetic amino acid. [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] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [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] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] 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] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auscultation: Act of listening for sounds within the body. [NIH]

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Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] 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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Bepridil: Beta-((2-Methylpropoxy)methyl)-N-phenyl-N-(phenylmethyl)-1pyrrolidineethanamine. A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Bethanechol: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, cardiac rate changes, and bronchial spasms. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] 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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific

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combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioequivalent: Having the same strength and similar bioavailability in the same dosage form as another specimen of a given drug substance. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [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]

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Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] 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 blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Spasm: Spasmodic contraction of the smooth muscle of the bronchi. [NIH] Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulking Agents: Laxatives that make bowel movements soft and easy to pass. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [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] Calcium blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH]

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Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] 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] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU]

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Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Abnormalities: Congenital structural abnormalities of the cardiovascular system. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Celiprolol: A cardioselective beta-1-adrenergic antagonist that may act as a partial agonist at some adrenergic sites. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing

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specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] 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] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [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

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characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] 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] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU]

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Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [NIH] Colitis: Inflammation of the colon. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the

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standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Comprehensive Health Care: Providing for the full range of personal health services for diagnosis, treatment, follow-up and rehabilitation of patients. [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] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone cells: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

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Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [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 Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] 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 Circulation: The circulation of blood through the coronary vessels of the heart. [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] Corpus: The body of the uterus. [NIH] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]

Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH]

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Cystitis: Inflammation of the urinary bladder. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dantrolene: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH]

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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] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [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]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during cryopreservation. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discriminant Analysis: A statistical analytic technique used with discrete dependent variables, concerned with separating sets of observed values and allocating new values. It is sometimes used instead of regression analysis. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important

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determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Doxazosin: A selective alpha-1-adrenergic blocker that lowers serum cholesterol. It is also effective in the treatment of hypertension. [NIH] Drip: The continuous slow introduction of a fluid containing nutrients or drugs. [NIH] Drug Combinations: Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. It is differentiated from

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combination drug therapy in which two or more drugs are administered separately for a combined effect. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH]

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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [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] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic

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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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [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] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extracorporeal: Situated or occurring outside the body. [EU]

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Extracorporeal Membrane Oxygenation: Application of a life support system that circulates the blood through an oxygenating system, which may consist of a pump, a membrane oxygenator, and a heat exchanger. Examples of its use are to assist victims of smoke inhalation injury, respiratory failure, and cardiac failure. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] 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] Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] 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] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Foetoplacental: Pertaining to the fetus and placenta. [EU] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [NIH] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of

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action and is used in edema and chronic renal insufficiency. [NIH] Galenical: 1. Usually cap: of or relating to Galen or his medical principles or method. 2. Constituting a galenical. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallopamil: Coronary vasodilator that is an analog of iproveratril (verapamil) with one more methoxy group on the benzene ring. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

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

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic

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(drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

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] 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] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Murmurs: Abnormal heart sounds heard during auscultation caused by alterations in the flow of blood into a chamber, through a valve, or by a valve opening or closing abnormally. They are classified by the time of occurrence during the cardiac cycle, the duration, and the intensity of the sound on a scale of I to V. [NIH] Heart Sounds: The sounds heard over the cardiac region produced by the functioning of the heart. There are four distinct sounds: the first occurs at the beginning of systole and is heard as a "lubb" sound; the second is produced by the closing of the aortic and pulmonary valves

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and is heard as a "dupp" sound; the third is produced by vibrations of the ventricular walls when suddenly distended by the rush of blood from the atria; and the fourth is produced by atrial contraction and ventricular filling but is rarely audible in the normal heart. The physiological concept of heart sounds is differentiated from the pathological heart murmurs. [NIH]

Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Hospital Charges: The prices a hospital sets for its services. Hospital costs (the direct and indirect expenses incurred by the hospital in providing the services) are one factor in the determination of hospital charges. Other factors may include, for example, profits, competition, and the necessity of recouping the costs of uncompensated care. [NIH] Hospital Costs: The expenses incurred by a hospital in providing care. The hospital costs attributed to a particular patient care episode include the direct costs plus an appropriate proportion of the overhead for administration, personnel, building maintenance, equipment, etc. Hospital costs are one of the factors which determine hospital charges (the price the hospital sets for its services). [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hydration: Combining with water. [NIH]

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Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypoxic: Having too little oxygen. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileus: Obstruction of the intestines. [EU] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunogenic: Producing immunity; evoking an immune response. [EU] Immunology: The study of the body's immune system. [NIH] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is

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inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] 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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indapamide: A sulfamyl diuretic with about 16x the effect of furosemide. It has also been shown to be an effective antihypertensive agent in the clinic. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infections: The illnesses caused by an organism that usually does not cause disease in a person with a normal immune system. [NIH]

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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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques.

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[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] Iron Compounds: Inorganic compounds that contain iron as an integral part of the molecule. [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] Isosorbide Dinitrate: A vasodilator used in the treatment of angina. Its actions are similar to nitroglycerin but with a slower onset of action. [NIH] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Lactation: The period of the secretion of milk. [EU]

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Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Leg Ulcer: Ulceration of the skin and underlying structures of the lower extremity. About 90% of the cases are due to venous insufficiency (varicose ulcer), 5% to arterial disease, and the remaining 5% to other causes. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Lidoflazine: Coronary vasodilator with some antiarrhythmic action. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] 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] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH]

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Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] 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] Lubricants: Oily or slippery substances. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manic: Affected with mania. [EU]

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Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Potentials: Ratio of inside versus outside concentration of potassium, sodium, chloride and other ions in diffusible tissues or cells. Also called transmembrane and resting potentials, they are measured by recording electrophysiologic responses in voltagedependent ionic channels of (e.g.) nerve, muscle and blood cells as well as artificial membranes. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] 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] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH]

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Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits Guanylate cyclase, and has been used to treat cyanide poisoning and to lower levels of methemoglobin. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] Mibefradil: A benzimidazoyl-substituted tetraline that binds selectively to and inhibits calcium channels, T-type. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Miscible: Susceptible of being mixed. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration,

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pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] 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] 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

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known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [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] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Netilmicin: Semisynthetic 1-N-ethyl derivative of sisomycin, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH]

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Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH] Nicorandil: A derivative of the niacinamide that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nisoldipine: 1,4-Dihydro-2,6-dimethyl-4 (2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-methylpropyl ester. Nisoldipine is a dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitrendipine: Ethyl methyl 2,4-dihydro-2,6-dimethyl-4(3-nitrophenyl)-3,5pyridinedicarboxylate. A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. [NIH]

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Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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]

Nitric-Oxide Synthase: An enzyme that catalyzes the conversion of L-arginine, NADPH, and oxygen to citrulline, nitric oxide, and NADP+. The enzyme found in brain, but not that induced in lung or liver by endotoxin, requires calcium. (From Enzyme Nomenclature, 1992) EC 1.14.13.39. [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] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Oestradiol: Growth hormone. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives

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and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [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)

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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]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [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] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] 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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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

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vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perhexiline: 2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis. [NIH] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Personal Health Services: Health care provided to individuals. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] 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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural

