VERAPAMIL 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., 1960Verapamil: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84679-0 1. Verapamil-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on verapamil. 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 VERAPAMIL ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Verapamil...................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 16 The National Library of Medicine: PubMed ................................................................................ 18 CHAPTER 2. NUTRITION AND VERAPAMIL ..................................................................................... 65 Overview...................................................................................................................................... 65 Finding Nutrition Studies on Verapamil .................................................................................... 65 Federal Resources on Nutrition ................................................................................................... 67 Additional Web Resources ........................................................................................................... 68 CHAPTER 3. ALTERNATIVE MEDICINE AND VERAPAMIL............................................................... 71 Overview...................................................................................................................................... 71 National Center for Complementary and Alternative Medicine.................................................. 71 Additional Web Resources ........................................................................................................... 77 General References ....................................................................................................................... 80 CHAPTER 4. DISSERTATIONS ON VERAPAMIL................................................................................. 81 Overview...................................................................................................................................... 81 Dissertations on Verapamil ......................................................................................................... 81 Keeping Current .......................................................................................................................... 81 CHAPTER 5. PATENTS ON VERAPAMIL ........................................................................................... 83 Overview...................................................................................................................................... 83 Patents on Verapamil................................................................................................................... 83 Patent Applications on Verapamil............................................................................................. 108 Keeping Current ........................................................................................................................ 116 CHAPTER 6. BOOKS ON VERAPAMIL ............................................................................................. 117 Overview.................................................................................................................................... 117 Book Summaries: Online Booksellers......................................................................................... 117 The National Library of Medicine Book Index ........................................................................... 118 Chapters on Verapamil .............................................................................................................. 118 CHAPTER 7. PERIODICALS AND NEWS ON VERAPAMIL ............................................................... 121 Overview.................................................................................................................................... 121 News Services and Press Releases.............................................................................................. 121 Academic Periodicals covering Verapamil ................................................................................. 123 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 125 Overview.................................................................................................................................... 125 U.S. Pharmacopeia..................................................................................................................... 125 Commercial Databases ............................................................................................................... 126 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 131 Overview.................................................................................................................................... 131 NIH Guidelines.......................................................................................................................... 131 NIH Databases........................................................................................................................... 133 Other Commercial Databases..................................................................................................... 135 APPENDIX B. PATIENT RESOURCES ............................................................................................... 137 Overview.................................................................................................................................... 137 Patient Guideline Sources.......................................................................................................... 137 Finding Associations.................................................................................................................. 139 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 141 Overview.................................................................................................................................... 141 Preparation................................................................................................................................. 141
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Finding a Local Medical Library................................................................................................ 141 Medical Libraries in the U.S. and Canada ................................................................................. 141 ONLINE GLOSSARIES................................................................................................................ 147 Online Dictionary Directories ................................................................................................... 147 VERAPAMIL DICTIONARY ...................................................................................................... 149 INDEX .............................................................................................................................................. 229
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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 verapamil 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 verapamil, 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 verapamil, 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 verapamil. 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 verapamil, 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 verapamil. 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 VERAPAMIL Overview In this chapter, we will show you how to locate peer-reviewed references and studies on verapamil.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and verapamil, 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 “verapamil” (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: •
Experience with Intraplaque Injection of Verapamil for Peyronie's Disease Source: Journal of Urology. 168(8): 621-626. August 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study that examined the use of intraplaque injection of verapamil for the treatment of Peyronie's disease, including the drug's effects on pain, curvature, indentation, sexual function, and erectile capacity. A total of 156 men underwent treatment with intraplaque verapamil injection. Of the 140 patients who completed treatment, 73 (60 percent) had an objectively measured decrease in curvature, while 79 men (62 percent) reported a subjective decrease in curvature during the follow up interview. After treatment, 111 men (83 percent) reported an increase in girth, 107
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men (80 percent) an increase in rigidity distal to the plaque, and 92 men (71 percent) an improvement in sexual function. There was no significant difference in response based on duration of disease. Mean follow up was 30.4 months and there was no reported recurrence of penile deformity in those men with an initial posttreatment positive response. The authors conclude that verapamil injection of Peyronie's plaques appears to be a clinically effective treatment option for pain and curvature and can contribute to subjective improvement in sexual function and erectile capacity. The low incidence of complications indicates that this therapy is also clinically safe. Appended to the article is an editorial commentary. 1 table. 30 references.
Federally Funded Research on Verapamil The U.S. Government supports a variety of research studies relating to verapamil. 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 verapamil. 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 verapamil. The following is typical of the type of information found when searching the CRISP database for verapamil: •
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
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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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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 •
Project Title: ANTI-SELECTIN BLOCKER FOR ORGAN ISCHEMIC INJURY Principal Investigator & Institution: Toledo-Pereyra, Luis H.; Director; Biomedica Management Corporation 135 W 41St St, #608 New York, Ny 10036 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-MAR-2003 Description (provided by applicant): Drugs currently available for the treatment of ischemic (lack of blood supply) conditions are not satisfactory. Since selectins have a primordial role in the development of ischemia, we have proposed the use of a recently discovered anti-selectin blocker (TBC-1269) in a feasibility study to determine its protective capabilities under conditions of severe liver, kidney or lower extremity ischemia in the mice. Our specific aims -centered around commercialization of this drug- is: 1. To demonstrate its definitive therapeutic value, 2. To assess the ideal conditions of tissue and organ protection, 3. To determine if the addition of other well known drugs (eg. Verapamil-calcium channel blocker- and Nitroprusside -nitric oxide donor-) will enhance the effect of this novel anti-selectin blocker. Functional, biochemical and molecular studies -determining the response of neutrophils and CXC and C-C chemokines to the ischemic response and treatment will be utilized to characterize this drug for its use in ischemic conditions. Results of this innovative study could significantly improve the clinical means of enhancing the quality of life of million of patients suffering from the large number of maladies associated with ischemia/reperfusion injury. PROPOSED COMMERCIAL APPLICATION: There are no potent anti-ischemic drugs in the market that effectively protect the organ and life of patients suffering from ischemic diseases such as stroke, coronary artery occlusion, shock trauma, transplant related problems and others. Thus, the use of a newly discovered anti-selectin blocker in the treatment of ischemic syndromes will have a definitive effect in the commercial value of this product. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AORTIC DILATION & MARFAN SYNDROME Principal Investigator & Institution: Silverman, David; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 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: ATRIAL FIBRILLATION FOLLOW UP OF RHYTHM MANAGEMENT (AFFIRM) Principal Investigator & Institution: Pritchett, Edward L.; Duke University Durham, Nc 27706 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: CARDIAC CHANNELS--TARGETS OF DRUGS THAT AFFECT KINETICS Principal Investigator & Institution: Hanck, Dorothy A.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: (Verbatim from Investigator's Abstract): Experiments proposed are aimed at determining structural similarities of drug binding sites between channel types for mibefradil (the only highly specific agent for T-type Ca channels known at the present time) and phenylalkylamines, the drug class that competes with mibefradil, and for which some structural information is available for L-type calcium channels. Three channels will be used, the T-type Ca channel alpha lH, as a high affinity target for mibefradil and a somewhat lower affinity target of verapamil, the voltage-gated Na channel, a very low affinity target for mibefradil but a moderate affinity target for verapamil, and HERG, a high affinity target for both mibefradil and verapamil. In each area, experiments proposed combine site-directed mutagenesis, electrophysiology, and molecular modeling. In addition, experiments are proposed that will establish the channel specific or common effects on kinetics that control the action and efficacy of these agents as therapeutic drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHLOROQUINE RESISTANCE AND PFCRT VARIANTS IN PNG Principal Investigator & Institution: Zimmerman, Peter A.; Assistant Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by the applicant): The hypothesis to be tested here is that molecular polymorphisms in the pfcrt (Plasmodium falciparum {PJ] chloroquine resistance transporter) and pfmdrl (Pf multi-drug resistance) genes associated with chloroquine resistant (CQR) Pf alter the physiology of the parasite's digestive vacuole (DV) where chloroquine' s (CQ) anti-parasite activity is believed to occur. Malaria is the leading cause of morbidity and mortality in PNG, and as drug treatment is the only effective means of control for clinical malaria, an improved understanding of mechanisms by which drug resistance evolves, will have an immediate impact on PNG
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health care policy. Our preliminary studies showed that PNG Pf isolates carry pfcrt alleles associated with either CQ sensitivity (CQS, CVMNK) or resistance (CQR, SVMNT) observed previously in Brazilian Pf strains and not the CQR associated CVIET allele observed in more proximal Southeast Asian strains. Further, the CQR phenotype observed in PNG and South American PfSVMNT strains was marked by significantly reduced sensitivity to in in vitro verapamil (VPL) reversal than was observed for CVIET strains. We hypothesize that these pfcrt sequence differences are responsible for CQR characterized by reduced VPL reversibility. As VPL reversibility is considered to be an integral component of PfCQR, clarifying the molecular basis of this phenotype may reveal new insight regarding parasite physiology and promote new development strategies for future anti-malarial drugs. The specific aims are to: 1) Conduct antimalarial treatment therapeutic efficacy trials and from parasites isolated from study volunteers, 2) Correlate in vitro CQ susceptibility phenotypes for PNG Pf with pftrt and pfmdr1 sequence polymorphisms, and 3) Apply newly developed allele replacement strategies to determine how pfcrt and pfmdr1 sequence polymorphisms influence CQ IC50, CQR/VPL reversal and regulation of parasite DV physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIAPHRAGM FATIGUE:MECHANISMS OF TREATMENT BY DOPAMINE Principal Investigator & Institution: Pierce, Janet D.; None; University of Kansas Medical Center Msn 1039 Kansas City, Ks 66160 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 28-FEB-2005 Summary: Thousands of patients suffer from diaphragm fatigue (DF) when being weaned from mechanical ventilation. Failure to wean from ventilation is a costly and time consuming clinical problem, and an emotionally difficult experience for patients. Low dose dopamine frequently is administered to mechanically ventilated patients with the objective of increasing renal blood flow, without any regard to its effect on diaphragmatic function. Our previous study using an in-vivo rat model revealed that intravenous dopamine prevents DF and simultaneously increases diaphragm blood flow and, hence, oxygen delivery to the tissue. It is also possible that dopamine prevents DF, independent of its effect on oxygen delivery, through diaphragm muscle dopaminergic receptors, beta-2 adrenoceptors and through calcium channels. While holding oxygen delivery constant during in-vitro experiments, we observed that administering dopamine improved diaphragm muscle contraction. The goal of this project is to delineate the physiologic, cellular and biochemical changes in DF and the mechanisms accounting for the alleviation of DF by dopamine. We propose to determine whether 2 markers of oxidative damage, deoxyribonucleic acid (DNA) damage and glutathione oxidation, in the fatigued diaphragm and the effects of dopamine on these markers. We will perform a series of in-vitro experiments producing DF by electrical stimulation. After determining the optimal concentration of dopamine in the tissue bath to treat DF, class specific antagonists (butaclamol - Dopamine 1 (DA1) and a Dopamine 2 (DA2) antagonist; SCH 23390 - DA1 antagonist; domperidone - DA2 antagonist; ICI 118,551beta-2 antagonist; and verapamil - calcium channel blocker) will be administered with dopamine to determine the mechanisms by which dopamine affects diaphragm muscle contraction. The results will indicate if dopamine directly affects oxidative damage and diaphragm performance. Data obtained from this research will advance our understanding of biological systems, and thus provide data to support clinical trials using dopamine to prevent and treat DF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE HOMEOSTASIS, VESICLES & NEURODEGENERATION Principal Investigator & Institution: Sonsalla, Patricia K.; Professor of Neurology; Neurology; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 08854 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) Parkinson's disease is a debilitating motor impairment disorder due to loss of nigral dopamine neurons. Mitochondrial defects in PD patients implicate energy impairment and metabolic stress as potential factors in its etiology. Moreover, DA oxidation products may add to the oxidative burden within DA neurons which, coupled with a persistent metabolic stress, may lead to neurodegeneration. Epidemiological studies link PD with environmental exposure to substances such as pesticides. - Many pesticides are mitochondrial inhibitors. A potential form of protection against mitochondrial toxins (i.e., MPP+) may be their sequestration into synaptic vesicles of DA neurons. The goal of this project is to gain an understanding of the role of vesicles, the vesicular monoamine transporter (VMAT2) and DA in modulating neurodegeneration produced by mitochondrial toxins. One hypothesis is that the actions of mitochondrial toxins can be modulated in contrasting ways depending on whether the toxins are sequestered into vesicles. If sequestered, toxin exposure could be abrogated. In contrast, disruption of vesicular function toxin could lead to disturbed DA homeostasis and enhanced toxicity since it would remove the toxin from interaction with mitochondria. In Aim 1 several mitochondrial toxins will be examined for their ability to interfere with vesicle function (i.e. to inhibit DA uptake into isolated rat membrane vesicles). In aim 2, rat mesencephalic cultures or rat striata will be exposed to mitochondrial toxins following VMAT2 inhibition to determine if toxicity is modified. To examine the hypothesis that disturbed DA homeostasis contributes to degeneration produced by metabolic stress, two approaches will be used. First, DA will be depleted prior to exposure of culture or rat striata to a mitochondrial inhibitor. Second, vesicle contents (DA) will be released into the cytosol after exposure to the mitochondrial toxin to examine if augmented disruption of DA homeostasis during the metabolic stress enhances toxicity. Additionally, the hypothesis that substances that are not themselves mitochondrial inhibitors, but can disrupt DA storage in vesicles may amplify damage during episodes of metabolic stress will be examined in Aim 3. In aim 4 the hypothesis that early events such as oxidative stress leads to loss of vesicle function, disruption of DA homeostasis and exacerbation of neurodegeneration produced by toxins will be investigated. Isolated vesicles will be tested for their sensitivity to oxidizing and reducing conditions. Results from these studies will provide novel and relevant information as to the contribution of VMAT2 containing vesicles in neuroprotection as well as in neurodegeneration of DA neurons during metabolic stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENHANCE EFFECTIVENESS OF ANTI-HIV DRUGS IN THE CNS Principal Investigator & Institution: Unadkat, Jashvant D.; Professor; Pharmaceutics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 21-SEP-2001; Project End 31-AUG-2004 Summary: (Provided by applicant) A larger and more ambitious application on this topic was submitted as an ROl in response to an RFA from NIMH on "Impact of HAART on HIV/CNS diseases." In response to the major criticism of the reviewers, that of lack of preliminary data, we have revised and reduced the scope of the application to meet the specifications of an R2 1 application. An R2 1 application is specifically
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targeted to allow generation of preliminary data. Neurological complications are the most frequent and detrimental quality of life problems experienced by people with HWinfection. The initial pathogenic step in HIV-associated neurocognitive disorders is the establishment of replicative HIV infection in the brain. Thus, lowering CNS viral burden should provide effective therapy for neurocognitive disorders. However, this goal is compromised by the fact that the exposure of the CNS to the antiretroviral drugs is restricted by active efflux of these drugs by various transporters located at the bloodbrain and blood/CSF barrier. In animal studies, the efflux of the antiretroviral drugs, protease inhibitors, from the CNS has been shown to be mediated by the efflux pump, P-glycoprotein (P-gp). Therefore, we have hypothesized that inhibition of P-gp should result in enhanced concentrations of these drugs in CNS and therefore more effective therapy for prevention and treatment of HI V-associated neurocognitive disorders. Hypothesis Inhibition of P-gp increases the exposure of the CNS to protease inhibitors. The specific aims listed below use the state of the art izoninvasive and quantitative positron emission tomography (PET) techniques to test this hypothesis in hum an subjects Specific Aims: (a) To develop a reliable, validated protocol for synthesis of l"CJverapainil (a P-gp substrate) for IV administration to human subjects. (b) To obtain the necessary l"cJ-verapamil dosimetry, imaging and pharmacokinetic data jn human subjects (n=3) to gain local regulatory approval for studies outlined under specific aim. To test our hypothesis, using PET, that inhibition of P-gp in creases the exposure of CNS to l"1CJ-verapamil and, by inference, protease inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERTENSION PHARMACOGENETICS Principal Investigator & Institution: Johnson, Julie A.; Professor and Chair, Pharmacy Practice; Pharmacy Practice; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Hypertension (HTN) is the most common chronic disease in the United States, and is a leading cause of stroke, acute myocardial infarction (MI), heart failure and kidney failure. There are numerous effective antihypertensive drug classes, but only about half of patients have a good response to any given drug. Pharmacogenetics might significantly improve BP control and outcomes, as geneticallyguided drug therapy selection could dramatically increase the number of patients who receive the best drug for their HTN. We propose to test pharmacogenetic hypotheses that center on BP response and outcomes (death, MI, stroke) in HTN, using 5,871 genomic DNA samples we have collected from participants in INVEST, a large, international trial in patients with HTN and ischemic heart disease. We propose to test the following hypotheses: Hypothesis 1: Genetic variability in the proteins important to verapamil's pharmacologic action contribute to interpatient variability in verapamil's antihypertensive effect. Specific Aim 1A. Identify sequence variability in the genes for the major L-type Ca channel (LTCC) subunits alpha1C and beta, the sarcoplasmlc retlculum Ca2+-ATPase 2, the Ca2+-activated K channel, and critical portions of the ryanodine receptor by resequencing the genes in Corriel DNA from 60 individuals. Predict those polymorphisms most likely to be functionally significant using various bioinformatics techniques. Specific Aim lB. Perform in vitro functional studies, including ion channel patch-clamp studies, to test for functional significance of polymorphisms in the LTCC a1C subunit. Specific Aim 1C. Determine the association between verapamil's antihypertensive effect and genetic polymorphisms of interest, as identified in Aim 1A. Hypothesis 2: Antihypertensives that target the underlying molecular/genetic basis of a patient's HTN will result in better outcomes than
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antihypertensives that do not target the underlying pathophysiology. Specific Aim 2. Determine whether drug therapy that is targeted at a "drug response" polymorphism or haplotype results in better patient outcomes (specifically fewer deaths, strokes, MIs) than therapy that does not target the "drug response" polymorphism(s). This hypothesis will be tested for all four study drugs: atenolol, verapamil, hydrochlorothiazide and trandolapril. Because of the diversity of the INVEST genetics sample (47% Hispanic (mostly Puerto Ricans), 38% Caucasian and 11% African American), we will test Hypothesis 3: Use of molecular markers to define genetic heterogeneity in the study population is superior to race/ethnicity information in genetic associations with drug response. Specific Aim 3A. Determine whether models of genetic association with drug response perform better with use of genetic marker-defined population cluster and individual ancestral proportion information than with clinician-defined information on race/ethnicity. Specific Aim 3B. Document that any positive associations between drug response and genotype are not the result of population stratification or admixture. These aims will be accomplished by genotyping patients for at least 50 Ancestral Informative Markers. The proposed studies will provide considerable new evidence regarding the pharmacogenetics of verapamil, and will significantly further our understanding of the pharmacogenetics of p-blockers, thiazide diuretics, and ACE inhibitors. They will substantially enhance our understanding of the genetic variability in proteins important to Ca ++ regulation and response to CCBs and other drugs, and the functional significance of this genetic variability. Finally, the proposed studies will increase our understanding of the role of molecular markers for defining population stratification and admixture in pharmacogenetic studies. The proposed studies should add substantial new information about antihypertensive pharmacogenetics, and could influence how antihypertensive medications are prescribed in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECH WHICH 5HT MOBILIZES CALCIUM TO ENHANCE CONTRACTILITY OF VENTRICULAR MUSCLE Principal Investigator & Institution: Devlin, C L.; Marine Biological Laboratory 7 Mbl St Woods Hole, Ma 02543 Timing: Fiscal Year 2002 Summary: Molluscan hearts are modulated by numerous cardioexcitatory agents such as the neuropeptide FMRFamide and neurotransmitter, 5-hydroxytryptamine (5HT). The current project, using as the primary technique self-referencing calcium electrodes, studied mechanisms by which 5HT mobilizes calcium from various cellular compartments to enhance the contractility of ventricular muscle. Treatment of isolated muscle bundles, trabeculae, from the inner wall of the gastropod ventricle with micromolar concentrations of 5HT caused transient calcium efflux. This efflux was probably the result of a previous influx of calcium through L-type calcium channels and reflects rapid extrusion mechanisms by the sarcolemma of the cardiac myocytes. A similar effect has been previously described in the cardiac preparation in response to FMRFamide (Devlin, 1997). However, there are pronounced differences between the efflux stimulated by 5HT and that of FMRFamide. 5HT-induced efflux was typically a small, short-lived transient, whereas FMRFamide caused not only a more sustained efflux but it was of larger magnitude. To test the hypothesis that calcium was first entering through voltage-gated L-type channels, verapamil (a calcium channel blocker) and Bay K 8644 (a channel agonist) were tested. Neither verapamil nor Bay K 8644 had any effect on spontaneous efflux. Verapamil however inhibited calcium efflux stimulated by 5HT, whereas Bay K 8644 potentiated the efflux. These data corroborate
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earlier findings (Devlin, 1997) that found invertebrate muscle to be sensitive to mammalian L-type channel, and is further evidence in support of a use-dependent mechanism by calcium channel drugs. A Na+-free, lithium-substituted saline, or benzamil, were used to study the role of the Na/Ca exchanger in calcium efflux. Treatment of the trabeculae with a Na+-free, lithium-substituted saline had no effect on spontaneous calcium efflux, but greatly inhibited 5HT-induced efflux. Benzamil caused a sustained calcium influx that was slightly potentiated by simultaneous treatment with 5HT. Treatment of the trabeculae with cyclopiazonic acid, an inhibitor of the SR calcium ATPase, completely eliminated any calcium efflux stimulated by 5HT. This data suggests that 5HT may use the SR as its' primary calcium reservoir during the process of E-C coupling in this muscle. Devlin, C.L. 1997. A vibrating Ca2+-selective electrode measures Ca2+ flux induced by the neuro-peptide FMRFamide in a gastropod ventricle. Comp. Biochem. Physiol. 116A: 93-100. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF ATP DEPENDENT TRANSPORT BY MRP1 PROTEIN Principal Investigator & Institution: Chang, Xiu-Bao; Mayo Clinic Coll of Med, Mayo Clinic Az Sc Johnson Research Medical Building Scottsdale, Az 85259 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: Overexpression of P-glycoprotein (P-gp) and/or multidrug resistanceassociated protein (MRP1) is associated with resistance of tumors to a wide range of chemotherapeutic drugs. Many cancers initially respond well to chemotherapeutic treatment, but these tumors eventually become resistant to those cytotoxic drugs. Some other cancers are resistant to anticancer drugs, even at the beginning of treatment. Therefore, no matter whether the resistance is "acquired" or "intrinsic," multidrugresistance is one of the major obstacles to the successful treatment of many types of cancers. The mechanism of multidrug resistance conferred by either P-gp or MRP1 involves extrusion of the drugs out of the tumor cells. Both P-gp and MRP1 are members of the ABC superfamily of transport proteins, typically containing two membrane-spanning domains and two nucleotide binding domains. However, MRP1 differs from P-gp in that it contains an extra membrane-spanning domain at the Nterminus. ATP (binding and hydrolysis) is required in both cases. However, the transport steps differ in that P-gp extrudes the unmodified drugs directly, while the drugs transported by MRP1 protein require the presence of a hydrophilic compound, e.g., glutathione- or glucuronide-conjugates. Since the mechanism of multidrug resistance conferred by P-gp or MRP1 is to reduce the level of drug accumulation inside of the cell, inhibiting of the function of P-gp or MRP1 may reverse the drug resistance. Therefore, much effort is being devoted to discover specific inhibitors of these pumps. Present candidates as modulators of the process include verapamil, cyclosporin A, Cremophor, ardeemins, PSC833, rifamycins, RU486, MS-209, non-steroidal inflammatory drugs, acrolein, pyridine analogues, ONO-1078, chloroacetaldehyde, imidazothiazole derivatives, and even some protein kinase inhibitors. However, in order to develop well-designed specific modulators, it is important to understand the mechanisms of drug transport carried out by each individual protein. The first specific aim is to further characterize the ATP finding/hydrolysis and substrate transport by MRP1 protein. The second aim is to determine whether MRP1 protein phosphorylates itself or is a substrate for other protein kinases. This is based on our hypotheses that the phosphorylated MRP1 protein is an intermediate (i.e., there is an autophosphorylation) during ATP hydrolysis and substrate transport. The third aim is to define the substrate