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substance acted upon. EC 2.4.1.1. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plasticizers: Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by

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the tissue reaction to its presence. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] 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] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of

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action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [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

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upon the rectum. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary congestion: Fluid accumulation in the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs,

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may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radial Artery: The direct continuation of the brachial trunk, originating at the bifurcation of the brachial artery opposite the neck of the radius. Its branches may be divided into three groups corresponding to the three regions in which the vessel is situated, the forearm, wrist, and hand. [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] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [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] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been

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recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] 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 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] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration

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(= cell respiration). [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Rhythmicity: Regular periodicity. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rod cells: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH]

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Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Sarcomere: The repeating structural unit of a striated muscle fiber. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] 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] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secular trends: A relatively long-term trend in a community or country. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] 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]

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Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] 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] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Smoke Inhalation Injury: Pulmonary injury following the breathing in of toxic smoke from burning materials such as plastics, synthetics, building materials, etc. This injury is the most frequent cause of death in burn patients. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

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

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Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmolytic: Checking spasms; antispasmodic. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sperm Motility: Ability of the spermatozoon to move by flagellate swimming. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermatozoon: The mature male germ cell. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [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] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenic Artery: The largest branch of the celiac trunk with distribution to the spleen,

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pancreas, stomach and greater omentum. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stridor: The loud, harsh, vibrating sound produced by partial obstruction of the larynx or trachea. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Succinylcholine: A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for. [NIH]

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Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces

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tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Talc: A native magnesium silicate. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] 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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] 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] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Timolol: A beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine and tremor. [NIH]

Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a

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heavy metal. [EU] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Traction: The act of pulling. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transducin: A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [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

Dictionary 181

primarily from fat in foods. [NIH] Trimebutine: Proposed spasmolytic with possible local anesthetic action used in gastrointestinal disorders. [NIH] Trimetazidine: A vasodilator used in angina of effort or ischemic heart disease. [NIH] Trivalent: Having a valence of three. [EU] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [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] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose Ulcer: Ulcer due to varicose veins. Chronic venous insufficiency in the deep veins of the legs leads to shunting the venous return into the superficial veins, in which pressure

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and flow rate, as well as oxygen content, are increased. [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] Vasculitis: Inflammation of a blood vessel. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]

Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] 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] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral

Dictionary 183

vision. [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] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Ziconotide: A drug used in the treatment of chronic pain. Also called SNX 111. [NIH]

185

INDEX A Abdomen, 125, 133, 134, 154, 156, 164, 165, 176, 177 Abdominal, 25, 96, 125, 132, 155, 158, 165, 168, 172 Abdominal Pain, 96, 125, 155 Acceptor, 125, 165 Acetaminophen, 77, 125 Acetone, 83, 125, 155 Acetylcholine, 27, 67, 125, 138, 157, 162, 163 Actin, 11, 37, 125, 161, 181 Acute lymphoblastic leukemia, 125 Acute lymphocytic leukemia, 68, 125 Acute renal, 36, 125 Acute tubular, 55, 125 Acylation, 72, 91, 125 Adaptability, 125, 136, 137 Adaptation, 125, 137, 162, 167 Adduct, 84, 85, 126 Adenosine, 126, 128, 166 Adipose Tissue, 126, 165 Adjunctive Therapy, 36, 126 Adjustment, 9, 125, 126 Adjuvant, 68, 80, 126 Adrenal Cortex, 126, 127, 141, 163 Adrenal Glands, 126, 172 Adrenal Medulla, 126, 136, 146, 163 Adrenergic, 4, 7, 32, 126, 127, 129, 130, 131, 136, 144, 146, 155, 157, 159, 169, 178, 179 Adrenergic beta-Antagonists, 126, 129 Adverse Effect, 20, 126, 175 Aerobic, 126, 147, 159 Affinity, 22, 66, 126, 142, 176 Agar, 126, 167 Agonist, 126, 132, 136, 144, 179 Albumin, 18, 127, 159, 167 Aldosterone, 12, 127 Alfentanil, 65, 127 Algorithms, 127, 133 Alkaline, 83, 127, 134, 179 Alkaloid, 67, 127 Alkalosis, 127, 179 Alkylation, 81, 82, 91, 127 Allergen, 127, 142 Allogeneic, 127, 150 Allografts, 56, 127

Alpha-1, 127, 144, 166 Alprenolol, 127, 159 Alternative medicine, 101, 127 Alternative Splicing, 8, 127, 170 Amino Acids, 128, 147, 165, 170, 180 Amiodarone, 15, 25, 26, 99, 128 Amlodipine, 4, 5, 14, 16, 28, 34, 39, 45, 93, 128 Amnestic, 128, 159 Anal, 14, 23, 48, 49, 50, 53, 93, 128, 143 Anal Fissure, 14, 23, 48, 49, 50, 53, 93, 128 Analgesic, 8, 125, 127, 128, 139, 156 Analog, 128, 142, 149 Anatomical, 81, 128, 131, 140, 143, 153, 174 Anemia, 128, 148 Anesthesia, 20, 23, 28, 53, 68, 128, 146, 159, 169 Anesthetics, 128, 147 Aneurysm, 128, 149, 182 Anginal, 127, 128, 129, 132, 162 Angioplasty, 27, 28, 31, 42, 128, 160 Angiotensin-Converting Enzyme Inhibitors, 128, 129 Angiotensinogen, 128, 172 Anhydrous, 72, 82, 129 Animal model, 12, 129 Anionic, 77, 87, 129 Anions, 127, 129, 155, 175 Anorectal, 92, 129 Antagonism, 129 Antianginal, 16, 38, 100, 128, 129 Antiarrhythmic, 128, 129, 156, 179 Antibiotic, 129, 147, 161, 176 Antibodies, 129, 130, 150, 167 Antibody, 126, 129, 139, 150, 151, 158, 171, 176 Anticoagulant, 129, 170, 183 Antidote, 129, 135 Antiemetic, 129, 130, 137 Antifungal, 129, 155, 175 Antigen, 126, 129, 130, 139, 141, 142, 151, 152, 153, 158, 171 Antigen-presenting cell, 129, 142 Antihypertensive, 4, 5, 15, 16, 39, 46, 73, 91, 127, 129, 132, 153, 162, 179 Antihypertensive Agents, 4, 39, 73, 91, 129 Anti-inflammatory, 125, 130, 131, 136, 149, 153

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Anti-Inflammatory Agents, 130, 131, 136 Antineoplastic, 130, 162, 175, 182 Antineoplastic Agents, 130, 162, 182 Antioxidant, 130, 131 Antiproliferative, 48, 130 Antipsychotic, 130, 137 Antipyretic, 125, 130 Antiseptic, 125, 130 Antiserum, 130, 141 Antispasmodic, 20, 130, 143, 176 Antitussive, 130, 142 Anus, 128, 129, 130, 134, 139 Anxiety, 126, 130, 169 Anxiolytic, 130, 159 Aorta, 130, 135, 141, 172, 182 Aplastic anemia, 22, 130 Apolipoproteins, 130, 156 Aqueous, 84, 130, 132, 142 Arachidonic Acid, 131, 169 Arginine, 131, 163 Arrestin, 86, 131 Arterial, 5, 48, 92, 131, 137, 152, 156, 162, 163, 170, 178 Arteries, 21, 67, 80, 130, 131, 133, 134, 136, 141, 157, 160, 162, 171 Arteriography, 40, 131 Arteriolar, 32, 131, 134, 148 Arterioles, 80, 131, 133, 135, 160, 162, 182 Artery, 4, 17, 24, 26, 31, 42, 44, 54, 66, 128, 131, 134, 136, 141, 145, 146, 148, 160, 171, 172 Ascorbic Acid, 68, 131 Aspartate, 131, 142 Aspirin, 77, 131 Assay, 14, 32, 44, 131, 171 Asymptomatic, 7, 131 Atenolol, 28, 39, 41, 51, 60, 64, 131 Atrial, 15, 25, 26, 27, 28, 36, 42, 48, 52, 53, 56, 99, 128, 131, 151, 183 Atrial Fibrillation, 15, 25, 26, 27, 28, 36, 42, 48, 53, 56, 131, 183 Atrioventricular, 80, 131, 178 Atrioventricular Node, 131, 178 Atrium, 131, 135, 178, 182 Attenuated, 131, 143 Attenuation, 21, 131 Auscultation, 131, 150 Autacoids, 132, 153 Autonomic Neuropathy, 4, 132 B Bacteria, 129, 132, 145, 146, 148, 159, 174, 176, 180, 181

Bactericidal, 132, 147 Bacteriostatic, 132, 147 Base, 80, 81, 82, 127, 132, 155 Benign, 81, 93, 132, 150 Benign prostatic hyperplasia, 81, 132 Bepridil, 5, 18, 93, 132 Beta blocker, 4, 5, 25, 38, 132 Bethanechol, 48, 53, 93, 132 Bilateral, 132, 173 Bile, 75, 132, 149, 156, 177, 179 Bile Acids, 132, 177, 179 Bile Acids and Salts, 132 Biliary, 132, 143 Bilirubin, 127, 132 Binding Sites, 8, 132 Bioavailability, 10, 18, 20, 25, 37, 50, 55, 74, 75, 79, 133 Biochemical, 56, 133, 174 Bioequivalent, 86, 133 Biological Transport, 133, 143 Biopsy, 133, 165 Biosynthesis, 131, 133, 157, 175 Biotechnology, 12, 13, 95, 101, 109, 133 Bladder, 81, 132, 133, 140, 142, 153, 169, 181 Bloating, 133, 155 Blood Coagulation, 133, 134 Blood Glucose, 39, 133, 154 Blood Platelets, 133, 174 Blood vessel, 132, 133, 134, 136, 137, 145, 146, 149, 155, 158, 166, 175, 177, 179, 182 Blot, 11, 133 Body Fluids, 127, 133, 134, 145, 167, 176 Bolus, 85, 93, 133 Bolus infusion, 133 Bone Marrow, 125, 130, 133, 141, 157 Bone metastases, 134, 138 Bowel, 96, 128, 134, 154, 156, 177 Bowel Movement, 96, 134, 177 Brachial, 134, 171 Brachial Artery, 134, 171 Bradykinin, 134, 163, 167 Bronchi, 134, 147 Bronchial, 132, 134, 151 Bronchial Spasm, 132, 134 Bronchospasm, 60, 134 Buccal, 134, 157 Bulking Agents, 96, 134 Bupivacaine, 134, 156 Bypass, 22, 43, 44, 134, 160 C Cachexia, 11, 134

187

Calcification, 67, 68, 134 Calcinosis, 16, 50, 134 Calcitonin, 68, 134 Calcium blocker, 61, 134 Calcium Channel Blockers, 4, 5, 40, 60, 73, 81, 91, 93, 129, 135, 162 Calcium Channels, 7, 64, 86, 135, 159, 180 Calcium Chloride, 50, 63, 135 Calmodulin, 8, 56, 132, 135 Calpain, 11, 135 Capillary, 134, 135, 149 Capsules, 14, 45, 75, 76, 92, 100, 135, 144, 149 Carbohydrate, 91, 135 Carbon Dioxide, 135, 142, 172 Carcinogen, 126, 135 Cardiac arrest, 60, 64, 135 Cardiomyopathy, 7, 9, 13, 36, 53, 135 Cardiopulmonary, 25, 135 Cardiopulmonary Bypass, 25, 135 Cardiorespiratory, 135, 159 Cardioselective, 131, 135, 136, 169 Cardiotonic, 135, 144 Cardiovascular Abnormalities, 7, 136 Cardiovascular disease, 5, 9, 136 Cardiovascular System, 7, 132, 136, 143 Carotene, 136, 173 Carotid Arteries, 64, 136 Carrier Proteins, 136, 167, 171 Case report, 30, 54, 136, 138 Case series, 136, 138 Catabolism, 11, 136 Catecholamine, 136, 144 Catheterization, 128, 136, 160 Cations, 136, 155 Causal, 6, 136 Celecoxib, 12, 136 Celiprolol, 38, 136 Cell Death, 9, 136, 161 Cell Differentiation, 136, 175 Cell membrane, 80, 133, 135, 136, 137, 142, 149, 166, 183 Cell proliferation, 137, 175 Cell Respiration, 137, 159, 172 Cell Survival, 10, 137 Central Nervous System, 125, 135, 137, 149, 150, 157, 161, 164, 174 Centrifugation, 137, 178 Cerebral, 64, 88, 137, 141, 147, 148, 176 Cerebral Cortex, 137, 147, 148 Cerebrovascular, 4, 135, 136, 137, 162 Cerebrum, 137

Cervical, 25, 137 Cervix, 137 Character, 128, 137, 142 Chest Pain, 4, 137 Chloroquine, 19, 137 Chlorpromazine, 89, 137 Cholesterol, 132, 137, 138, 141, 144, 156, 157, 174, 175, 177, 179 Cholesterol Esters, 137, 156 Cholinergic, 92, 130, 138 Chorioretinitis, 138, 173 Choroid, 138, 173 Chromatin, 138, 157, 176 Chronic, 3, 9, 13, 14, 18, 23, 27, 28, 43, 44, 45, 49, 50, 51, 53, 56, 66, 74, 75, 76, 82, 87, 88, 91, 93, 96, 100, 129, 134, 138, 143, 146, 149, 155, 168, 177, 178, 181, 183 Chronic Disease, 9, 134, 138 Chronic Fatigue Syndrome, 96, 138 Chronic renal, 3, 51, 91, 138, 149, 168 Chronotropic, 34, 138 Chylomicrons, 138, 156 CIS, 73, 74, 79, 82, 89, 138, 152, 173 Clamp, 7, 138 Clinical Medicine, 138, 168 Clinical study, 46, 138 Clinical trial, 6, 12, 36, 49, 50, 97, 109, 138, 140, 141, 144, 171 Clodronate, 44, 138 Cloning, 133, 138, 156 Coagulation, 133, 138, 151, 167, 183 Codeine, 139, 142 Coenzyme, 69, 131, 139, 157, 162, 175 Cofactor, 139, 170 Colestipol, 25, 139 Colitis, 139, 155 Colloidal, 127, 139, 175 Colon, 14, 23, 53, 139, 155, 156 Comorbidity, 9, 139 Complement, 139, 167 Complementary and alternative medicine, 63, 70, 139 Complementary medicine, 63, 139 Compliance, 89, 140 Comprehensive Health Care, 9, 140 Computational Biology, 109, 140 Concomitant, 25, 41, 140 Conduction, 7, 63, 80, 131, 140 Cone cells, 140, 180 Cones, 140, 173 Confounding, 9, 140 Congestion, 130, 140