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binding site(s). New insights gained from these aims should provide the basis for novel means of combating multidrug resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OLDER PERSONS AND DRUGS--RACE, GENDER, AND AGE EFFECTS Principal Investigator & Institution: Schwartz, Janice B.; Director; Goldman Institute on Aging 3330 Geary Blvd, 2Nd Fl San Francisco, Ca 94118 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 30-JUN-2004 Summary: (adapted from Investigator's abstract) It is stated that most clinical pharmacology studies in older persons have included small numbers of individuals who were healthy, under 70 to 75 years and were white. This application seeks to extend the study of age related pharmacokinetics and drug metabolism to include older persons, frail individuals, males and females, and minorities. Furthermore, it is proposed to examine the effect of diet on drug metabolism and clearance. The proposal has the following aims: 1) To determine the effects of race, gender, frailty, drug coadministration and diet on drug clearance in patients using population kinetic techniques. This will address numerous hypotheses including: a) That clearance of high first pass CYP3A substrate drugs such as verapamil and nifedipine but not amlodipine (multiple CYP pathway substrate with low clearance and low first pass metabolism) is decreased in African Americans compared to Caucasians; and b) Hypotheses related to effects of gender, clinical frailty (defined), other drugs and dietary intake will be tested in patients from outpatient clinics and extended care institutions. About 350 patients on each drug, with at least 100 subjects being frail, homebound or institutionalized, will be included. Extensive data will be collected in a systematic fashion from the subjects, including detailed dietary history. Blood sampling will be performed 2 - 12 h after dose for estimation of plasma concentrations of nifedipine, verapamil, norverapamil, and amlodipine by HPLC and GC/ECD. Protein binding will be performed using equilibrium dialysis. Population kinetics will be performed using NONMEM analysis with age, gender, frailty and other covariates added in stepwise fashion. 2) To determine the mechanism for race and gender differences in drug clearance. Traditional methods will be used to address the following hypotheses: a) Race affects oral but not iv clearance of nifedipine and verapamil due to effects of self selected diet in African American and Caucasian men and women; b) That standard diet thus will eliminate differences; c) That gut metabolism is the reason for racial differences (abolished by CYP3A gut inhibition) in bioavailability but not gender (not abolished by CYP3A gut inhibition) differences; d) Gender differences reflect higher hepatic and intestinal clearance in females; and e) Ethnic differences are related to diet and abolished by standard diet. Pharmacokinetic studies will be performed in young and older, healthy male and female, white and African American volunteers. Individuals will be given iv an oral nifedipine and verapamil under controlled conditions and blood sampling will be performed for drug/metabolite assays and pharmacokinetic analysis. As much as possible the same subjects will have oral pharmacokinetic studies of nifedipine and verapamil performed following grapefruit juice to block intestinal CYP3A. Further studies are planned to compare oral pharmacokinetics of verapamil and/ nifedipine in similar subjects on a standardized diet. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPLICATIONS
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Principal Investigator & Institution: Pollack, Gary M.; Professor and Chair; Drug Delivery & Disposition; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's abstract): Transport by P-glycoprotein (P-gp) is an important determinant of disposition for numerous pharmacological agents. A significant body of evidence has shown that decreases in P-gp activity can increase drug absorption from the GI tract, decrease drug/metabolite excretion in the liver and/or kidney, and enhance distribution of parent drug/active metabolites to target organs (e.g., the CNS) or pharmacologically relevant intracellular sites (e.g., leukocytes). Although the potential for induction of P-gp is well documented in the cancer chemotherapy literature, the implications of P-gp induction on the systemic disposition and pharmacological activity of P-gp substrates has yet to be addressed. Recent work in this laboratory has demonstrated that morphine is a substrate for P-gp-mediated transport, that alterations in P-gp activity influence morphine disposition and action and that morphine administration in vivo increases the P-gp content in rat brain. These observations are particularly important from a clinical perspective because of the key role of morphine in management of pain associated with cancer and other diseases requiring chronic analgesia. Therapeutic agents (e.g., anticancer drugs) that increase Pgp activity may decrease the efficacy of morphine in these patients. Conversely, induction of P-gp by morphine may limit the activity of other P-gp substrates. The long term objective of this research program is to explore the hypothesis that inducers of Pgp cause clinically relevant alterations in the disposition and action of P-gp substrates. The proposed project will utilize a multi-experimental approach to address the hypotheses that: 1) extent of P-gp induction in specific organs is a function of inducer potency and inducer concentration, 2) perturbations in the kinetics of a P-gp substrate can be predicted based on the degree of P-gp induction in organs/tissues, and 3) P-gp induction in humans can result in clinically significant alterations in the systemic disposition and action of P-gp substrates. In addressing these hypotheses, P-gp induction will be assessed in vitro in cultured hepatocytes (rat and human) and in vivo in selected organs, the impact of P-gp induction on drug disposition will be evaluated in isolated organ systems, and the implications of P-gp induction on systemic pharmacokinetics and pharmacodynamics will be examined in rats and humans. The potential importance of this research becomes apparent when one considers the number of therapeutic agents that are substrates of P-gp, the location of P-gp in organs of kinetic/dynamic importance, and the likelihood that numerous therapeutic, dietary, and environmental agents may modulate the activity of P-gp. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGICAL TREATMENT OF ETHANOL WITHDRAWAL Principal Investigator & Institution: Gonzalez, Larry P.; Professor; Psychiatry and Behavioral Scis; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 30-JUN-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PULMONARY UPTAKE AND KINETICS OF IV ANESTHETICS Principal Investigator & Institution: Henthorn, Thomas K.; Associate Professor and Director of Rese; Anesthesiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-MAY-1992; Project End 29-SEP-2004 Summary: (Adapted from the abstract) The investigators have demonstrated that fentanyl and verapamil are substrates of two distinct transporters at the blood-brain barrier: an efflux transporter, P-glycoprotein (P-gp), and an unidentified uptake transporter. The proposed work will study the pharmacology of these endothelial mechanisms. Kinetic studies using cultured endothelial cells derived from lung and brain will investigate the extent to which the partitioning of opioid anesthetic drugs into or away from these tissues is mediated by drug transporters, and what drugs or factors influence them. Isolated perfused rat lung studies will be conducted to determine the contribution of the lung tissue matrix to the pharmacokinetics of drug distribution, and to further validate models of pulmonary uptake developed as part of the in vivo recirculatory pharmacokinetic models. Pharmacokinetic-pharmacodynamic studies of CNS effects of synthetic opioid drugs will be performed in an in vivo rat EEG paradigm and correlated to analgesia. Treatment will consist of blockade of either endothelial drug uptake or efflux functions. These experiments will describe any changes in the speed of onset and offset of drug effect and the sensitivity of the brain to opioid due to changes in drug transporter function. These experiments are designed to differentiate changes in pharmacokinetics produced by transporter blockade in the body as a whole (specifically the lung) from changes at the brain effect site. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PFCRT IN CHLOROQUINE RESISTANCE IN P. FALCIPARUM Principal Investigator & Institution: Fidock, David A.; Assistant Professor; Microbiology and Immunology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2006 Summary: (provided by the applicant): The emergence and spread of chloroquine resistant (CQR) strains of Plasmodium falciparum, first reported in Asia and South America, drastically compromises efforts to treat and control malaria. Chloroquine (CQ) interferes with the process of heme polymerization in the parasite digestive vacuole (DV) and chloroquine resistance (CQR) is associated with reduced accumulation of this drug. Our long-term objective is to understand CQR at the genetic and physiological level. Recent work has led to the identification of the pfcrt (P. falciparum chloroquine resistance transporter) gene, which encodes the DV transmembrane protein PfCRT. Mutations in pfcrt segregate with the verapamil (VP)-reversible CQR phenotype in a genetic cross and show a strong association with CQR in laboratory-adapted field isolates. These data and CQ selection experiments implicate a central role for pfcrt mutations in CQR. This now raises the critical question of whether CQR results from mutations in this gene alone or whether multiple genes are necessary for this phenotype. Significant insight into the CQR mechanism can also now be gained by defining the physiological function(s) of PfCRT. The first specific aim of this application is to assess the contribution of individual pfcrt mutations to CQR. Chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) P. falciparum lines will be transformed with episomal transgene constructs that express pfcrt sequences from CQR and CQS parasites and transformed lines will be assayed for changes in parasite response to CQ+/-VP. These
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assays provide a rapid screen to identify key pfcrt mutations involved in CQR. The second specific aim will determine by allelic exchange whether pfcrt mutations are necessary and sufficient to confer P. falciparum CQR in both New and Old World strains. The third specific aim will determine the physiological function of PfCRT and how this relates mechanistically to CQR. Single-cell pH measurements on pfcrfmodified lines will be performed to test the model that pfcrt mutations can cause CQR by acidification of the DV pH. pfcrt sequences will be expressed in Xenopus laevis oocytes to assess for transport of CQ and candidate physiological substrates. These studies will yield data that should stimulate new strategies to counter the spread of CQR malaria and contribute significantly to understanding the molecular and physiological basis of CQR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RYANODINE RECEPTOR DYSFUNCTION IN DIABETIC HEARTS Principal Investigator & Institution: Bidasee, Keshore R.; Pharmacology and Toxicology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 30-SEP-2002 Summary: Applicant's Abstract Release of calcium ions from the sarcoplasmic reticulum via type 2 ryanodine receptors (RyR2) is an integral step in the cascade of events leading to cardiac muscle contraction. Studies have shown that this process is compromised in heart of diabetic rats (Yu and McNeill 1991; Yu et al. 1994). We recently found that the decrease in activity of RyR2 stems from a dysfunction of this protein rather than a decrease its expression (Bidasee et al manuscript #1). To date, the molecular basis for the dysfunction of RyR2 is not known. Our working hypothesis is "diabetes alters the integrity of the calcium efflux pathway on RyR2." In this project we want to characterize changes in RyR2 induced by diabetes and to determine the effects of these changes on the regulation of RyR2 by endogenous modulators. At the same time, we want to investigate whether the beneficial effects of insulin and verapamil treatments include reversal of diabetes-induced changes to RyR2 protein. Our specific aims are: (1) to identify and characterize molecular changes to RyR2 protein induced by diabetes, (2) to ascertain whether these changes alter the sensitivity of RyR2 to endogenous modulators like Ca2+, pH etc., (3) to determine whether changes to RyR2 induced by long-term diabetes can be reversed with insulin treatment, (4) to determine whether verapamil treatment can protect and/or reverse diabetes-induced changes to RyR2, and (5) to establish if verapamil and insulin co-treatments have additive effects on reversing changes to RyR2 induced by diabetes. Accomplishment of these aims will contribute significantly to understanding the molecular basis for the decrease activity of RyR2 protein (and possibly other proteins) in diabetes and this could lead to newer insights into therapeutic strategies for alleviating diabetes-induced dysfunction of the heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: WALKING ADHERENCE AND HEALTH IN AFRICAN AMERICAN WOMEN Principal Investigator & Institution: Wilbur, Joellen; Professor; Pub Hlth/Mental Hlth/Admin Nur; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAY-2005
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Summary: (provided by applicant): The purpose of this study is to test the efficacy of a 48-week home-based walking intervention for low-income midlife (45-65 years) African American (AA) women. The intervention is enhanced by behavior strategies tailored to a woman's community and personal characteristics (Enhanced treatment). The specific aims are (1) to describe the changes in adherence-enhancing factors (social influence, interpersonal characteristics-cognition, attitude and motivation) and health-status outcomes (cardiovascular [CV] health and symptoms) for both the Enhanced Treatment (ET) and a Standard Treatment (ST) without the behavioral strategies at baseline, 24, 48, and 72 weeks; (2) to compare women receiving the ET to the women in the ST on adherence-enhancing factor, exercise adherence indicators (frequency, duration, and intensity of exercise; patterns of adherence; energy expenditure) and health status at 24, 48 and 72 weeks; (3) to identify the relationships among adherence-enhancing factors, exercise adherence indicators, and health -status outcomes. The ET will be randomly assigned to one of two health centers in the Chicago Westside where heart disease is among the highest in the city. Subjects will include 240 sedentary women who have no major signs or symptoms of CV disease; no history of myocardial infarction, stroke, or Type 1 diabetes; and are not on a beta blocker, Ditiazem or Verapamil. Women will be recruited from low-income communities surrounding the two health centers. Women (both treatments) will be oriented to the walking prescription, which is moderate intensity, a minimum of three 30-minute sessions per week. During the 24-week active phase, the ET receives a combined behavioral package of community-focused strategies delivered by community workers via workshops tailored to the women's environmental characteristics, and individually-focused strategies delivered via phone tailored to each women's personal characteristics. During the 24-week maintenance phase, women in the ET receive phone calls monthly or bimonthly, depending on their adherence. Both treatment groups will self-monitor their performance with heart rate monitors, enter exercise-log data via a voice response system, and have three face-to-face visits with the community worker during each phase. During the 24-week follow-up phase, neither group receives behavior strategies. The Physical Activity Behavior Framework, derived from Cox's Interaction Model of Client Health Behavior, will guide the intervention. Analyses include descriptive statistics, change scores, and mixed-effects regression models for the longitudinal data. 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 “verapamil” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for verapamil in the PubMed Central database: 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Autoradiographic method for measuring the ischemic myocardium at risk: effects of verapamil on infarct size aftr experimental coronary artery occlusion. by DeBoer LW, Strauss HW, Kloner RA, Rude RE, Davis RF, Maroko PR, Braunwald E.; 1980 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350225
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Combined Effect of Glucose and Verapamil in Experimental Cardioplegia. by Hochhauser E, Barak Y, Einav S, Cohen S, Vidne B.; 1986 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324599
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Hypertrophic Obstructive Cardiomyopathy: Hemodynamic Improvement with Intravenous Verapamil. by Roth SJ, Porter CB, Latson LA.; 1983 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341633
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In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine), quinine sulfate, mefloquine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii. by Holfels E, McAuley J, Mack D, Milhous WK, McLeod R.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188216
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Manipulation of the N-alkyl substituent in amodiaquine to overcome the verapamilsensitive chloroquine resistance component. by Hawley SR, Bray PG, O'Neill PM, Naisbitt DJ, Park BK, Ward SA.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163532
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Photoaffinity labeling of the multidrug-resistance-related P-glycoprotein with photoactive analogs of verapamil. by Safa AR.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282149
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Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine. by Warhurst DC.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=269985
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The Detergent-Soluble Maltose Transporter Is Activated by Maltose Binding Protein and Verapamil. by Reich-Slotky R, Panagiotidis C, Reyes M, Shuman HA.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94375
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Verapamil Restoration of Daunorubicin Responsiveness in Daunorubicin-resistant Ehrlich Ascites Carcinoma. by Slater LM, Murray SL, Wetzel MW, Wisdom RM, Duvall EM.; 1982 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370327
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Verapamil-Potassium Cardioplegia: A Two-Year Experience with 470 Patients. by Hicks GL Jr.; 1986 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=324600
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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 verapamil, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “verapamil” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for verapamil (hyperlinks lead to article summaries): •
A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. Author(s): Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, Mancia G, Cangiano JL, Garcia-Barreto D, Keltai M, Erdine S, Bristol HA, Kolb HR, Bakris GL, Cohen JD, Parmley WW; INVEST Investigators. Source: Jama : the Journal of the American Medical Association. 2003 December 3; 290(21): 2805-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657064
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A comparative trial of controlled-onset, extended-release verapamil, enalapril, and losartan on blood pressure and heart rate changes. Author(s): Bakris G, Sica D, Ram V, Fagan T, Vaitkus PT, Anders RJ. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 January; 15(1 Pt 1): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11824861
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A comparison of the modulation of antiblastics cytotoxicity by verapamil and dipyridamole in a human colon carcinoma cell line. Author(s): Berti E, Carrara M, Ragazzi E, D'Ancona S, Berti T. Source: International Journal of Oncology. 1999 July; 15(1): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10375609
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A mixed-drug intoxication involving venlafaxine and verapamil. Author(s): Kunsman GW, Kunsman CM, Presses CL, Garavaglia JC, Farley NJ. Source: J Forensic Sci. 2000 July; 45(4): 926-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914601
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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 new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning. Author(s): Smith DH, Neutel JM, Weber MA. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 January; 14(1): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11206672
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A randomized prospective double-blind placebo-controlled study of gallopamil, calcium antagonist of the verapamil type, in stable cyclosporine-treated renal transplant recipients. Author(s): Gossmann J, Mondorf U, Dietz A, Kramer W, Kachel HG, Geiger H, Scheuermann EH. Source: Transplantation Proceedings. 2002 August; 34(5): 1767-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12176568
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A steady-state evaluation of the bioavailability of chronotherapeutic oral drug absorption system verapamil PM after nighttime dosing versus immediate-acting verapamil dosed every eight hours. Author(s): Prisant LM, Devane JG, Butler J. Source: American Journal of Therapeutics. 2000 November; 7(6): 345-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11304641
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A validated method for the determination of verapamil and norverapamil in human plasma. Author(s): Sawicki W. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 June; 25(3-4): 689-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377051
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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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Achiral and chiral high-performance liquid chromatography of verapamil and its metabolites in serum samples. Author(s): Brandsteterova E, Wainer IW. Source: J Chromatogr B Biomed Sci Appl. 1999 September 24; 732(2): 395-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10517362
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Adaptive response towards adriamycin in vitro: circumvention with verapamil. Author(s): Anuszewska EL, Koziorowska JH. Source: Mutation Research. 1999 December 16; 431(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10656483
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Adenosine- and verapamil-sensitive ventricular tachycardia in the newborn. Author(s): Ozer S, Allen S, Schaffer MS. Source: Pacing and Clinical Electrophysiology : Pace. 2001 May; 24(5): 898-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11388113
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Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. Author(s): Neuhoff S, Langguth P, Dressler C, Andersson TB, Regardh CG, SpahnLangguth H. Source: Int J Clin Pharmacol Ther. 2000 April; 38(4): 168-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10783826
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Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism. Author(s): Xu B, Xiao-hong L, Lin G, Queen L, Ferro A. Source: British Journal of Pharmacology. 2002 June; 136(3): 375-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023940
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An autopsy case of combined drug intoxication involving verapamil, metoprolol and digoxin. Author(s): Kinoshita H, Taniguchi T, Nishiguchi M, Ouchi H, Minami T, Utsumi T, Motomura H, Tsuda T, Ohta T, Aoki S, Komeda M, Kamamoto T, Kubota A, Fuke C, Arao T, Miyazaki T, Hishida S. Source: Forensic Science International. 2003 April 23; 133(1-2): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742696
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Angina pectoris, myocardial infarction and verapamil. Author(s): Hansen JF, Mellemgaard K. Source: Journal of the American College of Cardiology. 1999 September; 34(3): 957-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10483985
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Antihypertensive therapy with verapamil SR plus trandolapril versus atenolol plus chlorthalidone on glycemic control. Author(s): Holzgreve H, Nakov R, Beck K, Janka HU. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2003 May; 16(5 Pt 1): 381-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12745200
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Antiproteinuric efficacy of verapamil in comparison to trandolapril in non-diabetic renal disease. Author(s): Hemmelder MH, de Zeeuw D, de Jong PE. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 January; 14(1): 98-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10052485
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Attenuation of electrical remodelling in chronic atrial fibrillation following oral treatment with verapamil. Author(s): Meurling CJ, Ingemansson MP, Roijer A, Carlson J, Lindholm CJ, Smideberg B, Sornmo L, Stridh M, Olsson SB. Source: Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology. 1999 October; 1(4): 234-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11220560
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Azacytidine plus verapamil induces the differentiation of a newly characterized biphenotypic human myeloid-B lymphoid leukemic cell line BW-90. Author(s): Zinzar S, Silverman LR, Richardson EB, Bekesi G, Holland JF. Source: Leukemia Research. 1998 August; 22(8): 677-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9680094
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Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. Author(s): Taniyama Y, Ito H, Iwakura K, Masuyama T, Hori M, Takiuchi S, Nishikawa N, Higashino Y, Fujii K, Minamino T. Source: Journal of the American College of Cardiology. 1997 November 1; 30(5): 1193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9350914
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Beneficial effect of intrarenal verapamil in human acute renal failure. Author(s): Lumlertgul D, Hutdagoon P, Sirivanichai C, Keoplung M, Wongmekiat O, Nitsin S, Sangchun G. Source: Renal Failure. 1989-90; 11(4): 201-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2485483
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Beneficial effect of oral verapamil on exercise induced silent myocardial ischemia. Author(s): Bajaj R, Kaul U, Malhotra A, Gopinath P, Bhatia ML. Source: Indian Heart J. 1989 March-April; 41(2): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2744801
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Beneficial effect of verapamil added to chronic ACE inhibitor treatment on renal function in hypertensive elderly patients. Author(s): Bitar R, Flores O, Reverte M, Lopez-Novoa JM, Macias JF. Source: International Urology and Nephrology. 2000; 32(2): 165-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11229627
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Beneficial effects of verapamil in renal transplantation. Author(s): Erken U, Erken E, Tansug Z, Bayazit Y, Isik G, Turkyilmaz R. Source: Transplantation Proceedings. 1993 June; 25(3): 2187. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8516864
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Beneficial effects of verapamil in renal-risk surgical patients. Author(s): Tataranni G, Malacarne F, Farinelli R, Tarroni G, Gritti G, Guberti A, Tartari S, Zavagli G. Source: Renal Failure. 1994; 16(3): 383-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8059021
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Bepridil versus verapamil in stable angina pectoris--a controlled clinical trial. Author(s): Nielsen HK, Krusell LR, Husted SE, Pluymers RJ. Source: International Journal of Cardiology. 1989 June; 23(3): 357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2500401
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Binding of an optically pure photoaffinity analogue of verapamil, LU-49888, to Pglycoprotein from multidrug-resistant human leukemic cell lines. Author(s): Qian XD, Beck WT. Source: Cancer Research. 1990 February 15; 50(4): 1132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1967551
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Bioavailability study of two different verapamil formulations. Author(s): Horne C, Stenzhorn G, Blume H, Knauf H, Mutschler E. Source: Archiv Der Pharmazie. 1992 August; 325(8): 531-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1417461
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Bioequivalence of verapamil hydrochloride extended-release pellet-filled capsules when opened and sprinkled on food and when swallowed intact. Author(s): Kozloski GD, De Vito JM, Johnson JB, Holmes GB, Adams MA, Hunt TL. Source: Clin Pharm. 1992 June; 11(6): 539-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1600686
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Bisoprolol in the treatment of angina pectoris: a double blind comparison with verapamil. Author(s): De Divitiis O, Liguori V, Di Somma S, Brignoli M, Ferraro S, Petitto M, Fazio S, Marsullo G, Salvatore M, Gradnik R. Source: European Heart Journal. 1987 December; 8 Suppl M: 43-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2967185