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Congestive heart failure, 17, 26, 27, 73, 140, 156 Connective Tissue, 131, 133, 140, 142, 148, 149, 157, 178 Consciousness, 127, 128, 140, 144, 170, 173 Constipation, 93, 130, 140, 148, 155 Constitutional, 140, 173 Constriction, 140, 155, 182 Constriction, Pathologic, 140, 182 Contractility, 7, 128, 140, 145 Contraindications, ii, 140 Contrast medium, 140, 141 Control group, 6, 9, 140 Controlled study, 26, 140 Convulsions, 141, 145 Coronary Angiography, 20, 141 Coronary Arteriosclerosis, 141, 160 Coronary Artery Bypass, 24, 25, 28, 36, 65, 141 Coronary Circulation, 128, 141, 163 Coronary heart disease, 136, 141 Coronary Thrombosis, 141, 160 Corpus, 141, 165 Corticosteroids, 141, 149, 168 Cortisol, 127, 141 Creatinine, 12, 141 Cross Reactions, 40, 141 Cryopreservation, 141, 143 Crystallization, 72, 91, 141 Curative, 141, 173, 179 Cutaneous, 16, 19, 30, 57, 141, 157 Cyanide, 141, 159 Cyclic, 86, 91, 135, 141, 150, 163, 166, 169, 174, 180 Cyclosporine, 14, 15, 22, 29, 34, 40, 41, 45, 47, 56, 141, 152 Cyst, 12, 141 Cystitis, 81, 142 Cytokine, 142, 175 Cytoplasm, 137, 142, 150, 157, 161, 178 Cytoskeletal Proteins, 135, 142, 145 Cytotoxic, 142, 153, 175 Cytotoxicity, 67, 142 D Dantrolene, 11, 142 Degenerative, 86, 142, 151, 157 Delusions, 142, 170 Demethylation, 22, 51, 142 Dendrites, 142, 161 Dendritic, 23, 142, 158 Dendritic cell, 23, 142 Dental Hygienists, 5, 142

Depolarization, 65, 142, 175 Dermis, 142, 180 Desensitization, 7, 142, 153 Dextromethorphan, 77, 142 Diagnostic procedure, 71, 101, 142 Dialyzer, 143, 151 Diarrhea, 143, 148, 155 Diastole, 143 Diastolic, 28, 143, 152 Dicyclomine, 96, 143 Dietary Fats, 143, 156 Diffusion, 77, 133, 143 Digestion, 132, 134, 143, 154, 156, 177 Digestive tract, 92, 132, 143 Dihydropyridines, 5, 7, 143 Dilatation, Pathologic, 143, 182 Dilated cardiomyopathy, 17, 36, 143 Dilation, 134, 143, 182 Dilator, 143, 163 Dilution, 92, 143 Dimethyl, 82, 143, 155, 157, 162 Dimethyl Sulfoxide, 83, 143 Direct, iii, 10, 103, 138, 143, 144, 151, 166, 171, 172, 178 Discrete, 143 Discriminant Analysis, 18, 143 Disease Progression, 12, 143 Disinfectant, 144, 147 Disposition, 18, 22, 25, 26, 47, 65, 144 Dissociation, 126, 144, 180 Distal, 93, 141, 144, 170 Distention, 96, 144 Diuretic, 37, 90, 91, 135, 144, 148, 153 Diuretics, Thiazide, 129, 144 Dobutamine, 24, 144 Dopamine, 25, 130, 137, 144, 162, 166 Dosage Forms, 50, 76, 78, 79, 87, 88, 144 Double-blind, 12, 14, 17, 30, 38, 41, 52, 144 Double-blinded, 12, 144 Doxazosin, 39, 144 Drip, 52, 144 Drug Combinations, 6, 144 Drug Delivery Systems, 22, 76, 85, 145 Drug Interactions, 5, 10, 66, 104, 145 Duct, 136, 145, 157, 177 Duodenum, 132, 145, 146, 177 Dystrophin, 145, 160 E Echocardiography, 24, 26, 145 Effector, 125, 139, 145, 166 Efficacy, 4, 12, 14, 16, 20, 21, 28, 32, 34, 39, 42, 45, 51, 55, 91, 145

189

Ejection fraction, 32, 145 Elastic, 145, 176, 178 Electroconvulsive Therapy, 53, 145 Electrolyte, 127, 145, 168, 176 Electrons, 130, 132, 145, 155, 165, 171 Emboli, 145, 183 Embolism, 145, 171, 183 Embolization, 145, 183 Embolus, 145, 153 Embryo, 137, 146, 153, 163 Enalapril, 38, 146 Encephalopathy, 22, 146 Endarterectomy, 128, 146 Endocrine Glands, 146, 165 Endogenous, 7, 135, 144, 146, 170 Endorphins, 146, 162 Endoscopic, 146, 159 Endothelial cell, 67, 146 Endothelium, 146, 163 Endothelium-derived, 146, 163 Endotoxin, 146, 163 End-stage renal, 11, 52, 138, 146, 168 Enkephalins, 146, 162 Environmental Health, 108, 110, 146 Enzymatic, 72, 83, 84, 91, 134, 136, 139, 146, 151, 173 Epidermis, 142, 146, 152, 171 Epidural, 25, 146 Epinephrine, 63, 126, 144, 146, 162, 163, 181 Erectile, 89, 90, 147, 165 Erection, 147 Erythrocytes, 128, 133, 135, 147 Erythromycin, 10, 147 Esophagus, 143, 147, 177, 179 Estrogen, 10, 147, 174, 179 Ethanol, 7, 65, 83, 147 Eukaryotic Cells, 142, 147, 181 Evacuation, 140, 147, 156 Evoke, 147, 177 Excitation, 7, 142, 147, 162, 180 Excrete, 147, 155, 172 Exercise Test, 51, 147 Exercise Tolerance, 28, 147 Exogenous, 146, 147, 170 Exon, 127, 147 Extracellular, 65, 140, 147, 176, 179 Extracorporeal, 40, 147, 148 Extracorporeal Membrane Oxygenation, 40, 148 Extraction, 10, 18, 33, 148 Extrapyramidal, 130, 144, 148

Extremity, 148, 156 F Family Planning, 109, 148 Fat, 126, 131, 132, 133, 136, 141, 145, 148, 155, 156, 178, 180 Fatigue, 138, 148, 150 Fatty acids, 127, 148, 169 Feces, 140, 148, 177 Felodipine, 5, 20, 39, 65, 93, 148 Femoral, 135, 148 Femoral Artery, 135, 148 Fentanyl, 25, 127, 148 Fibrosis, 148, 174 Fissure, 93, 148 Foetoplacental, 148, 163 Folate, 148 Fold, 83, 148, 158, 164 Folic Acid, 90, 148 Forearm, 32, 133, 148, 171 Fractionation, 148, 178 Functional Disorders, 96, 148 Furosemide, 148, 153 G Galenical, 80, 149 Gallbladder, 125, 132, 149 Gallopamil, 30, 42, 60, 149 Ganglia, 125, 130, 149, 161, 166 Ganglionic Blockers, 129, 149 Gap Junctions, 149 Gas, 135, 143, 148, 149, 152, 155, 163, 173, 178 Gastric, 144, 149, 151 Gastrointestinal, 48, 75, 76, 78, 134, 143, 147, 149, 174, 177, 181 Gastrointestinal tract, 75, 78, 147, 149, 174 Gene, 11, 95, 127, 133, 145, 149, 156, 167, 170 Genital, 132, 149 Genomics, 8, 149 Genotype, 26, 47, 127, 149 Germ Cells, 149, 158, 164, 176, 179 Gland, 126, 149, 157, 165, 169, 170, 174, 177, 179 Glomerular, 5, 149, 154, 162, 172 Glomerular Filtration Rate, 5, 149, 162 Glomerulus, 149, 161 Glucocorticoid, 11, 149, 168 Glucose, 85, 131, 133, 150, 154, 166 Glutamate, 142, 150 Glutamic Acid, 148, 150, 162 Glycine, 132, 150, 162 Glycoprotein, 18, 150

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Diltiazem

Governing Board, 150, 168 Graft, 28, 40, 127, 150, 153, 160 Graft Rejection, 40, 150, 153 Grafting, 24, 25, 36, 65, 141, 150, 153 Granulocytes, 150, 175, 183 Grasses, 148, 150 Guanylate Cyclase, 150, 162, 163 H Half-Life, 74, 76, 87, 150 Haptens, 126, 150, 171 Headache, 150, 168 Heart attack, 136, 150 Heart failure, 7, 13, 128, 150 Heart Murmurs, 5, 150, 151 Heart Sounds, 150 Hemodialysis, 52, 143, 151, 155 Hemodynamics, 53, 151 Hemorrhage, 19, 150, 151, 160, 171, 177 Hemostasis, 151, 174 Hepatic, 10, 29, 51, 79, 127, 151, 175 Hepatitis, 52, 151, 166 Hepatocytes, 151 Heredity, 149, 151 Heterogeneity, 126, 151 Histamine, 130, 151, 157 Homeostasis, 9, 151 Homologous, 151, 178 Hormone, 127, 134, 141, 146, 151, 154, 163, 174, 175, 179 Hospital Charges, 151 Hospital Costs, 25, 151 Humoral, 150, 151 Hydration, 77, 151 Hydrogel, 66, 152 Hydrogen, 125, 132, 135, 143, 152, 159, 164 Hydrolysis, 72, 83, 152, 166, 180 Hydrophilic, 75, 152 Hydrophobic, 152, 156 Hypercalcemia, 138, 152 Hyperpigmentation, 24, 152 Hyperplasia, 5, 30, 152 Hyperreflexia, 152, 179 Hypersensitivity, 127, 142, 152 Hyperthyroidism, 152, 169 Hypertrophy, 132, 152 Hypnotic, 152, 159 Hypotension, 4, 25, 130, 132, 141, 149, 152 Hypotensive, 61, 152 Hypoxic, 32, 152 I Idiopathic, 81, 152 Ileus, 46, 152

Imidazole, 67, 73, 151, 152 Immune response, 126, 129, 150, 152, 153, 177, 182 Immunogenic, 152, 171 Immunology, 23, 126, 152 Immunophilins, 152, 175 Immunosuppressant, 152, 153, 175 Immunosuppression, 37, 153, 157 Immunosuppressive, 149, 153, 179 Immunosuppressive Agents, 153 Immunotherapy, 142, 153 Impairment, 153, 158, 170 Implantation, 153, 163 Impotence, 147, 153 In vitro, 10, 22, 29, 44, 153, 179 In vivo, 10, 11, 65, 87, 153, 157, 179 Incision, 153, 154 Incontinence, 143, 153 Incubated, 11, 153 Indapamide, 15, 153 Indomethacin, 29, 77, 153 Induction, 130, 149, 153, 175 Infancy, 153, 173 Infarction, 34, 39, 153, 172 Infections, 125, 129, 150, 153 Infusion, 21, 23, 85, 154, 160 Ingestion, 5, 7, 76, 87, 154, 168, 179 Inhalation, 154, 168 Innervation, 81, 154 Inoperable, 41, 154 Inorganic, 154, 155, 160, 162 Inositol, 154, 174 Inotropic, 43, 131, 144, 148, 154 Insomnia, 154, 168 Insulin, 37, 154, 155 Insulin-dependent diabetes mellitus, 154 Intensive Care, 19, 154 Intermittent, 88, 154 Interstitial, 49, 81, 154, 161, 172 Intestinal, 10, 136, 154 Intestinal Mucosa, 10, 154 Intestine, 29, 76, 132, 134, 145, 151, 154, 156 Intoxication, 7, 154, 183 Intracellular, 8, 10, 80, 135, 154, 163, 168, 169, 171, 174, 175 Intramuscular, 90, 154 Intravenous, 16, 17, 21, 25, 29, 32, 36, 39, 42, 43, 48, 54, 60, 64, 74, 75, 90, 154 Intrinsic, 126, 154 Inulin, 149, 154 Invasive, 44, 154

191

Involuntary, 155, 160, 161, 172, 176 Ions, 74, 75, 76, 85, 87, 88, 132, 135, 144, 145, 152, 155, 158 Iron Compounds, 85, 155 Irritable Bowel Syndrome, 96, 148, 155 Ischemia, 16, 37, 43, 64, 100, 155, 160, 172 Isosorbide Dinitrate, 13, 155 Isradipine, 5, 43, 93, 155 K Kb, 108, 155 Ketanserin, 39, 155 Ketoacidosis, 125, 155 Ketoconazole, 14, 53, 155 Ketone Bodies, 125, 155 Kidney Disease, 11, 15, 108, 155 Kidney Failure, 146, 155 Kinetic, 72, 82, 155 L Lactation, 155, 164 Lag, 74, 85, 87, 156 Large Intestine, 143, 154, 156, 172 Laxative, 126, 156, 158 Leg Ulcer, 55, 156 Lesion, 9, 141, 156, 181 Lethal, 11, 38, 132, 141, 156 Leukemia, 67, 156 Levo, 156, 179 Levorphanol, 142, 156 Lidocaine, 20, 156 Lidoflazine, 93, 156 Ligaments, 141, 156 Ligase, 11, 156 Ligation, 11, 156 Lipase, 72, 156 Lipid, 91, 130, 154, 156, 159, 180 Lipoprotein, 55, 156, 157 Lisinopril, 38, 39, 156 Liver, 10, 22, 34, 40, 47, 74, 75, 79, 125, 127, 131, 132, 135, 137, 142, 148, 149, 151, 156, 157, 163, 171 Localized, 145, 156, 167, 181 Loop, 5, 48, 156 Loperamide, 48, 157 Lovastatin, 157, 175 Low-density lipoprotein, 156, 157 Lubricants, 77, 157 Lupus, 19, 157, 178 Lymph, 137, 146, 157 Lymph node, 137, 157 Lymphoblasts, 125, 157 Lymphocyte Depletion, 153, 157