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Blocking of the receptor-stimulated calcium entry into human platelets by verapamil and nicardipine. Author(s): Avdonin PV, Men'shikov MYu, Svitina-Ulitina IV, Tkachuk VA. Source: Thrombosis Research. 1988 December 15; 52(6): 587-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3232128
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Blood pressure and aortic elastic properties--verapamil SR/trandolapril compared to a metoprolol/hydrochlorothiazide combination therapy. Author(s): Breithaupt-Grogler K, Gerhardt G, Lehmann G, Notter T, Belz GG. Source: Int J Clin Pharmacol Ther. 1998 August; 36(8): 425-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9726695
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Both lisinopril and verapamil reduced platelet-derived growth factor-A chain mRNA levels in human saphenous vein endothelial cells stimulated by thrombin. Author(s): Yamaguchi M, Gallati H, Baur W, Cruess DF, Sharefkin JB. Source: Surgery. 1994 April; 115(4): 495-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8165541
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Brachial plexus anesthesia with verapamil and/or morphine. Author(s): Reuben SS, Reuben JP. Source: Anesthesia and Analgesia. 2000 August; 91(2): 379-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10910852
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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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Calcium channel blockers, verapamil and cancer risk. Author(s): La Vecchia C, Bosetti C. Source: European Journal of Cancer (Oxford, England : 1990). 2003 January; 39(1): 7-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504652
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Can short-term verapamil therapy reduce the recurrence of atrial fibrillation after successful low energy intracardiac cardioversion? Author(s): Zardo F, Antonini-Canterin F, Brieda M, Hrovatin E, Pavan D, Burelli C, Cervesato E, Nicolosi GL. Source: Ital Heart J. 2001 July; 2(7): 513-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11501960
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Cardiogenic shock following a single therapeutic oral dose of verapamil. Author(s): Stajer D, Bervar M, Horvat M. Source: Int J Clin Pract. 2001 January-February; 55(1): 69-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11219325
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Cardiogenic shock triggered by verapamil and atenolol: a case report of therapeutic experience with intravenous calcium. Author(s): Sakurai H, Kei M, Matsubara K, Yokouchi K, Hattori K, Ichihashi R, Hirakawa Y, Tsukamoto H, Saburi Y. Source: Japanese Circulation Journal. 2000 November; 64(11): 893-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110438
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Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein. Author(s): Pauli-Magnus C, von Richter O, Burk O, Ziegler A, Mettang T, Eichelbaum M, Fromm MF. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 May; 293(2): 376-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10773005
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Chiral separation of verapamil and some of its metabolites by HPLC and CE. Author(s): Brandsteterova E, Endresz G, Blaschke G. Source: Pharmazie. 2001 July; 56(7): 536-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487971
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Chrono: a community-based hypertension trial of a chronotherapeutic formulation of verapamil. Author(s): Prisant LM, Black HR, Messerli F, Weber M. Source: American Journal of Therapeutics. 2002 November-December; 9(6): 476-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424503
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Chronotherapeutic delivery of verapamil in obese versus non-obese patients with essential hypertension. Author(s): White WB, Elliott WJ, Johnson MF, Black HR. Source: Journal of Human Hypertension. 2001 February; 15(2): 135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317194
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Circadian variations and chronotherapeutic implications for cardiovascular management: a focus on COER verapamil. Author(s): Glasser SP. Source: Heart Disease. 1999 September-October; 1(4): 226-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720629
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Combination of surgery and intralesional verapamil injection in the treatment of the keloid. Author(s): Copcu E, Sivrioglu N, Oztan Y. Source: The Journal of Burn Care & Rehabilitation. 2004 January-February; 25(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726733
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Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting. Author(s): Mussa S, Guzik TJ, Black E, Dipp MA, Channon KM, Taggart DP. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 December; 126(6): 1798-805. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688690
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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 the effect of verapamil and propranolol on response of coronary vasomotion to cold pressor test in symptomatic patients with hypertrophic cardiomyopathy. Author(s): Dimitrow PP, Krzanowski M, Nizankowski R, Szczeklik A, Dubiel JS. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2000 December; 14(6): 643-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300365
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Comparison of the vasodilating effect of nitroglycerin, verapamil, and tolazoline in hand angiography. Author(s): Stoeckelhuber BM, Suttmann I, Stoeckelhuber M, Kueffer G. Source: Journal of Vascular and Interventional Radiology : Jvir. 2003 June; 14(6): 749-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12817042
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Comparison of verapamil and ibutilide for the suppression of immediate recurrences of atrial fibrillation after transthoracic cardioversion. Author(s): Sticherling C, Ozaydin M, Tada H, Oral H, Pelosi F, Knight BP, Strickberger SA, Morady F. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2002 July; 7(3): 15560. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12232564
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Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients. Author(s): Petretta M, Canonico V, Madrid A, Mickiewicz M, Spinelli L, Marciano F, Vetrano A, Signorini A, Bonaduce D. Source: Journal of Hypertension. 1999 May; 17(5): 707-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403616
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Complete atrioventricular blockade secondary to conventional-release verapamil in a patient on hemodialysis. Author(s): Martin-Gago J, Pascual J, Rodriguez-Palomares JR, Marc n R, Teruel JL, Liano F, Ortuno J. Source: Nephron. 1999 September; 83(1): 89-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10461042
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Compound cardiac toxicity of oral erythromycin and verapamil. Author(s): Goldschmidt N, Azaz-Livshits T, Gotsman, Nir-Paz R, Ben-Yehuda A, Muszkat M. Source: The Annals of Pharmacotherapy. 2001 November; 35(11): 1396-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11724091
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Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension. Author(s): Lefrandt JD, Heitmann J, Sevre K, Castellano M, Hausberg M, Fallon M, Urbigkeit A, Rostrup M, Agabiti-Rosei E, Rahn KH, Murphy M, Zannad F, de Kam PJ, Smit AJ. Source: British Journal of Clinical Pharmacology. 2001 December; 52(6): 687-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736880
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Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis. Author(s): Mayo PR, Skeith K, Russell AS, Jamali F. Source: British Journal of Clinical Pharmacology. 2000 December; 50(6): 605-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11136300
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Defining the drug-binding site in the human multidrug resistance P-glycoprotein using a methanethiosulfonate analog of verapamil, MTS-verapamil. Author(s): Loo TW, Clarke DM. Source: The Journal of Biological Chemistry. 2001 May 4; 276(18): 14972-9. Epub 2001 February 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279063
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Definition of the reentry circuit with demonstration of a low frequency diastolic potential in a patient with verapamil-sensitive idiopathic left ventricular tachycardia. Author(s): Wen MS, Yeh SJ, Wu D. Source: Journal of Electrocardiology. 2002 October; 35(4): 357-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395364
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Deleterious effects of intravenous verapamil in Wolff-Parkinson-White patients and atrial fibrillation. Author(s): Strasberg B, Sagie A, Rechavia E, Katz A, Ovsyscher IA, Sclarovsky S, Agmon J. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1989 January; 2(6): 801-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2488095
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Demonstration of diastolic and presystolic Purkinje potentials as critical potentials in a macroreentry circuit of verapamil-sensitive idiopathic left ventricular tachycardia. Author(s): Nogami A, Naito S, Tada H, Taniguchi K, Okamoto Y, Nishimura S, Yamauchi Y, Aonuma K, Goya M, Iesaka Y, Hiroe M. Source: Journal of the American College of Cardiology. 2000 September; 36(3): 811-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987604
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Demonstration of the reentrant circuit of verapamil-sensitive idiopathic left ventricular tachycardia: direct evidence for macroreentry as the underlying mechanism. Author(s): Maruyama M, Tadera T, Miyamoto S, Ino T. Source: Journal of Cardiovascular Electrophysiology. 2001 August; 12(8): 968-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11513451
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Determination of verapamil by adsorptive stripping voltammetry in urine and pharmaceutical formulations. Author(s): Kasim EA, Ghandour MA, El-Haty MT, Ahmed MM. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 November 7; 30(4): 921-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408881
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Diastolic potentials in verapamil-sensitive ventricular tachycardia: true potentials or bystanders of the reentry circuits? Author(s): Sato M, Sakurai M, Yotsukura A, Betsuyaku T, Ito T, Yoshida I, Kitabatake A. Source: American Heart Journal. 1999 September; 138(3 Pt 1): 560-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10467209
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Difference in effects of alkyl-lysophospholipids and verapamil on vincristine transport in vincristine-sensitive and -resistant human myelogenous leukemia K562. Author(s): Tsuruo T, Saito H. Source: Anticancer Res. 1987 January-February; 7(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3471174
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Differences in response to single dose and steady-state therapy with verapamil in stable angina. Author(s): Vazquez de Prada JA, Zueco J, Ruano J, Martin-Duran R, Sanjose JM, Colman T, Pajaron A. Source: International Journal of Cardiology. 1991 September; 32(3): 339-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1791086
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Differential enantioselectivity and product-dependent activation and inhibition in metabolism of verapamil by human CYP3As. Author(s): Shen L, Fitzloff JF, Cook CS. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2004 February; 32(2): 186-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744940
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Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Author(s): Fromm MF, Busse D, Kroemer HK, Eichelbaum M. Source: Hepatology (Baltimore, Md.). 1996 October; 24(4): 796-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8855178
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Differential sensitivity of resting and IL-2 activated NK cells to R-verapamil. Author(s): Markham PN, Ellis TM, Tambur AR, Gebel HM. Source: Transplantation. 1996 December 27; 62(12): 1883-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990381
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Diltiazem, nifedipine, nimodipine or verapamil for neuroleptic-induced tardive dyskinesia. Author(s): Soares KV, McGrath JJ. Source: Cochrane Database Syst Rev. 2000; (2): Cd000206. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796323
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Disposition and pharmacologic effects of R/S-verapamil in patients with chronic atrial fibrillation: an investigation comparing single and multiple dosing. Author(s): Busse D, Fromm MF, Morike K, Drescher S, Kuhlkamp V, Eichelbaum M. Source: Clinical Pharmacology and Therapeutics. 2001 May; 69(5): 324-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11372000
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Divergent effects of verapamil and amlodipine at rest and during exercise. Author(s): Joannides R, Moore N, Iacob M, Compagnon P, Bacri AM, Thuillez C. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1998 January; 16(1): S25-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9534093
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Does verapamil act as an immunomodulatory drug in vivo? Author(s): Maisel AS, Murray D, Polizzi S, Motulsky HJ, Brodde OE, van Tits LJ, Michel MC. Source: Immunopharmacology. 1991 September-October; 22(2): 85-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1761403
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Does verapamil help overcome multidrug resistance in tumor cell lines and cancer patients? Author(s): Timcheva CV, Todorov DK. Source: J Chemother. 1996 August; 8(4): 295-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8873836
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Dose-dependent effects of intracoronary verapamil on systemic and coronary hemodynamics. Author(s): Oldenburg O, Eggebrecht H, Herrmann J, Naber CK, Haude M, Erbel R, Baumgart D. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2000 December; 14(6): 651-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300366
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Doxorubicin cellular pharmacokinetics plays no role in chemosensitizing effect of verapamil on Swiss-3T3 cells. Author(s): Wang N, Tang ZM, Zhang YP, Ding QM. Source: Zhongguo Yao Li Xue Bao. 1996 September; 17(5): 402-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9863159
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Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. Author(s): Ho PC, Ghose K, Saville D, Wanwimolruk S. Source: European Journal of Clinical Pharmacology. 2000 December; 56(9-10): 693-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11214778
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Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure. Author(s): Hung MJ, Cherng WJ, Kuo LT, Wang CH. Source: Int J Clin Pract. 2002 January-February; 56(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831838
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Effect of verapamil on immediate recurrence of atrial fibrillation. Author(s): Daoud EG, Hummel JD, Augostini R, Williams S, Kalbfleisch SJ. Source: Journal of Cardiovascular Electrophysiology. 2000 November; 11(11): 1231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11083244
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Effect of verapamil on prevention of atrial fibrillation in patients implanted with an implantable atrial defibrillator. Author(s): Tse HF, Wang Q, Yu CM, Ayers GM, Lau CP. Source: Clin Cardiol. 2001 July; 24(7): 503-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11450689
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Effect of verapamil on secondary cardioversion in patients with early atrial fibrillation recurrence after electrical cardioversion. Author(s): De Simone A, Turco P, De Matteis C, La Rocca V, Nocerino P, Greco L, Astarita C, Messina V, Rotunno R, Iaconelli G, Stabile E, Stabile G. Source: The American Journal of Cardiology. 2002 July 15; 90(2): 185-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12106857
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Effects of carvedilol on MDR1-mediated multidrug resistance: comparison with verapamil. Author(s): Kakumoto M, Sakaeda T, Takara K, Nakamura T, Kita T, Yagami T, Kobayashi H, Okamura N, Okumura K. Source: Cancer Science. 2003 January; 94(1): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12708479
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Effects of COER-verapamil on circadian pattern of forearm vascular resistance and blood pressure. Author(s): Nguyen BN, Parker RB, Noujedehi M, Sullivan JM, Johnson JA. Source: Journal of Clinical Pharmacology. 2000 December; 40(12 Pt 2): 1480-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11185670
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Effects of fosinopril or sustained-release verapamil on blood pressure and serum catecholamine concentrations in elderly hypertensive men. Author(s): Williams LS, Hill D, Davis J, Lowenthal DT. Source: American Journal of Therapeutics. 2000 January; 7(1): 3-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11319567
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Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Author(s): Fuhr U, Muller-Peltzer H, Kern R, Lopez-Rojas P, Junemann M, Harder S, Staib AH. Source: European Journal of Clinical Pharmacology. 2002 April; 58(1): 45-53. Epub 2002 March 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956673
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Effects of interferon-alpha, verapamil and dacarbazine in the treatment of advanced malignant melanoma. Author(s): Andersson R, Ake Hofer P, Riklund-Ahlstrom K, Henriksson R. Source: Melanoma Research. 2003 February; 13(1): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569290
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Effects of long-term treatment with verapamil on left ventricular function and myocardial blood flow in patients with dilated cardiomyopathy without overt heart failure. Author(s): Neglia D, Sambuceti G, Giorgetti A, Bartoli M, Salvadori P, Sorace O, Puccini G, L'Abbate A, Parodi O. Source: Journal of Cardiovascular Pharmacology. 2000 December; 36(6): 744-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11117374
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Effects of pretreatment with verapamil on early recurrences after electrical cardioversion of persistent atrial fibrillation: a randomised study. Author(s): Bertaglia E, D'Este D, Zanocco A, Zerbo F, Pascotto P. Source: Heart (British Cardiac Society). 2001 May; 85(5): 578-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11303016
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Effects of verapamil and ibutilide on atrial fibrillation and postfibrillation atrial refractoriness. Author(s): Sticherling C, Hsu W, Tada H, Bares AC, Oral H, Pelosi F, Knight BP, Strickberger SA, Morady F. Source: Journal of Cardiovascular Electrophysiology. 2002 February; 13(2): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11900290
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Effects of verapamil and lidocaine on two components of the re-entry circuit of verapamil-senstitive idiopathic left ventricular tachycardia. Author(s): Tsuchiya T, Okumura K, Honda T, Iwasa A, Ashikaga K. Source: Journal of the American College of Cardiology. 2001 April; 37(5): 1415-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300455
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Effects of verapamil and metoprolol on recovery from atrial electrical remodeling after cardioversion of long-lasting atrial fibrillation. Author(s): Bertaglia E, D'Este D, Zerbo F, Michieletto M, Pascotto P. Source: International Journal of Cardiology. 2003 February; 87(2-3): 167-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559536
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Effects of verapamil in normal elderly individuals with left ventricular diastolic dysfunction. Author(s): Hung MJ, Cherng WJ, Wang CH, Kuo LT. Source: Echocardiography (Mount Kisco, N.Y.). 2001 February; 18(2): 123-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11262535
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Efficacy of activated charcoal versus gastric lavage half an hour after ingestion of moclobemide, temazepam, and verapamil. Author(s): Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Source: European Journal of Clinical Pharmacology. 2000 July; 56(4): 285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954340
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Enantioselective transport and CYP3A4-mediated metabolism of R/S-verapamil in Caco-2 cell monolayers. Author(s): Engman H, Tannergren C, Artursson P, Lennernas H. Source: European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences. 2003 May; 19(1): 57-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729862
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Evaluation of the effects of fixed combinations of sustained-release verapamil/trandolapril versus captopril/hydrochlorothiazide on metabolic and electrolyte parameters in patients with essential hypertension. Author(s): Cifkova R, Nakov R, Novozamska E, Hejl Z, Petrzilkova Z, Poledne R, Stavek P, Compagnone D. Source: Journal of Human Hypertension. 2000 June; 14(6): 347-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10878692
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Experience with intraplaque injection of verapamil for Peyronie's disease. Author(s): Levine LA, Goldman KE, Greenfield JM. Source: The Journal of Urology. 2002 August; 168(2): 621-5; Discussion 625-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131321
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Failure of buspirone and verapamil to improve spasmodic torticollis. Author(s): Naber D, Weinberger DR, Gillespie M, Chase TN. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1992 Winter; 4(1): 82-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1627968
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Failure of oral atenolol and verapamil to increase the capacity and duration of exercise in patients in sinus rhythm with mitral stenosis. Author(s): Misra M, Bhandari K, Thakur R, Puri VK. Source: International Journal of Cardiology. 1989 April; 23(1): 37-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2714912
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Failure of preventing 5-fluorouracil cardiotoxicity by prophylactic treatment with verapamil. Author(s): Eskilsson J, Albertsson M. Source: Acta Oncologica (Stockholm, Sweden). 1990; 29(8): 1001-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2278719
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Failure to wean from cardiopulmonary bypass after myocardial revascularization: successful treatment with verapamil via the aortic root. Author(s): Ho AM, Parisi A, Shragge BW. Source: British Journal of Anaesthesia. 1993 October; 71(4): 589-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8260312
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False-positive immunochemical screen for methadone attributable to metabolites of verapamil. Author(s): Lichtenwalner MR, Mencken T, Tully R, Petosa M. Source: Clinical Chemistry. 1998 May; 44(5): 1039-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9590378
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Familial hemiplegic migraine and its abortive therapy with intravenous verapamil. Author(s): Yu W, Horowitz SH. Source: Neurology. 2001 November 13; 57(9): 1732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11706128
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Fasciculations due to verapamil in a patient with neuropathy. Author(s): Thomke F, Vogt T, Roder R, Hopf HC. Source: Journal of Neurology. 1990 November; 237(7): 448-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2177104
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Faster clearance of sustained release verapamil in men versus women: continuing observations on sex-specific differences after oral administration of verapamil. Author(s): Krecic-Shepard ME, Barnas CR, Slimko J, Schwartz JB. Source: Clinical Pharmacology and Therapeutics. 2000 September; 68(3): 286-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11014410
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Fatal verapamil toxicity and hypokalemia. Author(s): Minella RA, Schulman DS. Source: American Heart Journal. 1991 June; 121(6 Pt 1): 1810-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2035398
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Fetal death after successful conversion of fetal supraventricular tachycardia with digoxin and verapamil. Author(s): Owen J, Colvin EV, Davis RO. Source: American Journal of Obstetrics and Gynecology. 1988 May; 158(5): 1169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3369500
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Fexofenadine transport in Caco-2 cells: inhibition with verapamil and ritonavir. Author(s): Perloff MD, von Moltke LL, Greenblatt DJ. Source: Journal of Clinical Pharmacology. 2002 November; 42(11): 1269-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12412827
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Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm. Author(s): Held C, Hjemdahl P, Rehnqvist N, Wallen NH, Bjorkander I, Eriksson SV, Forslund L, Wiman B. Source: Circulation. 1997 May 20; 95(10): 2380-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9170400
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First-pass uptake of verapamil, diazepam, and thiopental in the human lung. Author(s): Roerig DL, Kotrly KJ, Dawson CA, Ahlf SB, Gualtieri JF, Kampine JP. Source: Anesthesia and Analgesia. 1989 October; 69(4): 461-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2782646
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Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. Author(s): Muijsers RB, Curran MP, Perry CM. Source: Drugs. 2002; 62(17): 2539-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12421112
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Fixed combination verapamil SR/trandolapril. Author(s): Dooley M, Goa KL. Source: Drugs. 1998 November; 56(5): 837-44; Discussion 845-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9829157
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Fixed-dose combination therapy with trandolapril and verapamil SR is effective in primary hypertension. Trandolapril Study Group. Author(s): DeQuattro V, Lee D. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1997 July; 10(7 Pt 2): 138S-145S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9231890
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Flow cytometric study of idarubicin and daunorubicin accumulation and the effect of verapamil in leukemic cell lines and fresh cells from patients with acute nonlymphoblastic leukemia. Author(s): Boiron JM, Belloc F, Montastruc M, Cony-Makhoul P, Dumain P, Marit G, Mahon FX, Puntous M, Lopez F, Lacombe F, et al. Source: Leukemia Research. 1994 May; 18(5): 313-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8182921
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Fluorescent verapamil analogue for monitoring acidic intracellular organelles in multidrug resistant and sensitive cells. Author(s): Mankhetkorn S, Teodori E, Garnier-Suillerot A. Source: Chemico-Biological Interactions. 2001 July 31; 137(1): 1-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518560
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Fluorescent verapamil derivative for monitoring activity of the multidrug transporter. Author(s): Lelong IH, Guzikowski AP, Haugland RP, Pastan I, Gottesman MM, Willingham MC. Source: Molecular Pharmacology. 1991 October; 40(4): 490-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1681415
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Forearm vascular alpha 1-adrenergic blockade by verapamil. Author(s): Abernethy DR, Winterbottom LM. Source: Clinical Pharmacology and Therapeutics. 1990 June; 47(6): 755-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2162750
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Gas chromatographic analysis of verapamil and norverapamil in post mortem specimens using a 530-micron fused-silica column with nitrogen-phosphorus detection. Author(s): Chan LT, Chhuy LH, Crowley RJ. Source: Journal of Chromatography. 1987 July 31; 402: 361-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2821043
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Gastric decontamination performed 5 min after the ingestion of temazepam, verapamil and moclobemide: charcoal is superior to lavage. Author(s): Lapatto-Reiniluoto O, Kivisto KT, Neuvonen PJ. Source: British Journal of Clinical Pharmacology. 2000 March; 49(3): 274-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718784
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Gender-specific effects on verapamil pharmacokinetics and pharmacodynamics in humans. Author(s): Krecic-Shepard ME, Barnas CR, Slimko J, Jones MP, Schwartz JB. Source: Journal of Clinical Pharmacology. 2000 March; 40(3): 219-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10709150
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Gut wall metabolism of verapamil in older people: effects of rifampicin-mediated enzyme induction. Author(s): Fromm MF, Dilger K, Busse D, Kroemer HK, Eichelbaum M, Klotz U. Source: British Journal of Clinical Pharmacology. 1998 March; 45(3): 247-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9517368
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Haematoporphyrin derivative--photodynamic therapy of colorectal carcinoma, sensitized using verapamil and adriamycin. Author(s): Purkiss SF, Grahn MF, Williams NS. Source: Surgical Oncology. 1996 August; 5(4): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9067565
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Heart rate-lowering drugs such as verapamil improve aerobic exercise performance in healthy elderly individuals: a new way to look at left ventricular diastolic function in the elderly. Author(s): Bertella M, Valentini P, Valentini R. Source: Journal of the American College of Cardiology. 2000 May; 35(6): 1697-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807480
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Hemodynamic effects of cadralazine or chlorthalidone in verapamil-treated elderly hypertensives. Author(s): Antonicelli R, Savonitto S, Tomassini PF, Gambini C, Sardina M, Paciaroni E. Source: Int J Clin Pharmacol Ther. 1994 April; 32(4): 198-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8032580
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Hemodynamic responses to verapamil monotherapy in patients with renal disease. Author(s): Lenz T, Muller FB, Sotelo JE, Laragh JH, August P. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1991 December; 4(12 Pt 1): 939-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1815650
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Hepatotoxicity due to verapamil hydrochloride. Author(s): de Arriba G, Garcia-Martin F, Sanchez-Heras M, Aldeguer M, Tejero E, Jarillo MD. Source: Eur J Med. 1993 March; 2(3): 179-81. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8261063