Lymphocytes, 6, 129, 142, 157, 176, 179, 183 Lymphocytic, 157 Lymphoid, 129, 141, 157 Lysine, 72, 157 M Macula, 157 Macula Lutea, 157 Macular Degeneration, 86, 157 Malnutrition, 127, 134, 157 Mammary, 21, 24, 141, 157, 179 Mammogram, 134, 157, 159 Manic, 130, 157, 158, 170 Manic-depressive psychosis, 158, 170 Mediate, 144, 158 Mediator, 158, 174 Medical Staff, 144, 158 MEDLINE, 109, 158 Medullary, 142, 158 Megaloblastic, 148, 158 Meiosis, 158, 178 Melanin, 158, 166, 181 Melanocytes, 152, 158 Membrane Potentials, 8, 158 Menopause, 158, 164, 168, 169 Menstrual Cycle, 158, 163, 168 Mental, iv, 6, 108, 110, 137, 144, 148, 158, 170, 174, 181 Mental Disorders, 158, 170 Mesenteric, 48, 158, 168 Mesentery, 158, 177 Metabolite, 10, 44, 55, 143, 157, 158, 169, 171 Methylcellulose, 60, 76, 158 Methylene Blue, 25, 159 Methylprednisolone, 46, 159 Metoprolol, 21, 51, 55, 159 Mibefradil, 38, 159 Microbe, 159, 180 Microcalcifications, 134, 159 Microorganism, 139, 159, 183 Microscopy, 11, 159 Microspheres, 19, 52, 159 Midazolam, 10, 65, 159 Migration, 37, 66, 159 Miscible, 83, 159, 166 Mitochondria, 9, 159, 160 Mitochondrial Swelling, 159, 161 Modification, 16, 41, 77, 159, 171 Molecular, 8, 10, 42, 67, 76, 109, 111, 133, 135, 140, 159, 172

192

Diltiazem

Molecule, 125, 129, 132, 133, 139, 144, 145, 146, 147, 152, 155, 159, 165, 166, 171, 175, 182 Monitor, 25, 141, 159, 163 Monophosphate, 86, 160 Monotherapy, 42, 45, 64, 91, 160 Motility, 65, 148, 153, 160, 174 Motion Sickness, 160, 161 Mucosa, 10, 157, 160 Mucus, 25, 160 Muscle Fibers, 131, 160, 161, 181 Muscle Proteins, 11, 160 Muscle relaxant, 142, 160, 177 Muscle Relaxation, 160, 177 Myocardial infarction, 5, 17, 26, 29, 31, 36, 39, 40, 141, 144, 160, 169, 183 Myocardial Ischemia, 26, 74, 75, 76, 87, 88, 128, 160 Myocardial Reperfusion, 17, 160, 172 Myocardial Reperfusion Injury, 160, 172 Myocardium, 43, 128, 160 Myoclonus, 24, 161 Myofibrils, 11, 135, 145, 161 Myosin, 11, 161, 181 N Narcotic, 148, 156, 161 Nausea, 96, 129, 130, 144, 161, 168, 181 NCI, 1, 107, 138, 161 Necrosis, 55, 153, 160, 161, 172, 173 Nephritis, 49, 161 Nephropathy, 5, 155, 161 Nerve Endings, 161, 178 Nerve Growth Factor, 81, 161 Nervous System, 7, 128, 137, 158, 161, 162, 166, 178 Netilmicin, 12, 161 Neuromuscular, 125, 142, 161 Neuromuscular Junction, 125, 161 Neuronal, 135, 161, 162 Neurons, 142, 149, 160, 161, 162, 178 Neuropathy, 132, 162, 166 Neuropeptides, 135, 162 Neurophysiology, 142, 162 Neuroretinitis, 162, 173 Neurotoxicity, 142, 162 Neurotransmitter, 8, 125, 126, 134, 144, 150, 151, 162, 163, 174, 175, 177 Niacinamide, 162 Nicardipine, 5, 20, 27, 32, 35, 93, 162 Nicorandil, 60, 162 Nifedipine, 4, 5, 6, 7, 13, 18, 30, 34, 35, 37, 43, 45, 46, 52, 56, 60, 64, 65, 93, 162

Night Blindness, 162, 173 Nimodipine, 5, 93, 162 Nisoldipine, 5, 93, 162 Nitrates, 17, 162 Nitrendipine, 93, 162 Nitric acid, 162, 163 Nitric Oxide, 93, 163 Nitric-Oxide Synthase, 43, 163 Nitrogen, 127, 163, 181 Nitroglycerin, 22, 24, 39, 43, 44, 155, 163 Norepinephrine, 67, 126, 144, 162, 163 Normotensive, 38, 163 Nuclear, 145, 147, 161, 163 Nucleus, 138, 141, 142, 147, 157, 158, 163, 169 O Observational study, 9, 163 Oestradiol, 53, 163 Oestrogen, 53, 163 Ointments, 144, 164 Omentum, 164, 177 Opsin, 164, 173 Optic Nerve, 162, 164, 173 Oral Health, 164 Oral Hygiene, 5, 164 Orthostatic, 4, 130, 164 Osmosis, 164 Osmotic, 85, 90, 127, 159, 164, 175 Ossification, 164, 173 Osteoclasts, 134, 164 Osteoporosis, 164 Ovary, 163, 164 Overdosage, 40, 54, 164 Overdose, 14, 28, 31, 37, 40, 41, 44, 46, 51, 52, 60, 64, 164 Overexpress, 9, 164 Oxidation, 63, 125, 130, 164 Oxygen Consumption, 147, 165, 172 Oxygenator, 135, 148, 165 P Palliative, 164, 165, 179 Pancreas, 125, 154, 156, 165, 177 Panniculitis, 19, 165 Parathyroid, 65, 165, 173, 179 Parathyroid Glands, 165, 173 Parathyroid hormone, 65, 165 Paroxysmal, 16, 26, 36, 128, 165 Particle, 165, 176, 180 Patch, 7, 15, 165, 180 Pathologic, 133, 134, 141, 152, 165 Pathologies, 86, 165 Patient Compliance, 76, 78, 79, 87, 88, 165

193

Pelvic, 81, 165, 169 Pelvis, 125, 165, 181 Penis, 90, 165 Peptide, 8, 134, 165, 170 Percutaneous, 27, 28, 31, 165 Perfusion, 37, 165 Perhexiline, 93, 166 Periodicity, 166, 173 Perioperative, 52, 166 Peripheral Nervous System, 146, 162, 166, 177 Peripheral vision, 166, 183 Personal Health Services, 140, 166 Pharmaceutical Preparations, 77, 147, 166 Pharmaceutical Solutions, 144, 166 Pharmacodynamic, 46, 166 Pharmacokinetic, 10, 30, 32, 40, 42, 46, 47, 60, 166 Pharmacologic, 48, 128, 132, 150, 166, 180, 181 Phenyl, 132, 166 Phenylalanine, 166, 181 Phosphodiesterase, 86, 166, 180 Phospholipases, 166, 175 Phospholipids, 148, 154, 156, 166 Phosphorus, 134, 165, 166 Phosphorylase, 135, 166 Phosphorylated, 131, 139, 167 Photoreceptor, 86, 167, 173 Physiologic, 126, 133, 150, 154, 158, 161, 167, 169, 171, 180 Physiology, 7, 125, 162, 167 Pigmentation, 152, 167 Pigments, 136, 167, 173 Pilot study, 12, 167 Plants, 127, 135, 150, 154, 163, 167, 174, 180 Plaque, 5, 128, 167 Plasma cells, 6, 129, 167 Plasma protein, 127, 167, 175 Plasticity, 8, 167 Plasticizers, 77, 167 Platelet Activation, 27, 167, 175 Platelet Aggregation, 155, 163, 167 Platelets, 135, 163, 167 Pneumoconiosis, 52, 167 Pneumonia, 140, 168 Poisoning, 38, 135, 154, 159, 161, 168 Polycystic, 11, 168 Polymers, 76, 168, 170 Portal Vein, 79, 168 Posterior, 128, 138, 165, 168

Postmenopausal, 53, 164, 168 Postsynaptic, 168, 175 Post-synaptic, 168, 178 Potassium, 68, 83, 127, 144, 158, 162, 168 Potassium hydroxide, 83, 168 Potentiation, 42, 48, 67, 168, 175 Practice Guidelines, 110, 168 Precursor, 84, 85, 128, 131, 144, 145, 146, 163, 166, 168, 169, 181 Prednisolone, 159, 168 Premenstrual Syndrome, 96, 168 Preoperative, 28, 168 Presynaptic, 161, 162, 168, 178 Procaine, 156, 168 Prodrug, 169, 171 Progression, 4, 5, 12, 81, 129, 169 Progressive, 11, 54, 136, 138, 161, 167, 169, 172, 173 Progressive disease, 11, 169 Projection, 163, 164, 169 Prophase, 169, 178 Prophylaxis, 27, 142, 169, 183 Propranolol, 17, 32, 54, 55, 60, 64, 77, 131, 169, 179 Prospective study, 23, 169 Prostaglandin, 60, 89, 128, 169 Prostaglandins A, 153, 169 Prostate, 132, 164, 169, 170 Prostatic Hyperplasia, 170 Protective Agents, 135, 170 Protein Binding, 41, 170 Protein C, 127, 130, 156, 160, 170, 181 Protein Isoforms, 127, 170 Protein S, 95, 133, 147, 170 Proteinuria, 4, 5, 170 Proximal, 144, 168, 170 Psychoactive, 170, 183 Psychosis, 46, 130, 170 Psyllium, 96, 170 Public Policy, 109, 170 Publishing, 3, 12, 170 Pulmonary, 32, 39, 44, 45, 66, 114, 133, 147, 150, 155, 170, 171, 175, 178, 179, 182, 183 Pulmonary Artery, 133, 170, 171, 182 Pulmonary congestion, 39, 170 Pulmonary Edema, 44, 155, 170 Pulmonary Embolism, 171, 183 Pulmonary hypertension, 32, 45, 66, 171 Pulse, 78, 160, 171 Purpura, 13, 45, 171

194

Diltiazem

Q Quality of Life, 90, 171 Quaternary, 87, 91, 171, 177 R Race, 72, 83, 84, 159, 171 Racemic, 72, 83, 84, 171 Radial Artery, 21, 36, 171 Radiation, 128, 148, 153, 171, 183 Radioactive, 150, 152, 153, 163, 171 Radioimmunoassay, 44, 171 Radiological, 165, 171 Ramipril, 16, 171 Randomized, 12, 14, 17, 26, 28, 30, 38, 41, 42, 49, 50, 51, 52, 145, 171 Reaction Time, 83, 171 Reagent, 84, 171 Reality Testing, 170, 171 Receptor, 11, 73, 125, 129, 142, 144, 155, 167, 171, 174, 175 Receptors, Serotonin, 171, 174 Rectum, 14, 23, 53, 129, 130, 134, 139, 143, 149, 153, 156, 170, 172 Recurrence, 26, 158, 166, 172 Reductase, 157, 172, 175 Refer, 1, 134, 139, 146, 157, 170, 172 Reflex, 16, 172 Refractory, 52, 68, 172 Regeneration, 83, 172 Regimen, 76, 87, 145, 165, 172 Regression Analysis, 143, 172 Relaxant, 172, 177 Remission, 158, 172 Renal Artery, 4, 172 Renal failure, 4, 172 Renal tubular, 24, 172 Renin, 11, 91, 128, 172 Reperfusion, 60, 64, 67, 68, 160, 172 Reperfusion Injury, 68, 172 Respiration, 135, 159, 172, 173 Respiratory failure, 148, 173 Resuscitation, 60, 64, 173 Retina, 138, 140, 157, 162, 164, 173, 181 Retinal, 86, 131, 164, 173 Retinitis, 54, 86, 173 Retinitis Pigmentosa, 54, 86, 173 Retinol, 173 Rhabdomyolysis, 51, 52, 173 Rheumatoid, 137, 173 Rhodopsin, 86, 131, 164, 173, 180 Rhythmicity, 7, 173 Rickets, 67, 68, 173 Risk factor, 169, 173

Rod, 86, 138, 167, 173, 180 Rod cells, 173, 180 S Saphenous, 141, 173, 174 Saphenous Vein, 141, 174 Saponin, 67, 174 Sarcomere, 11, 174 Schizoid, 174, 183 Schizophrenia, 145, 174, 183 Schizotypal Personality Disorder, 174, 183 Sclerosis, 37, 174 Screening, 138, 174 Second Messenger Systems, 7, 174 Secretion, 65, 143, 151, 154, 155, 160, 174 Secretory, 174 Secular trends, 9, 174 Sedative, 139, 159, 174 Seizures, 165, 174 Selective estrogen receptor modulator, 174, 179 Seminiferous tubule, 174, 176 Sepsis, 11, 174 Septic, 11, 174 Serotonin, 21, 130, 155, 162, 171, 174, 181 Serum, 12, 18, 33, 39, 44, 78, 79, 88, 127, 130, 139, 144, 157, 171, 174, 175 Serum Albumin, 171, 175 Sex Characteristics, 163, 175 Shock, 60, 161, 175, 180 Side effect, 5, 30, 53, 74, 75, 76, 87, 88, 96, 103, 126, 130, 175, 180 Signal Transduction, 7, 9, 154, 175 Simvastatin, 34, 51, 52, 61, 175 Sirolimus, 47, 152, 175 Skeletal, 11, 66, 138, 142, 161, 173, 175, 176, 177, 181 Skeleton, 125, 169, 175 Smoke Inhalation Injury, 148, 175 Smoking Cessation, 5, 175 Smooth muscle, 37, 66, 80, 96, 132, 134, 135, 148, 151, 155, 163, 175, 176, 177 Social Environment, 171, 175 Sodium, 19, 73, 82, 83, 87, 127, 144, 158, 162, 176, 180 Solvent, 72, 80, 81, 82, 83, 84, 85, 125, 143, 147, 164, 166, 176 Sound wave, 140, 176 Spasm, 22, 43, 93, 130, 176, 179 Spasmolytic, 176, 181 Spastic, 155, 176 Spasticity, 142, 176 Specialist, 115, 143, 176