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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 variability in drug pharmacokinetics complicates determination of bioequivalence: experience with verapamil. Author(s): Tsang YC, Pop R, Gordon P, Hems J, Spino M. Source: Pharmaceutical Research. 1996 June; 13(6): 846-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792420
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High-dose recombinant interleukin-2/verapamil combination in advanced cancer. Author(s): Tagliaferri P, Correale P, Mottola M, de Simone G, Montesarchio V, Matano E, Rea A, Morabito A, Famiani M, Ciardiello F, Tortora G, Caraglia M, Barile C, Palmieri G, Bianco AR. Source: European Journal of Cancer (Oxford, England : 1990). 1996 July; 32A(8): 1436-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8869114
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High-dose verapamil + trandolapril-induced thrombotic microangiopathy. Author(s): Gokel Y, Paydas S, Acikalin A, Bozkurt A. Source: Haematologia. 2002; 32(3): 281-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611489
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High-dose verapamil-trandolapril induced rhabdomyolysis and acute renal failure. Author(s): Gokel Y, Paydas S, Duru M. Source: The American Journal of Emergency Medicine. 2000 October; 18(6): 738-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11043636
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Human multi-drug-resistant cancer cells exhibit a high degree of selectivity for stereoisomers of verapamil and quinidine. Author(s): Eliason JF, Ramuz H, Kaufmann F. Source: International Journal of Cancer. Journal International Du Cancer. 1990 July 15; 46(1): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2365493
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Hydrochlorothiazide and verapamil in the treatment of hypertension. The Verapamil Versus Diuretic (VERDI) Trial Research Group. Author(s): Holzgreve H, Distler A, Michaelis J, Philipp T, Wellek S. Source: Journal of Cardiovascular Pharmacology. 1991; 18 Suppl 6: S33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1725915
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Hydrochlorothiazide is not additive to verapamil in treating essential hypertension. Author(s): Nicholson JP, Resnick LM, Laragh JH. Source: Archives of Internal Medicine. 1989 January; 149(1): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2643413
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Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men. Author(s): Romeo JH, Dombrowski R, Kwak YS, Fuehrer S, Aron DC. Source: Clinical Endocrinology. 1996 November; 45(5): 571-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8977754
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Hyperthermia and verapamil inhibit the growth of human colon cancer xenografts in vivo through apoptosis. Author(s): Shchepotin IB, McRae DA, Shabahang M, Buras RR, Evans SR. Source: Anticancer Res. 1997 May-June; 17(3C): 2213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9216690
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Hyperthyroid-induced atrial flutter-fibrillation with profound sinoatrial nodal pauses due to small doses of digoxin, verapamil, and propranolol. Author(s): Talley JD, Wathen MS, Hurst JW. Source: Clin Cardiol. 1989 January; 12(1): 45-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2912608
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Hypertrichosis and verapamil. Author(s): Sever PS. Source: Lancet. 1991 November 9; 338(8776): 1215-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1682630
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Hypertrophic cardiomyopathy in pediatric patients: effect of verapamil on regional and global left ventricular diastolic function. Author(s): Pacileo G, De Cristofaro M, Russo MG, Sarubbi B, Pisacane C, Calabro R. Source: The Canadian Journal of Cardiology. 2000 February; 16(2): 146-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10694584
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Hypertrophic cardiomyopathy: long-term effects of propranolol versus verapamil in preventing sudden death in “low-risk” patients. Author(s): Pelliccia F, Cianfrocca C, Romeo F, Reale A. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1990 December; 4(6): 1515-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2081144
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Hypoxia-induced von Willebrand factor release is blocked by verapamil. Author(s): Wilkie ME, Stevens CR, Cunningham J, Blake D. Source: Mineral and Electrolyte Metabolism. 1992; 18(2-5): 141-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1465048
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Idiopathic verapamil-sensitive left ventricular tachycardia complicated by right ventricular outflow tract ventricular tachycardia and ventricular fibrillation. Author(s): Hirao H, Muraoka Y, Yamada T, Hiraoka A, Nakano Y, Sasaki S, Teragawa H, Kato M, Yamagata T, Matsuura H, Kajiyama G. Source: Intern Med. 1999 April; 38(4): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10361910
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In vitro analysis of verapamil-induced immunosuppression: potent inhibition of T cell motility and lymphocytic transmigration through allogeneic endothelial cells. Author(s): Blaheta RA, Hailer NP, Brude N, Wittig B, Leckel K, Oppermann E, Bachmann M, Harder S, Cinatl J, Scholz M, Bereiter-Hahn J, Weber S, Encke A, Markus BH. Source: Transplantation. 2000 February 27; 69(4): 588-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10708116
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In vitro comparison of glyceryl trinitrate-verapamil with other dilators of human saphenous vein. Author(s): Jesuthasan LS, Angus JA, Rosenfeldt FL. Source: Anz Journal of Surgery. 2003 May; 73(5): 313-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752288
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In vitro evaluation of verapamil and other modulating agents in Brazilian chloroquine-resistant Plasmodium falciparum isolates. Author(s): Menezes CM, Kirchgatter K, Di Santi SM, Savalli C, Monteiro FG, Paula GA, Ferreira EI. Source: Revista Da Sociedade Brasileira De Medicina Tropical. 2003 January-February; 36(1): 5-9. Epub 2003 April 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715057
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In vitro performance of floating sustained-release capsule of verapamil. Author(s): Chen GL, Hao WH. Source: Drug Development and Industrial Pharmacy. 1998 November; 24(11): 1067-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876561
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In vivo comparison of putative probes of CYP3A4/5 activity: erythromycin, dextromethorphan, and verapamil. Author(s): Krecic-Shepard ME, Barnas CR, Slimko J, Gorski JC, Wainer IW, Schwartz JB. Source: Clinical Pharmacology and Therapeutics. 1999 July; 66(1): 40-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430108
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Increased dispersion and shortened refractoriness caused by verapamil in chronic atrial fibrillation. Author(s): Ramanna H, Elvan A, Wittkampf FH, de Bakker JM, Hauer RN, Robles de Medina EO. Source: Journal of the American College of Cardiology. 2001 April; 37(5): 1403-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300453
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Increased incidence of infection in verapamil-treated kidney transplant recipients. Author(s): Nanni G, Panocchia N, Tacchino R, Foco M, Piccioni E, Castagneto M. Source: Transplantation Proceedings. 2000 May; 32(3): 551-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10812109
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Increased intracellular concentrations of doxorubicin in resistant lymphoma cells in vivo by concomitant therapy with verapamil and cyclosporin A. Author(s): Tidefelt U, Juliusson G, Elmhorn-Rosenborg A, Peterson C, Paul C. Source: European Journal of Haematology. 1994 May; 52(5): 276-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8020627
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Influence of captopril, propranolol, and verapamil on arterial pulse wave velocity and other cardiovascular parameters in healthy volunteers. Author(s): Kahonen M, Ylitalo R, Koobi T, Turjanmaa V, Ylitalo P. Source: Int J Clin Pharmacol Ther. 1998 September; 36(9): 483-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9760009
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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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Interaction between cyclosporine A and verapamil, felodipine, and isradipine. Author(s): Yildiz A, Sever MS, Turkmen A, Ecder T, Turk S, Akkaya V, Ark E. Source: Nephron. 1999 January; 81(1): 117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9884436
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Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil. Author(s): Cardiovasc Drugs Ther. 2000 Feb;14(1):99-105 Source: Clinical Pharmacology and Therapeutics. 1999 September; 66(3): 239-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755209
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Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience. Author(s): Feng L, Fitzsimmons BF, Young WL, Berman MF, Lin E, Aagaard BD, Duong H, Pile-Spellman J. Source: Ajnr. American Journal of Neuroradiology. 2002 September; 23(8): 1284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12223366
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Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction. Author(s): Werner GS, Lang K, Kuehnert H, Figulla HR. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2002 December; 57(4): 444-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12455077
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Intragraft verapamil: an ounce of prevention is worth a pound of cure. Author(s): Kereiakes DJ, Young JJ, Choo JK, Broderick TM. Source: J Invasive Cardiol. 2002 June; 14(6): 303-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042619
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Intralesional verapamil for the treatment of Peyronie's disease: a review. Author(s): Levine LA, Estrada CR. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2002 October; 14(5): 324-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454681
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Intraplaque verapamil injection for treatment of Peyronie's disease. Author(s): Lasser A, Vandenberg TL, Vincent MJ, Hellstrom WJ. Source: J La State Med Soc. 1998 September; 150(9): 431-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9785755
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Intravenous verapamil blunts hyperdynamic responses during electroconvulsive therapy without altering seizure activity. Author(s): Wajima Z, Yoshikawa T, Ogura A, Imanaga K, Shiga T, Inoue T, Ogawa R. Source: Anesthesia and Analgesia. 2002 August; 95(2): 400-2, Table of Contents. Erratum In: Anesth Analg 2002 October; 95(4): 797. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145060
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Is the fascicle of left bundle branch involved in the reentrant circuit of verapamilsensitive idiopathic left ventricular tachycardia? Author(s): Kuo JY, Tai CT, Chiang CE, Yu WC, Huang JL, Hsieh MH, Hou CJ, Tsai CH, Ding YA, Chen SA. Source: Pacing and Clinical Electrophysiology : Pace. 2003 October; 26(10): 1986-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516339
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Jejunal absorption and metabolism of R/S-verapamil in humans. Author(s): Sandstrom R, Karlsson A, Knutson L, Lennernas H. Source: Pharmaceutical Research. 1998 June; 15(6): 856-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647350
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Lack of effect of verapamil and isosorbide dinitrate on the hepatic clearance of indocyanine green in cirrhosis. Author(s): Merkel C, Bolognesi M, Angeli P, Finucci GF, Amodio P, Bellon S, Gatta A. Source: British Journal of Clinical Pharmacology. 1990 August; 30(2): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2206784
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Lack of effect of verapamil on diurnal and thyrotropin releasing hormone stimulated thyrotropin levels in man. Author(s): Nielsen-Kudsk JE, Bartels PD. Source: Thyroidology. 1990 April; 2(1): 13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1715745
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Lack of inhibition by dideoxy-forskolin and verapamil of DIDS-sensitive volumeactivated Cl- secretion in human squamous lung carcinoma epithelial cells. Author(s): Munkonge FM, Osborne LR, Geddes DM, Alton EW. Source: Biochimica Et Biophysica Acta. 1994 December 30; 1224(3): 342-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7803488
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Lack of interaction of digoxin and P-glycoprotein inhibitors, quinidine and verapamil in human placenta in vitro. Author(s): Holcberg G, Sapir O, Tsadkin M, Huleihel M, Lazer S, Katz M, Mazor M, BenZvi Z. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2003 August 15; 109(2): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860328
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Lack of reversal with verapamil of drug resistance in multiple myeloma. Author(s): Mertens M, Thomas L, vd Lelie J. Source: British Journal of Haematology. 1990 September; 76(1): 155. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2223640
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Left ventricular diastolic filling improvement obtained by intravenous verapamil in mild to moderate essential hypertension: a complex effect. Author(s): Franchi F, Fabbri G, Monopoli A, Rossi D, Matassi L, Strazzulla G, Bisi G. Source: Cardiology. 1989; 76(1): 32-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2706643
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Left ventricular systolic dysfunction precipitated by verapamil in cardiac amyloidosis. Author(s): Pollak A, Falk RH. Source: Chest. 1993 August; 104(2): 618-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8339658
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Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects. Author(s): Sevre K, Lefrandt JD, Eide I, Smit AJ, Rostrup M. Source: Blood Pressure. 2001; 10(2): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467760
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Liquid-chromatographic quantification compared with gas-chromatographic-massspectrometric determination of verapamil and norverapamil in plasma. Author(s): Hynning PA, Anderson P, Bondesson U, Boreus LO. Source: Clinical Chemistry. 1988 December; 34(12): 2502-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3197291
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Lithium ACE inhibitors, NSAIDs, and verapamil. A possible fatal combination. Author(s): Chandragiri SS, Pasol E, Gallagher RM. Source: Psychosomatics. 1998 May-June; 39(3): 281-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9664775
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Liver injury due to verapamil. Author(s): Burgunder JM, Abernethy DR, Lauterburg BH. Source: Hepatogastroenterology. 1988 August; 35(4): 169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3181862
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Long term effects of sustained release verapamil on the renal and systemic haemodynamic parameters in hypertensive patients with mild to severe chronic renal failure. Author(s): Schohn DC, Jahn HA, Maareck M. Source: Drugs. 1993; 46 Suppl 2: 113-9; Discussion 119-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7512464
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Long-acting verapamil and heart failure. Author(s): Mohindra SK, Udeani GO. Source: Jama : the Journal of the American Medical Association. 1989 February 17; 261(7): 994. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2915424
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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 outcome of verapamil-sensitive sustained left ventricular tachycardia in patients without structural heart disease. Author(s): Ohe T, Aihara N, Kamakura S, Kurita T, Shimizu W, Shimomura K. Source: Journal of the American College of Cardiology. 1995 January; 25(1): 54-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7798526
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Long-term prevention of atrial fibrillation after coronary artery bypass surgery: comparison of quinidine, verapamil, and amiodarone in maintaining sinus rhythm. Author(s): Yilmaz AT, Demirkilic U, Arslan M, Kurulay E, Ozal E, Tatar H, Ozturk O. Source: Journal of Cardiac Surgery. 1996 January-February; 11(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8775337
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Long-term treatment of hypertrophic cardiomyopathy with verapamil or propranolol in matched pairs of patients: results of a multicenter study. Author(s): Kober G, Hopf R, Biamino G, Bubenheimer P, Forster K, Kuck KH, Hanrath P, von Olshausen KE, Schlepper M, Kaltenbach M. Source: Zeitschrift Fur Kardiologie. 1987; 76 Suppl 3: 113-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3324526
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Low-dose calcium pretreatment to prevent verapamil-induced hypotension. Author(s): Kuhn M, Schriger DL. Source: American Heart Journal. 1992 July; 124(1): 231-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1615816
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Low-dose verapamil in middle-aged and elderly patients with angina pectoris: no evidence of increased susceptibility to the cardiac effects. Author(s): Ahmed JH, Elliott HL, Meredith PA, Reid JL. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1992 April; 6(2): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1390328
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Lymphocytic intracellular calcium in a patient with complicated verapamil overdose. Author(s): Ori Y, Korzets A, Caneti M, Weinstein T, Chagnac A, Salman H, Malachi T, Gafter U. Source: The American Journal of the Medical Sciences. 2000 January; 319(1): 63-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10653445
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Magnesium oxide augmentation of verapamil maintenance therapy in mania. Author(s): Giannini AJ, Nakoneczie AM, Melemis SM, Ventresco J, Condon M. Source: Psychiatry Research. 2000 February 14; 93(1): 83-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10699232
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Management of esophageal spasm in epidermolysis bullosa dystrophica using verapamil. Author(s): Mitchell JD, Eisenberg M. Source: Journal of Pediatric Gastroenterology and Nutrition. 1989 January; 8(1): 133-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2732859
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Management of massive verapamil overdose. Author(s): Watson NA, FitzGerald CP. Source: The Medical Journal of Australia. 1991 July 15; 155(2): 124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1857291
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Manipulation of cerebrovascular resistance during internal carotid artery occlusion by intraarterial verapamil. Author(s): Joshi S, Young WL, Pile-Spellman J, Duong DH, Hacein-Bey L, Vang MC, Marshall RS, Ostapkovich N, Jackson T. Source: Anesthesia and Analgesia. 1997 October; 85(4): 753-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9322451
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Manipulation of the N-alkyl substituent in amodiaquine to overcome the verapamilsensitive chloroquine resistance component. Author(s): Hawley SR, Bray PG, O'Neill PM, Naisbitt DJ, Park BK, Ward SA. Source: Antimicrobial Agents and Chemotherapy. 1996 October; 40(10): 2345-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8891142
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Massive verapamil overdose complicated by noncardiogenic pulmonary edema. Author(s): Brass BJ, Winchester-Penny S, Lipper BL. Source: The American Journal of Emergency Medicine. 1996 September; 14(5): 459-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8765109
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Mechanism of block and identification of the verapamil binding domain to HERG potassium channels. Author(s): Zhang S, Zhou Z, Gong Q, Makielski JC, January CT. Source: Circulation Research. 1999 May 14; 84(9): 989-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10325236
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Metabolic neutrality of combined verapamil-trandolapril treatment in contrast to beta-blocker-low-dose chlortalidone treatment in hypertensive type 2 diabetes. Author(s): Schneider M, Lerch M, Papiri M, Buechel P, Boehlen L, Shaw S, Risen W, Weidmann P. Source: Journal of Hypertension. 1996 May; 14(5): 669-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8762212
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Methanethiosulfonate derivatives of rhodamine and verapamil activate human Pglycoprotein at different sites. Author(s): Loo TW, Bartlett MC, Clarke DM. Source: The Journal of Biological Chemistry. 2003 December 12; 278(50): 50136-41. Epub 2003 October 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522974
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Mid-diastolic potential is related to the reentrant circuit in a patient with verapamilsensitive idiopathic left ventricular tachycardia. Author(s): Aiba T, Suyama K, Matsuo K, Taguchi A, Shimizu W, Kurita T, Aihara N, Kamakura S. Source: Journal of Cardiovascular Electrophysiology. 1998 September; 9(9): 1004-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9786082
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Mixed-effect modeling for detection and evaluation of drug interactions: digoxinquinidine and digoxin-verapamil combinations. Author(s): Bauer LA, Horn JR, Pettit H. Source: Therapeutic Drug Monitoring. 1996 February; 18(1): 46-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8848820
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Modulation by dietary salt of verapamil disposition in humans. Author(s): Darbar D, Fromm MF, Dell'Orto S, Kim RB, Kroemer HK, Eichelbaum M, Roden DM. Source: Circulation. 1998 December 15; 98(24): 2702-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9851956
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Modulation of mitoxantrone cytotoxicity by verapamil in human chronic myeloid leukemia cells. Author(s): Satyamoorthy K, Chitnis MP, Pradhan SG, Advani SH. Source: Oncology. 1989; 46(2): 128-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2710477
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Modulation of multidrug resistance by three bisbenzyl-isoquinolines in comparison with verapamil. Author(s): Tian H, Pan OC. Source: Zhongguo Yao Li Xue Bao. 1997 September; 18(5): 455-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10322941
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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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Monensin and verapamil do not alter intracellular localisation of daunorubicin in multidrug resistant human KB cells. Author(s): Wood DJ, Rumsby MG, Warr JR. Source: Cancer Letters. 1996 November 12; 108(1): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8950207
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Multidrug resistance circumvention by a new triazinoaminopiperidine derivative S9788 in vitro: definition of the optimal schedule and comparison with verapamil. Author(s): Julia AM, Roche H, Berlion M, Lucas C, Milano G, Robert J, Bizzari JP, Canal P. Source: British Journal of Cancer. 1994 May; 69(5): 868-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8180016
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Multifocal myoclonus due to verapamil overdose. Author(s): Vadlamudi L, Wijdicks EF. Source: Neurology. 2002 March 26; 58(6): 984. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914425
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Myocardial lactate release after intracoronary verapamil application in humans: acute effects of intracoronary verapamil on systemic and coronary hemodynamics, myocardial metabolism, and norepinephrine levels. Author(s): Oldenburg O, Eggebrecht H, Gutersohn A, Schaar J, Brauck K, Haude M, Erbel R, Baumgart D. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001 January; 15(1): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11504164
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Myoclonic seizure following intravenous verapamil injection: case report and review of the literature. Author(s): Maiteh M, Daoud AS. Source: Annals of Tropical Paediatrics. 2001 September; 21(3): 271-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11579867
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Near doubling of heart rate after intravenous verapamil for treatment of atrial fibrillation without preexcitation. Author(s): Orlov YS, Brodsky MA, Orlov MV, Allen B. Source: Pacing and Clinical Electrophysiology : Pace. 1997 November; 20(11): 2867-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9392821
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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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Neurological recovery after prolonged verapamil-induced cardiac arrest. Author(s): Evans JS, Oram MP. Source: Anaesthesia and Intensive Care. 1999 December; 27(6): 653-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631424
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New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene. Author(s): Mickisch GH, Merlino GT, Aiken PM, Gottesman MM, Pastan I. Source: The Journal of Urology. 1991 August; 146(2): 447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1677434
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Nicardipine and verapamil attenuate the pressor response to laryngoscopy and intubation. Author(s): Wig J, Sharma M, Baichoo N, Agarwal A. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1994 December; 41(12): 1185-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7867114
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Nicardipine, verapamil and response to intubation. Author(s): Tobias JD. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1995 July; 42(7): 659-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7554011
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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 and verapamil inhibit the sigmoid colon myoelectric response to eating in healthy volunteers. Author(s): Bassotti G, Calcara C, Annese V, Fiorella S, Roselli P, Morelli A. Source: Diseases of the Colon and Rectum. 1998 March; 41(3): 377-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9514436
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Nifedipine, but not verapamil, acutely elevates parathyroid hormone levels in premenopausal women. Author(s): Wynne AG, Romanski SA, Klee GG, Ory SJ, O'Fallon WM, Fitzpatrick LA. Source: Clinical Endocrinology. 1995 January; 42(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7889637
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No effect of high-protein food on the stereoselective bioavailability and pharmacokinetics of verapamil. Author(s): Hashiguchi M, Ogata H, Maeda A, Hirashima Y, Ishii S, Mori Y, Amamoto T, Handa T, Otsuka N, Irie S, Urae A, Urae R, Kimura R. Source: Journal of Clinical Pharmacology. 1996 November; 36(11): 1022-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8973991
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Noctural dosing of a novel delivery system of verapamil for systemic hypertension. Author(s): White WB. Source: The American Journal of Cardiology. 1996 May 1; 77(11): 1030. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8644635
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Nocturnal dosing of a novel delivery system of verapamil for systemic hypertension. Verapamil Study Group. Author(s): White WB, Anders RJ, MacIntyre JM, Black HR, Sica DA. Source: The American Journal of Cardiology. 1995 August 15; 76(5): 375-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7639163
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Noncardiogenic pulmonary edema complicating massive verapamil overdose. Author(s): Leesar MA, Martyn R, Talley JD, Frumin H. Source: Chest. 1994 February; 105(2): 606-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8306774
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Non-cardiogenic pulmonary oedema in the course of verapamil intoxication. Author(s): Sami Karti S, Ulusoy H, Yandi M, Gunduz A, Kosucu M, Erol K, Ratip S. Source: Emergency Medicine Journal : Emj. 2002 September; 19(5): 458-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12205007
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Non-competitive inhibition of P-glycoprotein-associated efflux of THP-adriamycin by verapamil in living K562 leukemia cells. Author(s): Pereira E, Borrel MN, Fiallo M, Garnier-Suillerot A. Source: Biochimica Et Biophysica Acta. 1994 January 11; 1225(2): 209-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7904185
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Non-invasive haemodynamic study in hypertensive subjects after treatment with verapamil slow release. Author(s): Vulpis V, Seccia TM, Ricci S, Lograno MD, Daniele E, Pirrelli A. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 1994 August-September; 30(2): 153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7816743
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Non-linear pharmacokinetics of high-dose intravenous verapamil. Author(s): Toffoli G, Robieux I, Fantin D, Gigante M, Frustaci S, Nicolosi GL, De Cicco M, Boiocchi M. Source: British Journal of Clinical Pharmacology. 1997 September; 44(3): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9296319
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Nonsteroidal anti-inflammatory drugs after acute myocardial infarction. DAVIT Study Group. Danish Verapamil Infarction Trial. Author(s): Sajadieh A, Wendelboe O, Hansen JF, Mortensen LS. Source: The American Journal of Cardiology. 1999 April 15; 83(8): 1263-5, A9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10215295
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Novel delivery system for verapamil designed to achieve maximal blood pressure control during the early morning. Author(s): Neutel JM, Alderman M, Anders RJ, Weber MA. Source: American Heart Journal. 1996 December; 132(6): 1202-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8969572
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Observations on the effect of verapamil with sodium stibogluconate in kala azar. Author(s): Thakur CP, Kumar M. Source: Trop Geogr Med. 1992 January; 44(1-2): 15-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1323160
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Once-daily fixed dose combinations of verapamil and trandolapril in black patients with mild to moderate hypertension: a new choice for first line treatment. Author(s): Skoularigis J, Strugo V, Radevski I, Hlatswayo Z, Sareli P. Source: Int J Clin Pharmacol Ther. 1997 February; 35(2): 51-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9147707
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Once-daily verapamil in hypertension: intra-arterial recording of blood pressure. Author(s): Brigden GS, Caruana MP, Heber ME, Raftery EB. Source: Br J Clin Pract Suppl. 1988 April; 60: 48-52. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3151271
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Once-daily verapamil in the treatment of mild-to-moderate hypertension: a doubleblind placebo-controlled dose-ranging study. Author(s): Carr AA, Bottini PB, Prisant LM, Fisher LD, Devane JG, O'Brien DE, Rhoades RB. Source: Journal of Clinical Pharmacology. 1991 February; 31(2): 144-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2010560
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Opioid and sympathetic nervous system activity in cluster headache under verapamil or prednisone treatment. Author(s): Figuerola ML, Levin G, Leston J, Barontini M. Source: Headache. 1994 May; 34(5): 257-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8026943
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Oral flecainide, sotalol, and verapamil for the termination of paroxysmal supraventricular tachycardia. Author(s): Hamer AW, Strathmore N, Vohra JK, Hunt VD. Source: Pacing and Clinical Electrophysiology : Pace. 1993 July; 16(7 Pt 1): 1394-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7689205
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Oral propionyl-l-carnitine and intraplaque verapamil in the therapy of advanced and resistant Peyronie's disease. Author(s): Cavallini G, Biagiotti G, Koverech A, Vitali G. Source: Bju International. 2002 June; 89(9): 895-900. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010235
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Oral verapamil and calcium infusion in patients with sick sinus syndrome. Author(s): Midtbo K. Source: Pharmacology & Toxicology. 1987 November; 61(5): 293-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3438222
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Oral verapamil effects on global and regional left ventricular diastolic filling in hypertrophic cardiomyopathy. Author(s): Yamagishi T, Ozaki M, Kusukawa R. Source: Japanese Circulation Journal. 1990 November; 54(11): 1365-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2287041
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Oral verapamil inhibits platelet thrombus formation in humans. Author(s): L-Lacoste L, Lam JY, Hung J, Waters D. Source: Circulation. 1994 February; 89(2): 630-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8313551
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Oral verapamil with chemotherapy for advanced non-small cell lung cancer: a randomised study. Author(s): Millward MJ, Cantwell BM, Munro NC, Robinson A, Corris PA, Harris AL. Source: British Journal of Cancer. 1993 May; 67(5): 1031-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8388231
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Orthotopic liver transplantation and renal function; outcome of hepatorenal syndrome and trial of verapamil for renal protection in nonhepatorenal syndrome. Author(s): Gonwa TA, Goldstein M, Holman M, Husberg BS, Klintmalm GB. Source: Transplantation Proceedings. 1993 April; 25(2): 1891-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8470216
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Overdose of sustained release verapamil. Author(s): Rankin RJ, Edwards IR. Source: N Z Med J. 1990 April 11; 103(887): 165. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2342687
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Overdose of sustained-release verapamil. Author(s): Barrow PM, Houston PL, Wong DT. Source: British Journal of Anaesthesia. 1994 March; 72(3): 361-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8130061
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Patients with persistent atrial fibrillation taking oral verapamil exhibit a lower atrial frequency on the ECG. Author(s): Bollmann A, Sonne K, Esperer HD, Toepffer I, Klein HU. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2002 April; 7(2): 92-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049679
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Pharmacokinetics of controlled-release verapamil in healthy volunteers and patients with hypertension or angina. Author(s): Gupta S, Modi NB, Sathyan G, Ho Pl PL, Aarons L. Source: Biopharmaceutics & Drug Disposition. 2002 January; 23(1): 17-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11891670
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Pharmacokinetics of verapamil and its metabolite norverapamil from a buccal drug formulation. Author(s): Sawicki W, Janicki S. Source: International Journal of Pharmaceutics. 2002 May 15; 238(1-2): 181-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996822
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Pharmacokinetics of verapamil and norverapamil from controlled release floating pellets in humans. Author(s): Sawicki W. Source: European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. 2002 January; 53(1): 29-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11777750
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Plasma atrial natriuretic peptide levels in essential hypertension after treatment with verapamil. Author(s): Kokkas B, Kotridis P, Karamouzis M, Kanonidis I, Sakadamis G, Dadous G, Haritos S, Kyriakoui P, Theodossiadis, Papadopoulos PC, Mirtsou-Fidani V, Papadopoulos CL. Source: Eur J Drug Metab Pharmacokinet. 2002 January-March; 27(1): 45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996326
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Population analyses of sustained-release verapamil in patients: effects of sex, race, and smoking. Author(s): Kang D, Verotta D, Krecic-Shepard ME, Modi NB, Gupta SK, Schwartz JB. Source: Clinical Pharmacology and Therapeutics. 2003 January; 73(1): 31-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12545141
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Postcardioversion atrial electrophysiologic changes induced by oral verapamil in patients with persistent atrial fibrillation. Author(s): Pandozi C, Bianconi L, Calo L, Castro A, Lamberti F, Scianaro MC, Gentilucci G, Santini M. Source: Journal of the American College of Cardiology. 2000 December; 36(7): 2234-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11127466
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Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Author(s): Wang YH, Jones DR, Hall SD. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2004 February; 32(2): 259-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744949
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Pretreatment with intragraft verapamil prior to percutaneous coronary intervention of saphenous vein graft lesions: results of the randomized, controlled vasodilator prevention on no-reflow (VAPOR) trial. Author(s): Michaels AD, Appleby M, Otten MH, Dauterman K, Ports TA, Chou TM, Gibson CM. Source: J Invasive Cardiol. 2002 June; 14(6): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042618
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Preventing increases in early-morning blood pressure, heart rate, and the ratepressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising. Author(s): White WB, Sica DA, Calhoun D, Mansoor GA, Anders RJ. Source: American Heart Journal. 2002 October; 144(4): 657-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360162
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Prevention and treatment of keloids with intralesional verapamil. Author(s): D'Andrea F, Brongo S, Ferraro G, Baroni A. Source: Dermatology (Basel, Switzerland). 2002; 204(1): 60-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834852
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Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. Author(s): Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, Neaton JD, Grimm RH Jr, Hansson L, Lacourciere Y, Muller J, Sleight P, Weber MA, Williams G, Wittes J, Zanchetti A, Anders RJ; CONVINCE Research Group. Source: Jama : the Journal of the American Medical Association. 2003 April 23-30; 289(16): 2073-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709465
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Profound effect of plasma protein binding on the polarized transport of furosemide and verapamil in the Caco-2 model. Author(s): Chung SM, Park EJ, Swanson SM, Wu TC, Chiou WL. Source: Pharmaceutical Research. 2001 April; 18(4): 544-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11451044
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Quantitative assay of verapamil in drugs and serum by capillary isotachophoresis. Author(s): Buzinkaiova T, Skacani I, Netriova J. Source: Pharmazie. 1995 December; 50(12): 799-805. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8584556
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Quantitative determination of verapamil and metabolites in human serum by highperformance liquid chromatography and its application to biopharmaceutic investigations. Author(s): Salama ZB, Dilger C, Czogalla W, Otto R, Jaeger H. Source: Arzneimittel-Forschung. 1989 February; 39(2): 210-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2730689
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Quinine-induced hearing loss in the guinea pig is not affected by the Ca2+ channel antagonist verapamil. Author(s): Jager W, Idrizbegovic E, Karlsson KK, Alvan G. Source: Acta Oto-Laryngologica. 1997 January; 117(1): 46-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039480
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R-(+)-verapamil, S-(-)-verapamil, and racemic verapamil inhibit human retinal pigment epithelial cell contraction. Author(s): Faude F, Enzmann V, Poschmann E, Hoffmann S, Wiedemann P. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2000 June; 238(6): 537-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10943681
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Radionuclide ventriculography: acute and chronic response to verapamil in patients with hypertrophic cardiomyopathy. Author(s): Maul FD, Hopf R, Hor G, Standke R, Richter H, Olbrich HG, Happ J. Source: Zeitschrift Fur Kardiologie. 1987; 76 Suppl 3: 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3433873
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Rate-dependent effect of verapamil on atrial refractoriness. Author(s): Hassan SA, Oral H, Scharf C, Chugh A, Pelosi F, Knight BP, Strickberger SA, Morady F. Source: Journal of the American College of Cardiology. 2003 February 5; 41(3): 446-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12575974
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Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial. Author(s): Black HR, Elliott WJ, Neaton JD, Grandits G, Grambsch P, Grimm RH Jr, Hansson L, Lacouciere Y, Muller J, Sleight P, Weber MA, White WB, Williams G, Wittes J, Zanchetti A, Fakouhi TD. Source: Controlled Clinical Trials. 1998 August; 19(4): 370-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9683312
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Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension. Author(s): Pepine CJ, Handberg-Thurmond E, Marks RG, Conlon M, Cooper-DeHoff R, Volkers P, Zellig P. Source: Journal of the American College of Cardiology. 1998 November; 32(5): 1228-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9809930
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R-dl-verapamil downmodulates multidrug resistance of KBv200 cells to vincristine and doxorubicin. Author(s): Fang G, Yang YL, Li JS, Zhang ZX. Source: Zhongguo Yao Li Xue Bao. 1999 July; 20(7): 647-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10678132
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Refractory no-reflow successfully treated with local infusion of high-dose adenosine and verapamil--a case report. Author(s): Dillon WC, Hadian D, Ritchie ME. Source: Angiology. 2001 February; 52(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228087
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Regression of left ventricular hypertrophy in hypertensive heart transplant recipients treated with enalapril, furosemide, and verapamil. Author(s): Angermann CE, Spes CH, Willems S, Dominiak P, Kemkes BM, Theisen K. Source: Circulation. 1991 August; 84(2): 583-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1830519
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Resolution of ST-segment elevation following intravenous administration of nitroglycerin and verapamil. Author(s): Beltrame JF, Stewart S, Leslie S, Poropat S, Horowitz JD. Source: The American Journal of Cardiology. 2002 February 15; 89(4): 452-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11835928
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Reversal of adriamycin resistance in ovarian carcinoma cell line by combination of verapamil and low-level ultrasound. Author(s): Yu T, Hu K, Bai J, Wang Z. Source: Ultrasonics Sonochemistry. 2003 January; 10(1): 37-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457949
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Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease. Author(s): White WB, Johnson MF, Anders RJ, Elliott WJ, Black HR. Source: American Heart Journal. 2001 December; 142(6): 1010-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717605
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Short-term histopathologic effects of different intracavernosal agents on corpus cavernosum and antifibrotic activity of intracavernosal verapamil: an experimental study. Author(s): Sahin M, Basar MM, Bozdogan O, Atan A. Source: Urology. 2001 September; 58(3): 487-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549511
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Significance of late diastolic potential preceding Purkinje potential in verapamilsensitive idiopathic left ventricular tachycardia. Author(s): Tsuchiya T, Okumura K, Honda T, Honda T, Iwasa A, Yasue H, Tabuchi T. Source: Circulation. 1999 May 11; 99(18): 2408-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10318662
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Slow ventricular tachycardia located in the epicardium of the left ventricular base and characterized by effects of adenosine triphosphate, nicorandil and verapamil. Author(s): Kobayashi Y, Miyata A, Tanno K, Kikushima S, Baba T, Katagiri T. Source: Japanese Circulation Journal. 1998 December; 62(12): 947-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890211
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Strategies to antagonise the cyclosporine A-induced proliferation of human pulmonary artery smooth muscle cells: anti-endothelin-1 antibodies, verapamil, and octreotide. Author(s): Medina J, Wolf A. Source: Biochemical Pharmacology. 2000 June 1; 59(11): 1459-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10751556
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Structure-activity studies of verapamil analogs that modulate transport of leukotriene C(4) and reduced glutathione by multidrug resistance protein MRP1. Author(s): Loe DW, Oleschuk CJ, Deeley RG, Cole SP. Source: Biochemical and Biophysical Research Communications. 2000 September 7; 275(3): 795-803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10973801
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Successful resuscitation of a verapamil-intoxicated patient with percutaneous cardiopulmonary bypass. Author(s): Holzer M, Sterz F, Schoerkhuber W, Behringer W, Domanovits H, Weinmar D, Weinstabl C, Stimpfl T. Source: Critical Care Medicine. 1999 December; 27(12): 2818-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628632
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Symptomatic bradycardia secondary to interaction between topical timolol maleate, verapamil, and flecainide: a case report. Author(s): Minish T, Herd A. Source: The Journal of Emergency Medicine. 2002 April; 22(3): 247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932086
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Synergistic effects of verapamil and anti-mdr1 ribozyme on reversion of multidrug resistance in the P-glycoprotein-positive K562 cell line. Author(s): Gong Y, Han W, Liu J, Chen F, Han J, Jin Y, Yong RO. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 April; 15(4): 696-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11368386
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Synthesis and binding properties of photoactivable biotin-conjugated verapamil derivatives for the study of P-170 glycoprotein. Author(s): Teodori E, Ettori D, Garnier-Suillerot A, Gualtieri F, Manetti D, Romanelli MN, Scapecchi S. Source: Bioorganic & Medicinal Chemistry. 1999 September; 7(9): 1873-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10530935
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The effect of verapamil on response of coronary vasomotion to handgrip exercise in symptomatic patients with hypertrophic cardiomyopathy. Author(s): Dimitrow PP, Krzanowski M, Nitankowski R, Szczeklik A, Dubiel JS. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001 July; 15(4): 331-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11800417
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The fluorescent probe Bodipy-FL-verapamil is a substrate for both P-glycoprotein and multidrug resistance-related protein (MRP)-1. Author(s): Crivellato E, Candussio L, Rosati AM, Bartoli-Klugmann F, Mallardi F, Decorti G. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2002 May; 50(5): 731-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967284
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The verapamil versus amlodipine in nondiabetic nephropathies treated with trandolapril (VVANNTT) study. Author(s): Boero R, Rollino C, Massara C, Berto IM, Perosa P, Vagelli G, Lanfranco G, Quarello F. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 July; 42(1): 67-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12830458
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Transdermal application of verapamil gel to the penile shaft fails to infiltrate the tunica albuginea. Author(s): Martin DJ, Badwan K, Parker M, Mulhall JP. Source: The Journal of Urology. 2002 December; 168(6): 2483-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441945
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Transdermal electromotive administration of verapamil and dexamethasone for Peyronie's disease. Author(s): Di Stasi SM, Giannantoni A, Capelli G, Jannini EA, Virgili G, Storti L, Vespasiani G. Source: Bju International. 2003 June; 91(9): 825-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780842
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Transient kinetic and dynamic interactions between verapamil and dofetilide, a class III antiarrhythmic. Author(s): Johnson BF, Cheng SL, Venitz J. Source: Journal of Clinical Pharmacology. 2001 November; 41(11): 1248-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11697758
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Treatment of no-reflow phenomenon with verapamil after primary stent deployment during myocardial infarction. Author(s): Demir I, Yilmaz H, Ermis C, Sancaktar O. Source: Japanese Heart Journal. 2002 November; 43(6): 573-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558122
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Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil. Author(s): Lastimosa AC. Source: Neurology. 2003 September 9; 61(5): 721-2; Author Reply 722. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963781
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Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil. Author(s): Yu W, Horowitz SH. Source: Neurology. 2003 January 14; 60(1): 120-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525732
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Two cases of polymorphic ventricular tachycardia induced by the administration of verapamil against paroxysmal supraventricular tachycardia. Author(s): Shiraishi H, Ishibashi K, Urao N, Hyogo M, Tsukamoto M, Keira N, Hirasaki S, Seo Y, Shirayama T, Nakagawa M. Source: Intern Med. 2002 June; 41(6): 445-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135176
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Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans. Author(s): Schwarz UI, Gramatte T, Krappweis J, Berndt A, Oertel R, von Richter O, Kirch W. Source: Clinical Pharmacology and Therapeutics. 1999 March; 65(3): 283-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10096260
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Update of effects of calcium antagonists in myocardial infarction or angina in light of the second Danish Verapamil Infarction Trial (DAVIT-II) and other recent studies. Author(s): Yusuf S, Held P, Furberg C. Source: The American Journal of Cardiology. 1991 June 1; 67(15): 1295-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2035457
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Use of an in vitro absorption model system for predicting sustained release of verapamil. Author(s): Neubert R, Fahr F, Mader C, Lucke L, Fries G, Rostock G. Source: Arzneimittel-Forschung. 1992 September; 42(9): 1098-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1445475
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Use of cell culture for optimisation of direct antiatherogenic therapy with verapamil. Author(s): Orekhov AN, Pivovarova EM, Sobenin IA, Yakushkin VV, Tertov VV. Source: Drugs. 1992; 44 Suppl 1: 105-110. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1283571
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Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term single-blind study. Author(s): Rehman J, Benet A, Melman A. Source: Urology. 1998 April; 51(4): 620-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9586617
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Use of partial liquid ventilation to manage pulmonary complications of acute verapamil-sustained release poisoning. Author(s): Szekely LA, Thompson BT, Woolf A. Source: Journal of Toxicology. Clinical Toxicology. 1999; 37(4): 475-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10465244
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Use of verapamil and nitroglycerin solution in preparation of radial artery for coronary grafting. Author(s): He GW, Yang CQ. Source: The Annals of Thoracic Surgery. 1996 February; 61(2): 610-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8572775
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Use of verapamil for the symptomatic treatment of microscopic colitis. Author(s): Scheidler MD, Meiselman M. Source: Journal of Clinical Gastroenterology. 2001 April; 32(4): 351-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11276283
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Use of verapamil in the treatment of diarrhea due to microscopic colitis. Author(s): Floch MH. Source: Journal of Clinical Gastroenterology. 2001 April; 32(4): 283. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11276270
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Usefulness of combined propranolol and verapamil for evaluation of surgical ablation of accessory atrioventricular connections in patients without structural heart disease. Author(s): Milstein S, Dunnigan A, Buetikofer J, Benditt DG, Crosson J, Pineda E. Source: The American Journal of Cardiology. 1990 November 15; 66(17): 1216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2239726
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Verapamil (VP) improves the outcome after renal transplantation (CRT). Author(s): Dawidson I, Lu C, Palmer B, Peters P, Rooth P, Risser R, Sagalowsky A, Sandor Z. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 1992; 5 Suppl 1: S60-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14621733
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Verapamil inhibits interleukin-6 and vascular endothelial growth factor production in primary cultures of keloid fibroblasts. Author(s): Giugliano G, Pasquali D, Notaro A, Brongo S, Nicoletti G, D'Andrea F, Bellastella A, Sinisi AA. Source: British Journal of Plastic Surgery. 2003 December; 56(8): 804-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615256
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VErapamil plus antiarrhythmic drugs reduce atrial fibrillation recurrences after an electrical cardioversion (VEPARAF Study). Author(s): De Simone A, De Pasquale M, De Matteis C, Canciello M, Manzo M, Sabino L, Alfano F, Di Mauro M, Campana A, De Fabrizio G, Vitale DF, Turco P, Stabile G. Source: European Heart Journal. 2003 August; 24(15): 1425-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909071
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Verapamil reverts acute renal functional impairment induced by angiotensin II converting enzyme inhibitors. Author(s): Macias-Nunez JF, Fernandez R, Calvo C, Grande J, Herrera J, Bustamante J, Garay R, Robles R, Lopez-Novoa JM. Source: Renal Failure. 2003 September; 25(5): 727-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575281
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Verapamil sensitive idiopathic ventricular tachycardia in an infant. Author(s): Wang JD, Fu YC, Jan SL, Chi CS. Source: Japanese Heart Journal. 2003 September; 44(5): 667-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587648
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Verapamil, atrial fibrillation recurrences and anticoagulation. Author(s): Auer J, Weber T, Berent R, Eber B. Source: European Heart Journal. 2004 January; 25(2): 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720538
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Verapamil: identification of novel metabolites in cultures of primary human hepatocytes and human urine by LC-MS(n) and LC-NMR. Author(s): Borlak J, Walles M, Elend M, Thum T, Preiss A, Levsen K. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2003 June; 33(6): 655-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851041
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Verapamil: metabolism in cultures of primary human coronary arterial endothelial cells. Author(s): Borlak J, Walles M, Levsen K, Thum T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 July; 31(7): 888-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814965
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Verapamil-induced electrical and cycle length alternans during supraventricular tachycardia: what is the mechanism? Author(s): Luzza F, Oreto G. Source: Journal of Cardiovascular Electrophysiology. 2003 March; 14(3): 323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716120
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Verapamil-sensitive idiopathic left ventricular tachycardia in pregnancy. Author(s): Cleary-Goldman J, Salva CR, Infeld JI, Robinson JN. Source: J Matern Fetal Neonatal Med. 2003 August;14(2):132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629096
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CHAPTER 2. NUTRITION AND VERAPAMIL Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and verapamil.
Finding Nutrition Studies on Verapamil 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 “verapamil” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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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 “verapamil” (or a synonym): •
A comparison of the modulation of antiblastics cytotoxicity by verapamil and dipyridamole in a human colon carcinoma cell line. Author(s): Department of Pharmacology Egidio Meneghetti, University of Padova, 35131 Padova, Italy. Source: Berti, E Carrara, M Ragazzi, E D'Ancona, S Berti, T Int-J-Oncol. 1999 July; 15(1): 155-60 1019-6439
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Chiral recognition of verapamil by cyclodextrins studied with capillary electrophoresis, NMR spectroscopy, and electrospray ionization mass spectrometry. Author(s): Institute of Pharmaceutical Chemistry, University of Munster, Hittorfstrasse 58-62, 48149 Munster, Germany. Source: Chankvetadze, B Burjanadze, N Pintore, G Strickmann, D Bergenthal, D Blaschke, G Chirality. 1999; 11(8): 635-44 0899-0042
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Different effects of verapamil and low calcium on repetitive contractile activity of frog fatigue-resistant and easily-fatigued muscle fibres. Author(s): Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlarska, Bratislava. Source: Lipska, E Radzyukevich, T Gen-Physiol-Biophys. 1999 June; 18(2): 139-53 02315882
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Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Author(s): Institute for Pharmacology, Clinical Pharmacology, University of Koln, Germany.
[email protected] Source: Fuhr, U Muller Peltzer, H Kern, R Lopez Rojas, P Junemann, M Harder, S Staib, A H Eur-J-Clin-Pharmacol. 2002 April; 58(1): 45-53 0031-6970
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Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal. Author(s): Institute of Physiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
[email protected] Source: Lazarova, M Petkova, B Staneva Stoycheva, D Methods-Find-Exp-ClinPharmacol. 1999 December; 21(10): 669-71 0379-0355
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Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds (Meriones unguiculatus). Author(s): Institute of Parasitology, McGill University, Sainte Anne-de-Bellevue, Quebec, Canada. Source: Molento, M B Prichard, R K Parasitol-Res. 1999 December; 85(12): 1007-11 09320113
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Enhanced absorption of pour-on ivermectin formulation in rats by co-administration of the multidrug-resistant-reversing agent verapamil. Author(s): Laboratoire de Pharmacologie-Toxicologie, INRA, Toulouse, France.
[email protected] Source: Alvinerie, M Dupuy, J Eeckhoutte, C Sutra, J F Parasitol-Res. 1999 November; 85(11): 920-2 0932-0113
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Oral propionyl-l-carnitine and intraplaque verapamil in the therapy of advanced and resistant Peyronie's disease. Author(s): Medicine Reproductive Unit, Societa Italiana Studi di Medicina della Riproduzione (SISMER), Bologna, Italy.
[email protected]
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Source: Cavallini, G Biagiotti, G Koverech, A Vitali, G BJU-Int. 2002 June; 89(9): 895-900 1464-4096 •
Slow ventricular tachycardia located in the epicardium of the left ventricular base and characterized by effects of adenosine triphosphate, nicorandil and verapamil. Author(s): Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. Source: Kobayashi, Y Miyata, A Tanno, K Kikushima, S Baba, T Katagiri, T Jpn-Circ-J. 1998 December; 62(12): 947-51 0047-1828
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Synthesis and binding properties of photoactivable biotin-conjugated verapamil derivatives for the study of P-170 glycoprotein. Author(s): Dipartimento di Scienze Farmaceutiche, Universita' di Firenze, Italy. Source: Teodori, E Ettori, D Garnier Suillerot, A Gualtieri, F Manetti, D Romanelli, M N Scapecchi, S Bioorg-Med-Chem. 1999 September; 7(9): 1873-80 0968-0896
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The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil. Author(s): Department of Medicine A, Assaf Harofeh Medical Center, Zerifin, Israel. Source: Zaidenstein, R Dishi, V Gips, M Soback, S Cohen, N Weissgarten, J Blatt, A Golik, A Eur-J-Clin-Pharmacol. 1998 June; 54(4): 337-40 0031-6970
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The effects of anticancer drugs in combination with nimodipine and verapamil on cultured cells of glioblastoma multiforme. Author(s): Department of Neurosurgery, Medical Faculty, Osmangazi University, Eskisehir, Turkey.