195

Species, 127, 146, 158, 159, 171, 176, 180, 181, 182, 183 Specificity, 126, 135, 176 Spectrum, 155, 176 Sperm, 25, 174, 176, 179, 182 Sperm Motility, 25, 176 Spermatozoa, 65, 176 Spermatozoon, 176 Sphincter, 53, 93, 176 Spinal cord, 134, 137, 146, 161, 162, 166, 172, 176 Spleen, 176, 177 Splenic Artery, 65, 176 Splenic Vein, 168, 177 Statistically significant, 96, 177 Steady state, 79, 177 Steel, 138, 177 Stenosis, 4, 51, 177 Sterile, 165, 177 Steroid, 132, 141, 163, 175, 177 Stimulant, 144, 151, 177 Stimulus, 8, 140, 147, 154, 156, 171, 172, 177, 179 Stomach, 75, 92, 125, 143, 147, 149, 151, 161, 164, 176, 177 Stool, 93, 96, 139, 153, 155, 156, 177 Stress, 9, 24, 64, 136, 141, 148, 155, 161, 177 Stricture, 177 Stridor, 177, 179 Stroke, 5, 7, 108, 136, 177 Subacute, 19, 177 Subarachnoid, 19, 150, 177 Subcutaneous, 90, 165, 177 Substance P, 147, 158, 174, 177 Substrate, 10, 72, 85, 177 Succinylcholine, 68, 177 Suction, 16, 178 Supplementation, 127, 178 Suppression, 67, 178 Supraventricular, 16, 21, 39, 55, 178 Surfactant, 82, 88, 92, 178 Sympathomimetic, 144, 146, 163, 178 Symptomatic, 45, 178 Synapse, 126, 161, 168, 178, 180 Synapsis, 178 Synaptic, 8, 162, 175, 178 Synaptic Vesicles, 178 Synaptosomes, 65, 178 Systemic, 10, 20, 22, 37, 79, 104, 130, 133, 137, 146, 151, 168, 178, 182, 183 Systemic lupus erythematosus, 137, 178 Systemic therapy, 137, 178

Systolic, 4, 20, 152, 178 T Tachycardia, 21, 144, 178 Tacrolimus, 47, 152, 178 Talc, 73, 179 Tamoxifen, 48, 174, 179 Taurine, 54, 132, 179 Teratogenic, 179 Testicles, 179, 182 Testis, 163, 179 Tetany, 50, 165, 179 Therapeutics, 15, 19, 27, 34, 42, 43, 46, 47, 50, 51, 54, 66, 67, 104, 179 Thoracic, 22, 24, 27, 36, 43, 44, 68, 157, 179 Thoracic Surgery, 22, 24, 27, 36, 43, 68, 179 Threshold, 152, 179 Thrombosis, 170, 177, 179 Thyroid, 134, 152, 165, 179, 181 Thyroid Gland, 152, 165, 179 Thyroxine, 127, 166, 179 Timolol, 35, 179 Tone, 132, 163, 164, 176, 179 Topical, 14, 53, 92, 143, 147, 180 Torsion, 153, 180 Toxic, iv, 141, 142, 150, 162, 163, 168, 175, 180 Toxicity, 19, 29, 54, 145, 161, 180 Toxicology, 14, 19, 38, 51, 60, 110, 180 Toxins, 8, 129, 135, 180 Traction, 138, 180 Transdermal, 22, 29, 180 Transducin, 86, 180 Transduction, 9, 175, 180 Transfection, 133, 180 Translation, 147, 180 Translocation, 147, 180 Transmitter, 125, 144, 158, 163, 178, 180 Transplantation, 14, 23, 29, 34, 37, 40, 41, 45, 55, 56, 138, 157, 180 Trauma, 150, 161, 180 Tremor, 179, 180 Triglyceride, 139, 180 Trimebutine, 96, 181 Trimetazidine, 54, 99, 181 Trivalent, 85, 181 Tropomyosin, 160, 181 Troponin, 160, 181 Tryptophan, 174, 181 Tuberculosis, 157, 181 Tunica, 146, 160, 181 Tyrosine, 11, 144, 181

196

Diltiazem

U Ubiquitin, 11, 181 Ulcer, 93, 181 Uremia, 155, 172, 181 Ureters, 172, 181 Urethra, 132, 165, 169, 181 Urinary, 81, 132, 142, 143, 153, 181 Urinary Retention, 132, 181 Urinary tract, 81, 143, 181 Urine, 4, 81, 132, 133, 141, 144, 153, 155, 170, 181 Urodynamic, 81, 181 Uterus, 137, 141, 181 Uveitis, 131, 181 V Vaccine, 126, 181 Varicose, 156, 181 Varicose Ulcer, 156, 181 Vascular Resistance, 128, 148, 182 Vasculitis, 57, 182 Vasectomy, 25, 182 Vasoconstriction, 64, 144, 147, 182 Vasodilatation, 162, 182 Vasodilation, 36, 56, 128, 132, 162, 182 Vasodilator, 44, 129, 134, 144, 149, 151, 155, 156, 160, 162, 166, 181, 182 Vector, 180, 182 Vein, 128, 154, 163, 168, 173, 174, 177, 182 Venous, 156, 162, 163, 170, 181, 182, 183

Venous Thrombosis, 182, 183 Ventricle, 131, 170, 171, 178, 182 Ventricular, 7, 15, 21, 28, 29, 32, 37, 38, 42, 44, 56, 63, 128, 145, 151, 160, 182 Ventricular Dysfunction, 145, 182 Ventricular Function, 28, 32, 182 Verapamil, 4, 5, 15, 19, 21, 32, 34, 39, 42, 43, 56, 60, 68, 81, 89, 93, 149, 182 Veterinary Medicine, 109, 182 Vinca Alkaloids, 182 Vincristine, 68, 182 Viral, 180, 182 Virulence, 131, 180, 182 Virus, 167, 180, 182 Visceral, 132, 182 Visual field, 54, 173, 182 Vitro, 46, 66, 87, 183 Vivo, 10, 46, 79, 87, 157, 183 Voltage-gated, 8, 183 W Warfarin, 30, 183 White blood cell, 125, 129, 153, 157, 160, 167, 183 Withdrawal, 7, 183 X Xenograft, 129, 183 X-ray, 131, 140, 157, 163, 183 Z Ziconotide, 8, 183

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