[email protected] Source: Durmaz, R Deliorman, S Uyar, R Isiksoy, S Erol, K Tel, E Clin-NeurolNeurosurg. 1999 December; 101(4): 238-44 0303-8467
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Use of intralesional verapamil to dissolve Peyronie's disease plaque: a long-term single-blind study. Author(s): Department of Urology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York 10467, USA. Source: Rehman, J Benet, A Melman, A Urology. 1998 April; 51(4): 620-6 0090-4295
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Verapamil- and cadmium-resistant stimulation of calcium uptake and insulin release by D-glucose in depolarised pancreatic islets exposed to diazoxide. Author(s): Laboratory of Experimental Medicine, Brussels Free University, Belgium. Source: Jijakli, H Malaisse, W J Cell-Signal. 1998 October; 10(9): 661-5 0898-6568
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/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to Verapamil; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Alternative names: Calciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com
Nutrition
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Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Channel–Blockers Source: Prima Communications, Inc.www.personalhealthzone.com Calcium-Channel Blockers Source: Healthnotes, Inc.; www.healthnotes.com D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND VERAPAMIL Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to verapamil. 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 verapamil 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 “verapamil” (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 verapamil: •
A comparison of the modulation of antiblastics cytotoxicity by verapamil and dipyridamole in a human colon carcinoma cell line. Author(s): Berti E, Carrara M, Ragazzi E, D'Ancona S, Berti T. Source: International Journal of Oncology. 1999 July; 15(1): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10375609
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A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning. Author(s): Smith DH, Neutel JM, Weber MA. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 January; 14(1): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11206672
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A steady-state evaluation of the bioavailability of chronotherapeutic oral drug absorption system verapamil PM after nighttime dosing versus immediate-acting
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verapamil dosed every eight hours. Author(s): Prisant LM, Devane JG, Butler J. Source: American Journal of Therapeutics. 2000 November; 7(6): 345-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11304641 •
Adaptive response towards adriamycin in vitro: circumvention with verapamil. Author(s): Anuszewska EL, Koziorowska JH. Source: Mutation Research. 1999 December 16; 431(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10656483
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Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites. Author(s): Neuhoff S, Langguth P, Dressler C, Andersson TB, Regardh CG, SpahnLangguth H. Source: Int J Clin Pharmacol Ther. 2000 April; 38(4): 168-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10783826
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Alpha-tocopherol antagonizes the multidrug-resistance-reversal activity of cyclosporin A, verapamil, GF120918, clofazimine and B669. Author(s): Van Rensburg CE, Joone G, Anderson R. Source: Cancer Letters. 1998 May 15; 127(1-2): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9619865
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Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay. Author(s): Doppenschmitt S, Langguth P, Regardh CG, Andersson TB, Hilgendorf C, Spahn-Langguth H. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 January; 288(1): 348-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862789
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Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. Author(s): Germann UA, Ford PJ, Shlyakhter D, Mason VS, Harding MW. Source: Anti-Cancer Drugs. 1997 February; 8(2): 141-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9073310
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Chronotherapeutic delivery of verapamil in obese versus non-obese patients with essential hypertension. Author(s): White WB, Elliott WJ, Johnson MF, Black HR.
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Source: Journal of Human Hypertension. 2001 February; 15(2): 135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317194 •
Circadian variations and chronotherapeutic implications for cardiovascular management: a focus on COER verapamil. Author(s): Glasser SP. Source: Heart Disease. 1999 September-October; 1(4): 226-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720629
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Combination chemotherapy with cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD) plus oral quinine and verapamil in patients with advanced breast cancer. Author(s): Taylor CW, Dalton WS, Mosley K, Dorr RT, Salmon SE. Source: Breast Cancer Research and Treatment. 1997 January; 42(1): 7-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9116320
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Comparative effect of verapamil, cyclosporin A and SDZ PSC 833 on rhodamine 123 transport and cell cycle in vinblastine-resistant Chinese hamster ovary cells overexpressing P-glycoprotein. Author(s): Petriz J, Sanchez J, Bertran J, Garcia-Lopez J. Source: Anti-Cancer Drugs. 1997 October; 8(9): 869-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9402314
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Comparison of effects of controlled onset extended release verapamil at bedtime and nifedipine gastrointestinal therapeutic system on arising on early morning blood pressure, heart rate, and the heart rate-blood pressure product. Author(s): White WB, Black HR, Weber MA, Elliott WJ, Bryzinski B, Fakouhi TD. Source: The American Journal of Cardiology. 1998 February 15; 81(4): 424-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9485131
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Direct interaction between verapamil and doxorubicin causes the lack of reversal effect of verapamil on P-glycoprotein mediated resistance to doxorubicin in vitro using L1210/VCR cells. Author(s): Breier A, Drobna Z, Barancik M. Source: Neoplasma. 1998; 45(4): 248-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9890669
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Drug accumulation in the presence of the multidrug resistance pump: dissociation between verapamil accumulation and the action of P-glycoprotein. Author(s): Ayesh S, Litman T, Stein WD. Source: Receptors & Channels. 1997; 5(3-4): 175-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9606721
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Effect of high dose verapamil on restenosis after peripheral angioplasty. Author(s): Schweizer J, Kirch W, Koch R, Hellner G, Uhlmann K. Source: Journal of the American College of Cardiology. 1998 May; 31(6): 1299-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9581724
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Effects of carvedilol on MDR1-mediated multidrug resistance: comparison with verapamil. Author(s): Kakumoto M, Sakaeda T, Takara K, Nakamura T, Kita T, Yagami T, Kobayashi H, Okamura N, Okumura K. Source: Cancer Science. 2003 January; 94(1): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12708479
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Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Author(s): Fuhr U, Muller-Peltzer H, Kern R, Lopez-Rojas P, Junemann M, Harder S, Staib AH. Source: European Journal of Clinical Pharmacology. 2002 April; 58(1): 45-53. Epub 2002 March 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956673
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Effects of the chronotherapeutic delivery of verapamil on circadian blood pressure in African-American patients with hypertension. Author(s): White WB, Johnson MF, Black HR, Fakouhi TD. Source: Ethn Dis. 1999 Autumn; 9(3): 341-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10600056
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Evidence for a constitutive, verapamil-sensitive, non-P-glycoprotein multidrug resistance phenotype in malignant glioma that is unaltered by radiochemotherapy in vivo. Author(s): Rieger L, Rieger J, Winter S, Streffer J, Esser P, Dichgans J, Meyermann R, Weller M. Source: Acta Neuropathologica. 2000 May; 99(5): 555-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10805101
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High-dose verapamil + trandolapril-induced thrombotic microangiopathy. Author(s): Gokel Y, Paydas S, Acikalin A, Bozkurt A. Source: Haematologia. 2002; 32(3): 281-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611489
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High-dose verapamil-trandolapril induced rhabdomyolysis and acute renal failure. Author(s): Gokel Y, Paydas S, Duru M. Source: The American Journal of Emergency Medicine. 2000 October; 18(6): 738-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11043636
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Mechanism of electrical stimulation-induced neuroprotection: effects of verapamil on protection of primary auditory afferents. Author(s): Miller AL, Prieskorn DM, Altschuler RA, Miller JM. Source: Brain Research. 2003 March 21; 966(2): 218-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618345
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Modulation of multidrug resistance by three bisbenzyl-isoquinolines in comparison with verapamil. Author(s): Tian H, Pan OC. Source: Zhongguo Yao Li Xue Bao. 1997 September; 18(5): 455-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10322941
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Modulation of vincristine cytotoxicity by dexverapamil in sensitive and resistant HL60 cell lines as a function of extracellular protein binding. Author(s): Stratmann G, Harder S, Holzer D, Hofmann WK, Ottmann OG, Woodcock BG, Hoffmann WK. Source: Int J Clin Pharmacol Ther. 1998 February; 36(2): 103-6. No Abstract Available. Erratum In: Int J Clin Pharmacol Ther 2000 January; 38(1): 46. Hoffmann Wk[corrected to Hofmann Wk]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9520158
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Neurological recovery after prolonged verapamil-induced cardiac arrest. Author(s): Evans JS, Oram MP. Source: Anaesthesia and Intensive Care. 1999 December; 27(6): 653-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631424
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Neuron degeneration induced by verapamil and attenuated by EGb761. Author(s): Zhu L, Gao J, Wang Y, Zhao XN, Zhang ZX. Source: J Basic Clin Physiol Pharmacol. 1997; 8(4): 301-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9651802
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Non-linear pharmacokinetics of high-dose intravenous verapamil. Author(s): Toffoli G, Robieux I, Fantin D, Gigante M, Frustaci S, Nicolosi GL, De Cicco M, Boiocchi M. Source: British Journal of Clinical Pharmacology. 1997 September; 44(3): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9296319
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Pharmacokinetic and pharmacodynamic effects of high-dose continuous intravenous verapamil infusion: clinical experience in the intensive care unit. Author(s): De Cicco M, Macor F, Robieux I, Zanette G, Fantin D, Fabiani F, Nicolosi G, Fracasso A, Toffoli G, Santantonio C, Lestuzzi C, Matovic M, Boiocchi M.
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Source: Critical Care Medicine. 1999 February; 27(2): 332-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075058 •
Portal hypotensive effects of tetrandrine and verapamil in portal hypertensive rats. Author(s): Liu TB, Lin HC, Huang YT, Sun CM, Hong CY. Source: The Journal of Pharmacy and Pharmacology. 1997 January; 49(1): 85-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9120776
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Protection against liver ischemia-reperfusion injury in rats by silymarin or verapamil. Author(s): Oliveira CP, Lopasso FP, Laurindo FR, Leitao RM, Laudanna AA. Source: Transplantation Proceedings. 2001 September; 33(6): 3010-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11543828
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R-dl-verapamil downmodulates multidrug resistance of KBv200 cells to vincristine and doxorubicin. Author(s): Fang G, Yang YL, Li JS, Zhang ZX. Source: Zhongguo Yao Li Xue Bao. 1999 July; 20(7): 647-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10678132
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Simultaneous determination of cytotoxic (adriamycin, vincristine) and modulator of resistance (verapamil, S 9788) drugs in human cells by high-performance liquid chromatography and ultraviolet detection. Author(s): Tassin JP, Dubois J, Atassi G, Hanocq M. Source: J Chromatogr B Biomed Sci Appl. 1997 April 11; 691(2): 449-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9174283
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The effects of anticancer drugs in combination with nimodipine and verapamil on cultured cells of glioblastoma multiforme. Author(s): Durmaz R, Deliorman S, Uyar R, Isiksoy S, Erol K, Tel E. Source: Clinical Neurology and Neurosurgery. 1999 December; 101(4): 238-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622452
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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 modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia. Author(s): den Boer ML, Pieters R, Kazemier KM, Janka-Schaub GE, Henze G, Veerman AJ.
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Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 June; 12(6): 912-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9639420 •
Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Author(s): Belpomme D, Gauthier S, Pujade-Lauraine E, Facchini T, Goudier MJ, Krakowski I, Netter-Pinon G, Frenay M, Gousset C, Marie FN, Benmiloud M, Sturtz F. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2000 November; 11(11): 1471-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11142488
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Verapamil inhibits tumor protease production, local invasion and metastasis development in murine carcinoma cells. Author(s): Farias EF, Aguirre Ghiso JA, Ladeda V, Bal de Kier Joffe E. Source: International Journal of Cancer. Journal International Du Cancer. 1998 December 9; 78(6): 727-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9833766
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Verapamil metabolites: potential P-glycoprotein-mediated multidrug resistance reversal agents. Author(s): Woodland C, Koren G, Wainer IW, Batist G, Ito S. Source: Canadian Journal of Physiology and Pharmacology. 2003 August; 81(8): 800-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897809
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Verapamil sensitisation to alkaloids on colchicine-selected human colon adenocarcinoma cells. Author(s): Ruiz Gomez MJ, Souviron A, Gil L, Martinez Morillo M. Source: J Physiol Biochem. 2001 December; 57(4): 343-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005037
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Verapamil-stimulated glutathione transport by the multidrug resistance-associated protein (MRP1) in leukaemia cells. Author(s): Cullen KV, Davey RA, Davey MW. Source: Biochemical Pharmacology.
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to Verapamil; 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 High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Borago Alternative names: Borage; Borago officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Calciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com
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Calcitrol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Cholecalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Erocalciferol Alternative names: Vitamin D Source: Integrative Medicine Communications; www.drkoop.com Fiber Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ribes Alternative names: Black Currant; Ribes nigrum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Verapamil Source: Healthnotes, Inc.; www.healthnotes.com Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON VERAPAMIL Overview In this chapter, we will give you a bibliography on recent dissertations relating to verapamil. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “verapamil” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on verapamil, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Verapamil ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to verapamil. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Stereoselective metabolism of verapamil and four other chiral drugs by cDNA expressed CYP450's by Shen, Lixin; PhD from University of Illinois at Chicago, Health Sciences Center, 2003, 394 pages http://wwwlib.umi.com/dissertations/fullcit/3083957
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON VERAPAMIL 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 “verapamil” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on verapamil, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Verapamil By performing a patent search focusing on verapamil, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on verapamil: •
Active compounds for use in the treatment of tumors Inventor(s): Eichelbaum; Michel (Ludwigsburg, DE), Kretzschmar; Rolf (Gruenstadt, DE), Schlick; Erich (Neuhofen, DE) Assignee(s): Basf Aktiengesellschaft (ludwigshafen, De) Patent Number: 5,057,304 Date filed: January 3, 1989 Abstract: Antitumor compositions and methods in which a cancerostatic agent and an effective amount of (+)-verapamil, (+)-gallopamil, (+)-devapamil and/or (+)-emopamil which reinforce the antitumor action of the cancerostatic agent are administered to a patient either together or in sequence. Excerpt(s): German Patent 1,154,810 describes phenylacetonitriles which are substituted by basic groups. From this class of compounds, verapamil and gallopamil have proven useful in the therapy of coronary heart disease and of high blood pressure, owing to their calciumantagonistic action. Both compounds are used in the racemic form in therapy. German Laid-Open Application DOS 2,059,923 describes levorotatory antipodes of verapamil and gallopamil. Both compounds are substantially superior to the racemate in coronary activity. German Patent 2,059,985 discloses dextrorotatory antipodes of verapamil and gallopamil. Both dextrorotatory compounds are inferior to the racemate in coronary activity. European Laid-Open Application 147,707 describes antipodes of emopamil and their use for the protective treatment of hypoxic tissue damage. Both enantiomers have a dose-dependent protective action. The effective dose of the levorotatory antipodes is lower than that of the dextrorotatory antipodes by a factor of from 8 to 10. The substantial superiority of the levorotatory antipodes of verapamil, gallopamil and devapamil with regard to their cardiac effect is also described by H. Nawrath and M. Raschack (Cell. Calcium 5 (1984), 316). The calciumantagonistic action of the levorotatory antipodes is superior to that of the dextrorotatory antipodes by a factor of 200. In the negative inotropic action, the difference was found to correspond to a factor of up to 90. Web site: http://www.delphion.com/details?pn=US05057304__
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Alginate-based verapamil-containing depot drug form Inventor(s): Balz; Evamarie (Weinheim, DE), Dresen; Peter (Viernheim, DE), Einig; Heinz (Neustadt, DE) Assignee(s): Knoll AG (ludwigshafen, De) Patent Number: 5,132,295 Date filed: January 24, 1991 Abstract: An alginate-based depot drug form for which the rate of release of the active substance in vitro can be adjusted very precisely is described. Excerpt(s): The present invention relates to the preparation of a verapamil-containing alginate-based depot drug form. It has already been disclosed that alginates can be used for preparing depot drugs (Pharm. Ind., 33, 296 (1971) and Arzneim. Forsch. (Drug Res.)
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25, 1272 (1975)). The alginate contained in the drug form swells in the gastric or intestinal fluid to form a gel matrix which envelopes the active substance. The active substance is released from the drug form over a period of about 6 to 10 hours by diffusion and breakdown of the gel matrix. To date, it has been possible to influence the release of active substance in alginate-based depot forms only by considerable alterations in the amount of alginate used, by alteration of the preparation process and by changing the amount and nature of the other auxiliaries used. Web site: http://www.delphion.com/details?pn=US05132295__ •
Biphasic release formations for lipophilic acids Inventor(s): Barnwell; Stephen G. (Chester, GB2) Assignee(s): Cortecs Limited (middlesex, Gb2) Patent Number: 5,391,377 Date filed: May 10, 1993 Abstract: A pharmaceutical formulation comprises: (a) a C.sub.12 -C.sub.24 fatty acid, which may be saturated or mono- or poly-unsaturated, such as oleic or linoleic acid; and (b) a generally lipophilic pharmaceutically active substance. A portion of the C.sub.12 C.sub.24 fatty acid is formulated for non-sustained release on non-parenteral administration and a portion of the C.sub.12 -C.sub.24 fatty acid and at least a portion of the pharmaceutically active substance are formulated for sustained release on nonparenteral administration. The pharmaceutically active substance may be a cardiovascular drug such as propranolol, verapamil, nifedipine, diltiazem, metoprolol, nicardipine or labetolol. Such formulations promote absorption redistribution of the active substance(s) from the hepatic portal blood supply to the lymphatic system, thereby avoiding first-pass liver metabolism. Formulations of this type will have a predictable dose response in patients, achieved with a lower chemical load, with which therapeutic efficacy is maintained. Excerpt(s): This invention relates to pharmaceutical formulations. In particular, the invention relates to a formulation for lipophilic drugs which may enhance the bioavailability of such drugs. Many lipophilic pharmaceuticals, such as cardiovascular drugs, are subject to an extensive yet variable "first-pass" metabolism. This occurs because orally administered drugs absorbed from the gastrointestinal tract are transported in the hepatic portal blood supply directly to the liver. Since the liver is the major site of drug metabolism, and lipophilic drugs are more prone to rapid metabolism, a major portion of an absorbed lipophilic drug may be prevented from reaching the systemic circulation. Classes of drugs to which this consideration particularly applies involve lipophilic beta-blocking agents and calcium channel blocking agents. However, other classes of lipophilic drugs suffer high hepatic first-pass metabolism. (iii) variability in the expression of drug metabolizing enzymes in children. Web site: http://www.delphion.com/details?pn=US05391377__
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Chiral nitriles, their preparation and their use for the manufacture of verapamil and analogues Inventor(s): McCague; Raymond (Cambridgeshire, GB), Wang; Shouming (Cambridge, GB) Assignee(s): Darwin Discovery Limited (gb) Patent Number: 5,910,601 Date filed: March 27, 1996 Abstract: The subject invention concerns a process for preparing a single enantiomer, either R or S, of R'--NH--(CH.sub.2).sub.3 --C(Ar)(CN)--R. The process is particularly useful for preparing verapamil, and analogues thereof, in single enantiomeric form. Excerpt(s): This invention relates to chiral compounds. In particular, it relates to a process for the manufacture of verapamil and analogues thereof, more particularly the manufacture of the single enantiomers thereof, and intermediates in that process. Verapamil is presently in clinical use as the racemate and is used extensively for treatment of hypertension. The (S)-isomer has the majority of the calcium channel antagonist activity, see DE-A-2059923, whilst the (R)-isomer differs in having sodium channel and other cell-pump actions in addition to a higher bioavailability, with slower clearance rate. For the treatment of hypertension, the (S)-isomer may provide a safer treatment than the racemate, with an extended therapeutic window. The (R)-isomer may be of benefit for the treatment of multidrug resistance in cancer chemotherapy, see J.F. Eliason, H. Ramuz and F. Kaufmann, Int. J. Cancer (1990) 46: 113-117; in this case hypotensive action by admixture with (S)-isomer would be undesirable. The preferential use of one of the isomers for migraine treatment is also possible, see S.J. Peroutka, Ann. Neurol. (1988) 23: 500-504. The preparation of the single enantiomers of verapamil is a difficult chemical problem. DE-A-3723654 discloses that the isomers have been separated by resolution with, for example, binaphthol bis (dihydrogen phosphate), but this would appear to be an expensive process. Similarly, the resolution of a racemic carboxylic acid precursor with brucine, as disclosed in DE-A-2059923, and the multi-step process thereafter, does not look attractive for bulk manufacture, nor does a lengthy synthesis from the enantiomers of propane-1,2-diol, see L.J. Theodore and W.L. Nelson, J. Org. Chem. (1987) 52: 1309-1315, or separation of the final product by chromatography, see JP-A-03027326. Web site: http://www.delphion.com/details?pn=US05910601__
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Combination preparation Inventor(s): Hahn; Klaus-Juergen (Heidelberg, DE), Kretzschmar; Rolf (Gruenstadt, DE), Lehmann; Hans D. (Hirschberg/Leutershausen, DE) Assignee(s): Basf Aktiengesellschaft (de) Patent Number: 4,798,811 Date filed: January 7, 1988 Abstract: A combination of verapamil, gallopamil or anipamil and acetylsalicylic acid in a weight ratio of from 10:1 to 2:1 being useful in the treatment of circulatory disorders. Excerpt(s): The present invention relates to a novel combination preparation for the treatment of disorders caused by thrombocyte aggregation. It is known that cardiac disorders due to an inadequate flow of blood through the tissue (ischemia) can be
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treated with verapamil, gallopamil and anipamil (cf. list in Pharma Index III/84, Isoptin.RTM. and Procorum.RTM. and European Laid-Open Application No. 64,158). These substances have both a vasodilating action and a cardioprotective and thrombocyte aggregation-inhibiting action. It is also known that, because of its thrombocyte aggregation-inhibiting action, acetylsalicylic acid is used for the prophylaxis of thromboembolic disorders (cf. list in Pharma Index III/84, Colfarit.RTM.). We have found that the action of verapamil, gallopamil and anipamil can be greatly increased by acetylsalicylic acid. Web site: http://www.delphion.com/details?pn=US04798811__ •
Composition and method for treating Peyronie's disease and related connective tissue disorders Inventor(s): Easterling; W. Jerry (8400 Blanco Rd., No. 204, San Antonio, TX 78216) Assignee(s): None Reported Patent Number: 6,031,005 Date filed: August 3, 1998 Abstract: The invention is of a topical medicament and associated methodology for use thereof, such that Peyronie's disease may be effectively, cost effectively, and painlessly treated. The primary active ingredient is a calcium channel blocker, the preferred such ingredient being verapamil. Excerpt(s): Applicant's invention relates to medicaments and treatment procedures relating to Peyronie's disease and related connective tissue maladies. The initial focus of the present invention--Peyronie's disease--has likely plagued men for time immemorial, but has been recognized as a distinct malady for no less than 400 years. Peyronie's disease was first described in 1743 by a French surgeon, Francois de la Peyronie. The disease was written about as early as 1687 and was oftentimes associated with impotence. Peyronie's disease often occurs in a mild form and heals spontaneously in 6 to 15 months. However, in severe cases, the hardened plaque substantially reduces penile flexibility and causes excruciating pain as the penis is forced into a highly arcuate or even serpentine configuration. A plaque on the top of the shaft (most common) causes the penis to bed upward; a plaque on the underside causes it to bend downward. In some cases, the plague develops on both top and bottom, leading to indentation and shortening of the penis. Web site: http://www.delphion.com/details?pn=US06031005__
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Composition for treating ocular pain Inventor(s): Belmonte-Martinez; Carlos (Alicante, ES), Gallar-Martinez; Juana (Alicante, ES), Gallego-Fernandez; Roberto (Alicante, ES), Pozo-Garcia; Miguel A. (Madrid, ES) Assignee(s): Universidad DE Alicante (alicante, Es) Patent Number: 5,525,601 Date filed: May 4, 1995 Abstract: The invention relates to the use of a calcium channel blocking agent for the manufacture of a medicament for alleviatirtg pain, such as ocular pain. Particular
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calcium channel blocking agents that can be used in accordance with the invention are diltiazem, verapamil, nifedipine, nicardipine, and nimodipine. Excerpt(s): This invention relates to the topical application of calcium channel blocking agents for treating ocular pain and neurogenic inflammation and compositions useful for such application. Pain is a well known phenomenon as an indicator of injury or tissue damage due to inflammation, ischemia, mechanical or other irritation [Juan, H., Prostaglandins as Mediators of Pain, Gen. Pharmacy, 9.403-409 (1978)]. The first step leading to the sensation of pain is the activation of nociceptive primary afferents by intense thermal, mechanical or chemical stimuli. Indirect studies of nociceptive transduction (activation) indicate that it involves chemical mediators that are released or synthesized in response to tissue damage [Fields, H. and Levine, J., Pain-Mechanisms and Management, Western Medical J. 141,347-357 (1984)]. These chemical mediators include lactic acid, hypertonic saline, histamine, 5-hydroxytryptamine, potassium chloride, acetylcholine, purines, bradykinin and substance P which are referred to as algesic agents (Juan, H., Supra). In recent years it has been shown that prostaglandins and leukotrines can contribute to the activation of primary afferent nociceptors (Fields, H. and Levine, J., Supra). Prostaglandins are uniquely distinguished from the other chemical mediators in that they induce a state of hyperalgesia by elevating the sensitivity of pain receptors to other painful or algasic stimuli. Web site: http://www.delphion.com/details?pn=US05525601__ •
Controlled absorption pharmaceutical composition Inventor(s): Geoghegan; Edward J. (Westmeath, IE), Panoz; Donald E. (Tuckerstown, BM) Assignee(s): Elan Corporation Plc (athlone, Ie) Patent Number: 4,863,742 Date filed: June 19, 1987 Abstract: A controlled absorption verapamil containing pellet formulation for oral adminstration comprises a core of a powder mixture containing verapamil or a pharmaceutically acceptable salt thereof and an organic acid and a polymeric material, said core comprising layers of said powder mixture and said polymeric material superimposed one upon the other and said polymeric material being present in an amount effective to ensure that all of said powder mixture is coated into said core and a multi-layer membrane surrounding said core, the number of layers in said membrane and the ratio of the various polymers comprising the membrane being effective to permit release of the verapamil from the pellet at a rate allowing controlled absorption thereof over a 24 hour period following oral administration, said rate being measured in vivo and having a Tmax between 6 and 16 hours. Excerpt(s): This invention relates to a verapamil pellet formulation for oral administration and the use thereof in the preparation of verapamil-containing pharmaceutical formulations which allow one to achieve a controlled absorption of verapamil in vivo. The invention relates, in particular, to a verapamil formulation suitable for once daily administration. It is an object of the present invention to provide a controlled absorption form of verapamil which is suitable for once daily administration, which is characterised by a high degree of absorption, which is substantially invariable from subject to subject, and by significant plasma levels of verapamil which are maintained for an extended period after administration. the
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number of layers in said membrane and the ratio of said water-soluble polymers to said water-insoluble polymers being effective to permit release of said verapamil from said pellet at a rate allowing controlled absorption thereof over a 24 hour period following oral administration, said rate being measured in vivo and having a Tmax between 6 and 16 hours. Web site: http://www.delphion.com/details?pn=US04863742__ •
Controlled release calcium channel blocker microcapsules Inventor(s): Powell; Thomas C. (West Alexandria, OH) Assignee(s): Eurand America, Inc. (oh) Patent Number: 5,252,337 Date filed: June 25, 1991 Abstract: A controlled release formulation of a calcium channel blocker for oral administration contains non-pareil seeds loaded with a calcium channel blocker, particularly diltiazem, nifedipine, or verapamil, and then microencapsulated in ethylcellulose by phase separation techniques. The resultant microcapsules provide an approximately zero order release rate, preferably over 12 to 16 hours. These microcapsules may be filled into gelatin capsules. Excerpt(s): This invention pertains to a sustained release formulation of calcium channel blockers microencapsulated by ethylcellulose and the process for preparing the formulation. Calcium channel blockers, such as diltiazem, nifedipine, and verapamil, modulate the transmembrane influx of calcium ions into both smooth and cardiac muscle. As the contractile processes of these muscles are dependent upon the movement of extracellular calcium ions into their cells, use of calcium channel blockers results in potent cardio-vascular effects. These results include decreased vascular resistance, slowed atrioventricular (A-V) conduction, reduced contractile tension, and reduced oxygen requirement of the heart muscle. Furthermore, the reduced calcium influx produced by calcium channel blockers interferes with excitation-contraction coupling of vascular smooth muscle, offering the therapeutic advantage of concomitant coronary and systemic vasodilation similar to the effect exerted by nitrates. Calcium channel blockers have been shown to be useful in alleviating symptoms of chronic heart disease, particularly cardiac arrythmias and essential hypertension. Calcium channel blockers are conventionally administered in tablet or capsule form. Recently, a patent for a sustained release tablet formulation of diltiazem has issued in which release rate is controlled by the application of a diffusion controlled membrane to a matrix tablet containing swellable hydrophilic polymers (U.S. Pat. No. 5,000,962, Sangekar, et al.). Other formulations of calcium channel blockers have also been patented. Ecanow suggests incorporation of veramapil hydrochloride into a coacervate-based, matrixenveloped composition (U.S. Pat. No. 4,963,367). Microcapsules of diltiazem are also suggested for injectable preparations. Okada, et al. prepare these microcapsules in a water-in-oil emulsion (U.S. Pat. No. 4,917,893 and Yamamoto, et al. prepare these microcapsules in a water-in-oil-in-water emulsion (U.S. Pat. No. 4,954,298). More recently, Debregeas, et al. disclose a slow release Galenical preparation of diltiazem (U.S. Pat. No. 4,960,596). Web site: http://www.delphion.com/details?pn=US05252337__
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Controlled release verapamil tablets Inventor(s): Baichwal; Anand R. (Wappingers Falls, NY), Staniforth; John N. (Bath, GB2) Assignee(s): Edward Mendell Co., Inc. (patterson, Ny) Patent Number: 5,169,639 Date filed: July 25, 1991 Abstract: Controlled release verapamil tablets are disclosed. The tablets include an excipient having a hydrophilic material, preferably containing a mixture of xanthan gum/locust bean gum, and an inert diluent. Excerpt(s): Many attempts have been made in the pharmaceutical art to provide a method by which therapeutically active medicaments can be directly tableted or mixed with a direct compression vehicle and thereafter directly tableted. Very few therapeutically active medicaments can be directly tableted due to unacceptable flow characteristics and compressible factors of the crystalline or powdered medicament, and also due to the small amounts of medicament needed to provide the desired effect. Therefore, it is a common practice to use an inert ingredient, i.e. excipients, diluents, fillers, binders and the like, such that the combination of the same with the medicament provides a material which can be directly compressed into tablets. In order to provide a directly compressible product, these excipients must have certain physical properties, including flowability, sufficient particle size distribution, binding ability, acceptable bulk and tap densities, and acceptable dissolution properties in order to release the medicament upon oral administration. U.S. Pat. No. 3,639,169 (Broeg, et al.) discloses one such direct compression vehicle for a therapeutically active medicament which consists of an insoluble or soluble diluent such as lactose dispersed in a matrix of hydrophilic hydratable high polymer such as hydrophilic polysaccharides, hydrocolloids or proteinaceous materials. The polymer, diluent and water are mixed and the resulting dispersion is dried, forming a film. The cooled film is fragmented, ground to the desired particle size and then blended with a desired medicament. Web site: http://www.delphion.com/details?pn=US05169639__
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Galenic forms of prolonged release verapamil and medicaments containing them Inventor(s): Baudier; Philippe (Waterloo, BE), De Boeck; Arthur (Herne, BE), Fossion; Jacques (Braine-L'Alleud, BE) Assignee(s): Pharlyse Societe Anonyme (luxembourg Ville, Lu) Patent Number: 4,832,958 Date filed: September 30, 1986 Abstract: The new galenic forms of prolonged release verapamil consist of microgranules containing a pharmacologically acceptable acid-addition salt or verapamil as active substance combined with at least one wetting agent, said microgranules being coated with a microporous membrane consisting of at least one pharmacologically acceptable adjuvant (such as plasticizer, filler, lubricant, etc) and of at least one film forming mixture composed of (1) at least one insoluble acrylic or methacrylic polymer and (2) a substance which is insoluble in the acid gastric medium, but soluble in the intestine. Excerpt(s): The hydrochloride of verapamil is used in medicine for its remarkable antagonistic properties against intracellular penetration of calcium. It is an important
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drug for the treatment of angina pectoris when the attack is associated with a coronary spasm and beta-adrenolytic products such as propanolol, timolol, atenolol and pindolol are liable to have undesirable effects. It is also useful in the treatment of hypertension and cardiac arrythmia. It is known to the man of the art that the pharmacological action of verapamil is proportional to its concentration in the plasma (Br. J. Clin. Pharmac. (1981), 12, 397-400) and that the optimum therapeutic range extends from 100 ng/ml to 400 ng/ml of plasma. The major disadvantage of treatment based on verapamil is that the half-life of this substance in the plasma is very short (2 to 4 hours) so that it requires the administration of several daily doses at intervals of only 6 hours. Such frequent administration renders the treatment difficult if not impossible to follow, especially during the night. Moreover, it has been found that after each administration of a quickrelease galenic form of verapamil, that is to say generally four times per day, there follows a succession of rapid increases and decreases in the plasma level. The whole organism and especially the organ to be treated, in this case the heart, are thus subjected to alterning overdoses and underdoses of the medicament. Web site: http://www.delphion.com/details?pn=US04832958__ •
Intracellular flush solution for preserving organs Inventor(s): Bretan, Jr.; Peter D. (Novato, CA) Assignee(s): The Cleveland Clinic Foundation (cleveland, Oh) Patent Number: 4,920,044 Date filed: November 8, 1988 Abstract: The present invention is directed to a new hypersomotic intracellular flush and storage solution for preserving an organ for transplantation. In addition, the present invention is directed to a method for preserving an organ to be transplanted by using the flush solution of the invention. Among the components of the solution are various physiologic salts, mannitol, adenosine, allopurinol and verapamil. Excerpt(s): The present invention relates to a new hyperosmotic intracellular flush and storage solution for preserving an organ for transplantation. In addition, the present invention relates to a method for preserving an organ to be transplanted by using an adenosine-MgSO.sub.4, mannitol intracellular flush solution. While the invention shall be described in connection with the preservation of kidneys, it is understood by those skilled in the art that the intracellular flush and storage solution disclosed herein and the preservation method utilizing the same are applicable to other organs such as the pancreas, the liver, and the heart. Recently, a great deal of progress has been achieved in the field of organ transplantation through the use of cyclosporine A. Cyclosporine A is a powerful immunosuppressive drug which appears to act mainly on T cells. Through the use of cyclosporine A, a 20% increase in one year allograft survival of kidneys has been noted over that of conventional therapy. However, this advantage appears to be lost with increasing preservation times of the organs to be transplanted (Opelz, G.: Multicenter Impact of Cyclosporin on Cadaver Kidney Graft Survival, Prog. Allergy 38: 329-345, 1986). In addition, there is increasing evidence that moderate ischemic injury based upon unsatisfied metabolic oxygen demand may predispose renal allografts to severe rejection and diminished survival (Keller, H., Fischer, G., Kirste, G., Wilms, H.: ATN Influence on Renal Transplant Function, Transpl. Proc. (in press) 1989). Thus, in today's cyclosporine era, better preservation techniques are essential for optimal allograft survival, not just to diminish the detrimental effects of prolonged preservation times, but also to prevent the occurrence of delayed graft function which is associated
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with further graft loss using cyclosporine prior to the complete resolution of post renal transplant acute tubular necrosis (Bia, M. J., Tyler, K. A.: Effect of Cyclosporine on Renalischemic Injury, Transplantation, 43:800-804, 1987). Web site: http://www.delphion.com/details?pn=US04920044__ •
Male contraceptives Inventor(s): Benoff; Susan H. (Riverdale, NY) Assignee(s): North Shore University Hospital (manhasset, Ny) Patent Number: 5,854,254 Date filed: August 23, 1996 Abstract: Methods for achieving human male contraception are described in which compounds that substantially inhibit the movement of mannose lectins on the surface of human male sperm cells are administered to human male patients, and the inhibition achieved provides a reversible infertility that can serve as a means of birth control. The use of calcium (Ca.sup.+2) ion channel blocking pharmaceutical compositions is described, particularly the drugs nifedipine, verapamil, and calcium ionophore A23187. Excerpt(s): This invention relates to methods for the use of drugs to substantially inhibit male fertility, and thus serve as useful male contraceptives. More specifically, the invention relates to the administration of calcium (Ca.sup.+2) ion channel blockers to substantially suppress sperm capacitation, and thereby substantially achieve reversible infertility in the human male. The incidence of male infertility in couples desiring conception has been estimated to be as great as 15% to 40% (11). Despite the great strides that have been made in understanding and treating infertility, one of the greatest difficulties has been the lack of adequate means to diagnose the existence, and potentially the cause, of the male contribution to such infertility. Methods for evaluating male infertility are currently limited to the assessment of a few general aspects of function (7,8) and these largely depend upon determining whether the sperm meets certain descriptive criteria. The most commonly relied-upon "classical" parameters of semen analysis are sperm number, motility and morphology, and ability to penetrate the cervical mucus (14). Unfortunately, when such parameters are analyzed by different laboratories, there are substantial variations in the results obtained (12,18,19). In addition, if samples of the same patient are tested repeatedly, the results can be substantially different, and the results can also vary considerably when tests from multiple samples of known fertile sperm are compared (20,21). Web site: http://www.delphion.com/details?pn=US05854254__
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Method and kit for testing tumors for drug sensitivity Inventor(s): Barranco, III; Sam C. (1005 Dartford Mews, Virginia Beach, VA 23452) Assignee(s): None Reported Patent Number: 5,366,885 Date filed: June 9, 1992 Abstract: Chemotherapy agents of interest are tested in untreated tumor cells and in tumor cells pretreated with buthionine sulfoximine (BSO) which reverses resistance related to elevated glutathione levels, and/or calcium channel blockers such as
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Verapamil which reduce resistance related to p-glycoprotein levels. The results of the several tests are then integrated to provide a predictor of tumor drug sensitivity and the potential utility of pretreatment regimens. Excerpt(s): This application relates to a method and kit for use in testing cells, and particularly tumor or leukemia cells, for drug sensitivity. Chemotherapy agents are frequently employed in treatment of many forms of cancer. The theory underlying the use of these agents, which are all extremely cytotoxic, is that they will be more harmful to the rapidly dividing tumor cells than to the patient as a whole. In some cases, however, a given tumor either proves to be initially resistant to the chemotherapy agents administered or develops resistance over the course of treatment. This resistance, whether natural or induced, cannot be overcome by simply increasing the dosage because this may unacceptably increase the harmful side effects of the agent to the patient, and it therefore becomes necessary to completely change the treatment regime. The harm to the patient from an aborted attempt at chemotherapy may be substantial. First, the patient has been physically injured to some extent by the administration of the chemotherapy agents and has not received much, if any, offsetting benefit. Second, in many cases, the cancer may progress during the period of ineffective treatment to a point where the therapy with the second-chosen group of agents comes too late to substantially prolong the patient's life. Accordingly, a method of determining the drug sensitivity profile of a given tumor prior to the administration of chemotherapy agents would be highly desirable. Web site: http://www.delphion.com/details?pn=US05366885__ •
Method for using verapamil for treating stroke Inventor(s): Marcoux; Frank W. (Ann Arbor, MI) Assignee(s): Warner-lambert Company (morris Plains, Nj) Patent Number: 4,654,372 Date filed: January 10, 1986 Abstract: The present invention is a method of use for the treatment of stroke with one of diltiazem, verapamil, or nifedipine. Excerpt(s): It is suggested in the literature, that pharmacologic agents are currently under study for cerebral resuscitation and such agents include calcium antagonists. See generally, N. G. Bircher, "Ischemic Brain Protection," Ann. Emerg. Med., 14:8 August 1985, pp 784-788 and S. E. Gisiold and P. A. Steen, "Drug Therapy in Brain lschaemia", Br. J. Anaesth., 57, (1985), pp 96-109. After a general disclosure of the value of calcium entry blockers in circulatory disorders results of selected clinical studies with flunarizine by A. Kappert, in "The Clinical Value of Calcium Entry Blockers in Circulatory Disorders. Effect of Flunarizine in Cerebro-Vascular and Peripheral Vascular Diseases," Inter. Angio., 3, 1984, pp 43-50, are said to show a positive, well documented effect on the symptoms of cerebrovascular insufficiency and on intermittent claudication in peripheral arteriosclerosis. Specific indications suggested by A. Kappert as a result of his clinical studies are migraine and vertigo. The mechanism of such effect and any significance for other calcium antagonists from these studies is not known and not predictive for the utility of the present invention, i.e., the treatment of occlusive stroke. ln fact, flunarizine is not active in the assay described hereinafter as the combined middle cerebral and ipsilatera]common carotid artery occlusion (MCAO) in the rat. This is essentially a well-recognized screen for compounds active against stroke now used to
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show the method of use for compounds havinq activity for the treatment of stroke of the present invention. Thus, although it is reported by J. K. Deshpande and T. Wielock in the article "Amelioration of Ischemic Brain Damage by Postischemic Treatment with Flunarizine, Neurological Research, 1985, Volume 7, March, pp 27-29, that flunarizine significantly reduced neuronal necrosis, the same authors readily admit that the etiologic processes involved in the damage that follows an ischemic insult still have not been clearly defined. ln fact, D. P. Reedy, et al, "Effects of Verapamil on Acute Focal Cerebral Ischemia," in Neurosurgery, Vol. 12, No. 3, 1983, pp 272-6, report that verapamil, that is also a Ca++ entry blocking agent, did not improve regional cerebral blood flow and did not protect ischemic brain in acute focal cerebral ischemia. J. R. Berger, et al, "Calcium Channel Blocker: Trial in Global Brain Ischemia," Neurology, p 183, 33[Suppl. 2]April 1983 also studied the efficacy of verapamil in preventing ischemic brain injury in rats concluding that the results of this study suggest that calcium channel blockers are ineffective in the treatment of several brain ischemia. Web site: http://www.delphion.com/details?pn=US04654372__ •
Method of treating diseases arising from platelet hyperactivation Inventor(s): Ahn; Yeon S. (Miami, FL), Harrington; William J. (Miami, FL), Haynes; Duncan H. (Miami, FL), Jy; Wenche (Miami, FL) Assignee(s): University of Miami (coral Gables, Fl) Patent Number: 4,728,660 Date filed: June 11, 1984 Abstract: Calcium (Ca.sup.2+) channel blockers, such as nifedipine and verapamil, are used in the treatment of thromboembolic diseases such as stroke and peripheral vascular occlusive diseases, especially arterial and venous thrombosis, vasculitis, myelofibrosis disease and hemolytic anemias. Such diseases arise from platelet hyperactivation and the Ca.sup.2+ channel blockers restore the platelets to their normal aggregation characteristics. Diagnostic procedures for detecting platelet hyperactivation and defective calcium handling/transport indicative of certain peripheral obstructive diseases using chlorotetracycline as a detectable fluorescent probe as a means of assessing a patient's response to Ca.sup.2+ channel blockers in the therapy of such diseases are also described. Excerpt(s): Current Therapy for Vascular Occlusive Diseases: Thrombosis and many related peripheral obstructive diseases are the result of abnormal activation of normal clotting mechanisms. Normal blood clotting is the result of a highly amplified chain reaction triggered by exposure of soluble factors and platelets to tissue factors, collagen and certain metabolites or hormones such as adenosine diphosphate (ADP), adrenaline and thromboxane. The clotting mechanism makes use of two systems: (a) soluble factors in the blood which activate each other in a serial manner causing hydrolysis of fibrinogen to fibrin which forms an insoluble crosslinked network, and (b) the circulating thrombocytes (platelets) which respond to the activating stimuli by releasing their own activators and by aggregating with each other. In normal clotting the soluble and platelet systems interact, with activation of one reinforcing the activation of the other. Abnormal activation of these systems can give rise to peripheral obstructive diseases. While the pathogenesis is very complex, current models involve a lesion of the vein or artery wall, local activation of the clotting system, recruitment of activated soluble factors and platelets into the region, homeostasis, local ischemia, and reinforced activation recruitment. The platelet plays a central role in the formation and extension of
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clot in both venous and arterial thrombosis. In venous thrombosis, the activation of platelet initiates shape changes and release reactions of platelet contents such ADP, arachidonic acid derivatives, clotting factors which promote platelet recruitment and aggregation and activate coagulation cascade leading to fibrin formation. The activated platelet also provides an activated surface (platelet factor III) which serves as a binding site for soluble clotting factors thereby increasing their interaction and further accelerating the rate of fibrin formation. Current therapy for venous thrombosis relies mainly on the inhibition of fibrin formation; little attention was given to inhibition of the platelet which plays central role in activation. Conventional therapy for venous thrombosis makes use of heparin which actively neutralizes several of the activated soluble clotting factors. Conventional therapy also makes use of the so-called "oral anticoagulants" (dicumarol and related compounds) which inhibit the synthesis of these factors. Direct platelet activation is not affected by these drugs. In arterial thrombosis, platelets adhere to injured or diseased vessel wall and transform their shapes, release ADP and other platelet granule content, convert arachidonic acid to thromboxane A.sub.2, which promotes more platelet aggregation and vasconstriction and consolidation of platelet plugs. The use of antiplatelet drugs is, therefore, the mainstay of treatment and prevention of arterial thrombosis. Two classes of drug target the platelet and are used to treat arterial thrombosis: aspirin and dipyridamole. Aspirin inhibits the activation of arachidonic acid, which is one of the pathways for platelet activation. This offers some protection against activation. Dipyridamole is a phosphodiesterase inhibitor which increases the platelets' cyclic AMP level. This offers further protection against activation. Web site: http://www.delphion.com/details?pn=US04728660__ •
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
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changes in bladder innervation and that these may be orchestrated by neurotrophic factors. Web site: http://www.delphion.com/details?pn=US05698549__ •
Method of treating liver disease and like indications with vasodilating agents Inventor(s): McLean; Allan Joseph (South Melbourne, AU) Assignee(s): Pharmacy and Therapeutic Advisory Consultancy Ltd. (london, Gb2) Patent Number: 5,854,233 Date filed: June 20, 1996 Abstract: Liver diseases, such as cirrhosis of the liver, toxic and medicamentary liver damage, a liver-parenchymic disorder or hepatitis, are treated by administering to a human or animal subject in need thereof a therapeutically active or prophylactically effective low dose amount of a vasodilating agent which selectively increases the supply of oxygenated blood to the liver by increasing hepatic arterial inflow. Suitable vasodilating agents include calcium blockers, such as a benzothiazepine derivative, nifedipine, felodipine or verapamil. Excerpt(s): The present invention relates to a method for the treatment of liver disease. The invention also relates to compositions suitable for the use in the treatment of liver disease. Diltiazem is the generic name given to the active component of a composition that is primarily used for the treatment of heart disease. Specifically it is known as 3acetoxy-5-(2(dimethylaminoethyl)-2,3-dihydro-2-(4-methoxy phenyl)-1,5benzothiazepine-4)5H-one. This compound is the active ingredient in the heart treatment drug Cardizem. Cardizem has particular efficacy in the treatment of ischaemic heart disease including angina pectoris and hypertension. Diltiazem is a member of a broad class of benzothiazepine derivatives that are the subject of Australian Patent 426146. The class of compounds are referred to in that specification as having particular utility as anti-depressants, tranquilizers and coronary vasodilators. Web site: http://www.delphion.com/details?pn=US05854233__
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Method of using nor-verapamil and nor-gallopamil as anti-arteriosclerotics Inventor(s): Mueller; Claus D. (Viernheim, DE), Unger; Liliane (Ludwigshafen, DE) Assignee(s): Knoll AG (ludwigshafen, De) Patent Number: 5,342,853 Date filed: November 12, 1991 Abstract: The use of nor-verapamil and nor-gallopamil and the salts thereof with physiologically tolerated acids is disclosed for the preparation of drugs with antiarteriosclerotic properties. Excerpt(s): The invention relates to the use of nor-verapamil (5-[N-(3,4dimethoxyphenethyl)-amino]-2-(3,4-dimethoxyphenyl)-2-isopropyl- valeronitrile) and nor-gallopamil (5-[N-(3,4-dimethoxyphenethyl)-amino]-2-(3,4,5-trimethoxyphenethyl)2-isop ropyl-valeronitrile) for the preparation of drugs with antiarteriosclerotic properties. Nor-verapamil is disclosed in the publication "Neugebauer, G., Cardiovasc.
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Rs. 1978, 12 (4) 247-254". Nor-gallopamil is described by M. Nieder and H. Jaeger in Journal of Chromatography 1987, 414, 492-498. Web site: http://www.delphion.com/details?pn=US05342853__ •
Methods and compositions for treating viral infections Inventor(s): Albrecht; Thomas (Galveston, TX), Steinsland; Odd S. (Galveston, TX) Assignee(s): Board of Regents, University of Texas System (austin, Tx) Patent Number: 4,663,317 Date filed: April 18, 1984 Abstract: The disclosure demonstrates the inhibition of replication of human cytomegalovirus (HCMV) in cultured human embryo skin muscle cells by two separate subclasses of direct-acting smooth muscle relaxing agents. These two subclasses are characterized mechanistically as calcium influx blockers (or calcium channel blockers) and cyclic nucleotide modulators. More specifically, the class of calcium influx blockers is exemplified by the drugs verapamil (and methoxyverapamil), nifedipine (the prototype drug of 1,4 dihydropyridines), and diltiazem. The class of cyclic nucleotide modulators is exemplified by the drugs isobutylmethylxanthine, papaverine (and its synthetic analog dioxyline), forskolin, and sodium nitroprusside. All of these agents inhibit replication of HCMV and HSV. Excerpt(s): The present invention relates to methods and compositions for treating viral infections. More specifically, the invention is directed towards the treatment of viral infections through the use of smooth muscle relaxing agents and agents that block the entry of calcium ions (Ca.sup.++) into cells. These agents appear to act by blocking replication of the target viruses in infected cells. Advances in the treatment of viral infections have been very slow in coming. Very few efficacious antiviral agents presently exist. A few agents have been touted for their potentially specific antiviral activity are in the research and development stage. The clinical efficacy of these agents, such as interferon and interferon inducers (e.g., polyanionic pyran copolymers and double stranded RNA) have yet to be reproducibly demonstrated. A few pharmaceutical agents have shown promise in the treatment of isolated viral infections, including the use of amantadine in the treatment of Influenza A.sub.2 strains. The use of the antimetabolities, Idoxuridine and Cytarabine, in antiviral therapy is hampered by a narrow spectrum of activity and potentially severe side effects. Methisazone is receiving some support for its use against some pox and vaccinia strains. Its use in pox infections is generally limited to prophylaxis. In general, there are presently no efficacious antiviral agents that demonstrate a broad spectrum of activity. It now appears that no single broad spectrum agent, or family of agents, may be identified as useful in antiviral treatment. Therefore, research is being directed towards identifying antiviral agents with activity against selected viral diseases. Web site: http://www.delphion.com/details?pn=US04663317__
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Noninvasive method for treating hemangiomas through transdermal delivery of calcium channel blocker agents and medicament for use in such method Inventor(s): Easterling; W. Jerry (8400 Blanco Rd., Ste. 204, San Antonio, TX 78216) Assignee(s): Easterling; W. Jerry (san Antonio, Tx) Patent Number: 6,627,663 Date filed: April 20, 2001 Abstract: The invention is of a noninvasive method for treating hemangiomas involving the topical application of verapamil suspended in a carrier through which penetration of verapamil is enhanced. Excerpt(s): The present invention relates to the treatment of hemangiomas. Hemangioma is the most common benign tumor of infants. They are usually apparent at birth but become evident within the first two weeks. Hemangiomas occur in 5-10% of all children and three times more often in females then males. Approximately thirty percent of all hemangiomas are visible at birth. The remaining seventy percent become visible within one to four weeks after birth. Hemangiomas occur 5 times more often in females than in males and occur predominantly in Caucasians. Low birthweight infants (less than 2.2 pounds) have a twenty six percent chance of developing a hemangioma. Web site: http://www.delphion.com/details?pn=US06627663__
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Novel galenic forms of verapamil, their preparation and medicines containing said novel galenic forms Inventor(s): Baudier; Philippe (Waterloo, BE), De Boeck; Arthur (Herne, BE), Fossion; Jacques (Braine-L'Alleud, BE) Assignee(s): Pharlyse Societe Anonyme (l-luxembourg Ville, Lu) Patent Number: 4,859,469 Date filed: September 18, 1986 Abstract: The invention relates to a novel galenic form of verapamil which show an excellent bioavailability. The novel galenic form comprises microgranules containing a verapamil addition salt with an acid, associated to at least one wetting agent. The microgranules are coated with a porous membrane constituted of a synthetic polymer associated to an adjuvant. Excerpt(s): The present invention relates to novel galenic forms of verapamil, their manufacture and medicines containing said novel galenic forms. Verapamil chlorhydrate is used in medicine in view of its outsetting properties as the calcium intracellular penetration antagonist. This characteristic makes from it an interesting medicine for the treatment of angor pectoris when the crisis or attack is bound to a coronary spasm and when undesirable effects of beta-adrenolytic products such as propranolol, timolol, atenolol and pindolol, are to be feared for. Said substance is also useful in the treatment of hypertension or too high blood pressure and of troubles of the cardiac rhythm. It is known from the skilled men that the pharmacological action of verapamil is proportional to its plasmatic concentration (Br. J. Clin. Pharmac. (1981), 12, 397-400) and that the optimum therapeutic zone is comprised between 100 ng/ml and 400 ng/ml of plasma. Web site: http://www.delphion.com/details?pn=US04859469__
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Pharmaceutical compositions containing non-racemic verapamil and process for optimizing the pharmaceutical activity of R- and S-verapamil Inventor(s): Fakhreddin; Jamali (Edmonton, CA), Longstreth; James A. (Mundelein, IL) Assignee(s): G. D. Searle & Co. (chicago, Il) Patent Number: 5,955,500 Date filed: May 23, 1997 Abstract: Pharmaceutical compositions containing non-racemic mixtures of verapamil are described, as well as a process of making pharmaceutical compositions containing unequal amounts of R- and S-verapamil.A process for customizing a pharmaceutical composition containing R-verapamil and S-verapamil to optimize a selected pharmaceutical activity comprises selecting a pharmaceutical activity possessed by Rverapamil or S-verapamil, alone or in combination, and then determining a target plasma level for R-verapamil and S-verapamil to achieve that activity is also described. A dosage form for administering the drug is selected. Based on dosage form, one determines the relative amounts of R- and S-verapamil to incorporate into the dosage form to achieve the targeted plasma levels. The dosage form can then be formulated. Excerpt(s): This invention uses the unequal pharmacological activities (both for toxic events and therapeutic events) and the different pharmacokinetics of the enantiomers of verapamil as a basis for customizing the administered verapamil enantiomer mixture to produce a desired verapamil enantiomer ratio in the plasma or serum of patients. Verapamil, benzeneacetonitrile,.alpha.-›3-››2-(3,4dimethoxyphenyl)ethyl!methylamino!propyl!-3,4-dimethox y-.alpha.-(1-methylethyl) hydrochloride, is a commercially available drug. It is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist). Current marketed verapamil dosage forms intended for cardiovascular therapy contain equal amounts of R-verapamil and Sverapamil. When administered intravenously this mixture produces circulating Rverapamil concentrations that are approximately twice the S-verapamil concentrations. When administered orally as an immediate release formulation, this mixture produces approximately a 3:1 R:S ratio in the systemic circulation; as an oral sustained release formulation the plasma ratio is approximately 5:1. Thus a single chemical composition produces chemically dissimilar plasma concentrations, and pharmacologically dissimilar effects depending on the route of administration, and the type of formulation used. Web site: http://www.delphion.com/details?pn=US05955500__
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Pharmaceutical drug dosage forms providing different release rates Inventor(s): Bardsley; Hazel Judith (Cambridge, GB), Gilbert; Julian Clive (Cambridge, GB), Richards; Andrew John McGlashan (Cambridge, GB) Assignee(s): Darwin Discovery Limited (gb) Patent Number: 6,056,968 Date filed: March 11, 1998 Abstract: A pharmaceutical dosage form comprises, in one portion thereof, a substantially single (+)-enantiomer of a chiral drug other than verapamil and, in another, separate portion thereof, a substantially single (-)-enantiomer of the drug wherein, in use, the different enantiomers are released at different rates from the dosage
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form. The dosage form is useful for administration of chiral drugs where both enantiomers have a valid pharmacological input, and where a clinical benefit may be realised by controlling the release rates of those enantiomers. Examples of such drugs include, in particular, tramadol and warfarin. Excerpt(s): This invention relates to the discovery of novel pharmaceutical dosage forms of chiral drugs. The separate enantiomers of some chiral drugs have different therapeutic properties, and/or mechanisms of action and yet in some cases it may still be desirable to dose both enantiomers together. However, where the pharmacokinetic properties of the separate enantiomers are different, for instance due to differences in the rates at which they are metabolised, the ratio of the different enantiomers changes with time after initial dosing, which can lead to reduced efficacy of the drug. The actual enantiomeric ratio at any one time may be dependent upon a number of factors, and may be further complicated if different dosage forms provide different enantiomeric ratios. Effects such as these have been observed with the different enantiomers of verapamil, for instance see Longstreth, J.A. Clin. Pharmacol. (1993) 18 (2nd Edition): 315-336 and Gupta et al., Eur. J. Pharm. Biopharm. (1996) 42(1): 74-81. According to the present invention, a pharmaceutical dosage form comprises, in one portion thereof, a substantially single (+)-enantiomer of a chiral drug other than verapamil and, in another, separate, portion thereof, a substantially single (-)-enantiomer of the drug, wherein, in use, the different enantiomers are released at different rates from the dosage form. Web site: http://www.delphion.com/details?pn=US06056968__ •
Process for the preparation of basically substituted phenylacetonitriles Inventor(s): Ahrens; Kurt H. (Nuremberg, DE), Grafe; Ingomar (Nuremberg, DE), Kisielowski; Lothar (Nuremberg, DE), Liebenow; Walter (Nuremberg, DE) Assignee(s): Ludwig Heumann & Co., Gmbh (de) Patent Number: 4,697,035 Date filed: June 3, 1985 Abstract: A simplified process for the preparation of basically substituted phenylacetonitriles, in particular of verapamil, is described. This process is carried out with fewer stages and higher yields than the known processes according to the state of the art. Excerpt(s): This invention relates to a process for the preparation of basically substituted acetonitriles. It is known that basically substituted phenyl acetonitriles have coronary vasodilator and antiarrhythmia properties and are therefore valuable medicaments for the treatment of various coronary diseases. The best known substance is.alpha.isopropyl-.alpha.-[(N-methyl-N-homoveratryl)-.gamma.-aminopropyl]3, 4dimethoxyphenylacetonitrile (verapamil, DE-PS No. 1 154 810). Various processes for the preparation of such basically substituted phenylacetonitriles have been disclosed in DE-PS No. 1 154 810, DE-PS No. 1 158 083, DE-OS No. 2 059 923, DDR-PS No. 119 579 and DE-OS No. 3 121 766. Web site: http://www.delphion.com/details?pn=US04697035__
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Products containing verapamil or gallopamil and prazosin Inventor(s): Tetzner; Christine (Ludwigshafen, DE) Assignee(s): Basf Aktiengesellschaft (ludwigshafen, De) Patent Number: 5,077,294 Date filed: April 13, 1990 Abstract: Products contain verapamil or gallopamil and prazosin, in each case in depot form, as a combination preparation for simultaneous use in the therapy of high blood pressure. Excerpt(s): It is known that verapamil (5-[N-3,4-dimethoxyphenethyl-N-methylamino]2-(3,4-dimethoxyphenyl)-2-isop ropylvaleronitrile), gallopamil (5-[N-3,4dimethoxyphenethyl-N-methylamino]-2-(3,4,5-trimethoxyphenyl)-2-i sopropylvaleronitrile) and prazosin (4-amino-2-[4-(2-furoyl)-piperazin-1-yl]-6,7dimethoxyquinazoline) have hypotensive properties (Therapiewoche 34 (1984) 7009, Brit. J. Clin. Pharmac. 21 (1986), 143 S, Drug Research 20 (1970), 799, medwelt 35 (1984), 1534 and Munch. med. Wschr. 127 (1985), 379). It is also known that a combination of verapamil and prazosin has superadditive properties (Clin. Pharmacol. Ther. 36 (1984), 716, and Br. J. Clin. Pharmac. 18 (1984), 290 P). However, the simultaneous administration of both substances or of a combination of the two substances leads to an excessive fall in blood pressure which is accompanied by orthostatic symptoms which occur more frequently than with prazosin alone (Clin. Pharmacol. Ther. 36 (1984), 716 (left-hand column)). We have found, surprisingly, that verapamil and gallopamil can be administered as a sustained release form together with prazosin. Web site: http://www.delphion.com/details?pn=US05077294__
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Resolution Inventor(s): Bannister; Robin Mark (Cambridge, GB), Evans; Graham Robert (Cambridge, GB), Skead; Benjamin Mark (Cambridge, GB) Assignee(s): Darwin Discovery Limited (gb) Patent Number: 5,892,093 Date filed: February 7, 1997 Abstract: A reproducible process for preparing a substantially single enantiomer (R or S) of 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexanoic acid, or an analogue thereof, thereby providing single enantiomer acid for the first time, proceeds by means of a classical salt resolution employing a resolving agent selected from an enantiomer (R or S) of a 1-arylalkylamine and (-)-quinine, and provides novel salts that are readily convertible to verapamil. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/016,536, filed May 7, 1996, and U.S. Provisional Application No. 60/016,987, filed May 7, 1996. The present invention relates to processes for the manufacture of single enantiomer and enantiomerically-enriched forms of verapamil precursors, and their use in the manufacture of verapamil. There is, therefore, a requirement for efficient processes to manufacture enantiomerically-enriched forms of verapamil and its analogues. This is a challenging endeavour since construction of the quaternary chiral centre with high asymmetric induction is difficult. Several synthetic routes have been
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published, but for a variety of reasons these are not suitable for operation on a large scale. Web site: http://www.delphion.com/details?pn=US05892093__ •
Resolution of racemic verapamil Inventor(s): Ehrmann; Oskar (Mannheim-Neuhermsheim, DE), Nagel; Herbert (Schifferstadt, DE) Assignee(s): Knoll Aktiengesellschaft (ludwigshafen, De) Patent Number: 5,457,224 Date filed: June 7, 1994 Abstract: A process for the resolution of racemic verapamil which comprises reacting the free base of the compound with optically active dibenzoyltartaric acid or ditoluoyltartaric acid in the molar ratio from 1:1 to 1:2 in a methanol/water mixture in the ratio from 1:1 to 3:1 or acetone/water mixture in the ratio from 0.5:1 to 2:1, separating the mixture of diastereomers obtained in this way by crystallization, and then converting the diastereomers into the free bases and these into their salts, if required, with physiologically tolerated acids. Excerpt(s): Verapamil [1,7-bis(3,4-dimethoxyphenyl)-3-methyl-aza-7-cyano-8methylnonane] has been disclosed in DE-C 1 154 810. It was for a long time not possible to resolve this racemic compound into the optical antipodes (Helv. Chim. Acta 58 (1975) 2050). It was therefore necessary to synthesize it from optically active precursors (DE-C 20 59 985, DE-C 20 59 923). By contrast, DE-A 3 723 684 describes a process for the resolution of racemic verapamil with the aid of R- or S-2,2'-(1,1'-binaphthyl)phosphoric acid. However, this substance is extremely costly to prepare so that economic preparation of the antipodes of verapamil continues to be impossible. It was necessary to assume from this prior art that resolution of racemic verapamil is very difficult and costly. Web site: http://www.delphion.com/details?pn=US05457224__
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Solid drug form with a high verapamil content Inventor(s): Flaig; Ernst (Heidelberg, DE), Fricke; Helmut (Mutterstadt, DE), Moest; Thomas (Moorrege, DE) Assignee(s): Knoll AG (ludwigshafen, De) Patent Number: 5,364,635 Date filed: July 27, 1993 Abstract: A solid drug form containing not less than 90% by weight verapamil is produced by granulating at from 30.degree. to 55.degree. C. with a little water, drying and, where appropriate, conventional tableting or by pelleting, in which case the granules obtained as described are, after cooling, moistened once again and compacted in a granulating mixer at from 30.degree. to 55.degree. C. and are dried. Excerpt(s): The present invention relates to solid drug forms with a distinctly higher verapamil hydrochloride content than previously possible, and to processes for the production thereof. The maximum content of verapamil in commercial verapamil
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tablets and cores of film-coated tablets is 70%. The highest concentration reported is just about 80% (EP-A 217 778). Higher concentrations cannot be attained because, in the granulating stage necessary before tableting, verapamil tends to become gummy in the granulating equipment and, even after drying, is difficult to form into tablets because this tendency also results in adhesion to the die of the tablet press. Direct tableting of commercial verapamil in high concentration (more than 70%) without previous granulation fails because of the poor flowability of the commercial raw material, the deficient binding ability despite the addition of readily deformable auxiliaries such as microcrystalline cellulose, and the tendency to become gummy and adhere under high compressive forces. Because of the relatively large amounts of active compound and added auxiliaries required, verapamil tablets, especially tablets with a coating to delay release, are relatively large and thus unpleasant to swallow. Web site: http://www.delphion.com/details?pn=US05364635__ •
Sustained release formulation containing three different types of polymers Inventor(s): Pinnamaraju; Prasad (Edison, NJ), Zhang; Guohua (Parsippany, NJ) Assignee(s): Hallmark Pharmaceuticals, Inc. (somerset, Nj) Patent Number: 5,695,781 Date filed: March 1, 1995 Abstract: Verapamil depot drug formulations include the pharmaceutical itself and a three component release rate controlling matrix composition. The three components of the matrix composition are (1) an alginate component, such as sodium alginate, (2) an enteric polymer component, such as methacrylic acid copolymer, and (3) a pH independent gelling polymer, such as hydroxypropyl methylcellulose or polyethyleneoxide. The drug release rate can be adjusted by changing the amount of one or more of these components of the composition. Excerpt(s): The present invention is directed to formulations for preparing sustained release drug forms useful for releasing pharmaceuticals at controlled rates, generally in the stomachs and/or gastrointestinal tracts of hosts. In particular the invention relates to an improved depot drug form useful in connection with preparing sustained release tablets. A zero order release profile for a drug from its controlled release dosage form sometimes is desirable in clinical use. The technology used to formulate zero order release dosage forms is well documented. The entrapment of a drug in a matrix is a common approach to formulate sustained release tablets with a zero order release profile. It has been reported that depot drug formulations for controlled release of pharmaceutical drugs may be prepared using alginates alone (see U.S. Pat. No. 5,132,295), using combinations of alginates and polyacrylates (see U.S. Pat. No. 5,230,901) and using combinations of alginates and a pH independent hydrocarbon gelling agent, such as, for example, hydroxypropylmethyl cellulose (see U.S. Pat. No. 4,792,452). It is also known that the use of alginates alone for this purpose often presents difficulties in tableting, film coating and storage. Web site: http://www.delphion.com/details?pn=US05695781__
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Sustained release pharmaceutical composition free of food effect Inventor(s): Seth; Pawan (Irvine, CA) Assignee(s): Pharma Pass Llc (irvine, Ca) Patent Number: 6,368,628 Date filed: May 26, 2000 Abstract: The invention provides a sustained release composition free of food effect comprising a core comprising an active agent except for carbamazepine or verapamil, and a coating comprising, based on the weight of the coating, from 30 to 80% of a gastroresistant polymer and from 10 to 40% of a hydrophilic silicon dioxide. The invention also provides a method of alleviating food effect in a pharmaceutical composition. The invention also provides a dispersion useful thereof. Excerpt(s): Food effect is a well-known phenomenon that can adversely affect the pharmacokinetics of drug distribution in the body. As a result, many drugs have to be taken either in fasted or fed conditions to achieve the optimum effect. Well known examples include carbamazepine tablets (to be taken with meals), captopril tablets (to be taken one hour before meals), or azithromycin tablets (to be taken 2 hours after meal), while some other drugs remain unaffected by food, as amoxicillin for example. For this reason, FDA recommends to test bioequivalency of drug products either under fasted or fed conditions, depending on the drug. Moreover, in the latter case the meal itself is standardized. Little formulation work has been conducted to date in order to overcome this food effect disadvantage. Web site: http://www.delphion.com/details?pn=US06368628__
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Therapeutic uses of verapamil enantiomers Inventor(s): Greaves; Jane Lizbeth (Cambridge, GB), Harding; Deborah Phyllis (Cambridge, GB) Assignee(s): Darwin Discovery Limited (gb) Patent Number: 5,932,246 Date filed: August 6, 1997 Abstract: Substantially single enantiomer (R or S) verapamil, or a pharmaceuticallyacceptable salt thereof provides an improved treatment for patients having a condition susceptible to treatment with racemic verapamil and who are disposed to constipation. Excerpt(s): This invention relates to improved treatment of patients having conditions which are susceptible to treatment with racemic verapamil, but who are disposed to constipation as a side effect thereof. The opposite enantiomers of verapamil have different biological activities and different potencies. The pharmacological profile is determined by stereoselectivity of pharmacodynamics and pharmacokinetics. The (R)enantiomer may be of benefit for the reversal of multi-drug resistance in cancer chemotherapy (see Eliason, Int. J. Cancer (1990) 46: 113). Web site: http://www.delphion.com/details?pn=US05932246__
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Treatment of low-tension glaucoma by topical administration of calcium channel blocking agents Inventor(s): Abelson; Mark B. (26 Phillips St., Andover, MA 01810) Assignee(s): None Reported Patent Number: 5,435,998 Date filed: August 3, 1994 Abstract: Low-tension glaucoma is treated by topical administration to the eye of an amount of a calcium channel blocking agent effective to increase blood flow to the optic nerve head. Calcium channel blocking agents of Class I are especially useful, and among these a preferred agent is verapamil hydrochloride. Excerpt(s): This invention relates to treatment of low-tension glaucoma by topically administered medications and more particularly to treatment of low-tension glaucoma by topical administration of calcium channel blocking agents. Low-tension glaucoma is an ophthalmic condition in which the symptoms and ophthalmic pathology, i.e., loss of visual fields, loss of visual acuity and contrast sensitivity, cupping of the optic disk, etc., are present in the eye, but the intraocular pressure (IOP) is normal or only slightly elevated. It is distinguishable from primary open angle glaucoma, which is characterized by an elevated IOP. The etiology of the disease is not well understood and consequently there is no consensus as to a medicinal course of therapy. While available topical therapy may lower IOP, it is not been conclusively demonstrated to alter beneficially the course of the disease. Consequently, certain topical medications have been used in an attempt to delay the progression of ophthalmic deterioration or even partially reverse the course of the disease. Nevertheless, conventional ophthalmic medications that lower the IOP have been used in an attempt to maintain the IOP as low as possible, even somewhat below the range usually considered as normal. Systemic drugs that increase the blood flow to the optic nerve head and/or retina have been found to have some effect in alleviating the loss of visual function in low-tension glaucoma. In particular, systemic, e.g., oral, administration of calcium channel blocking agents has been found on occasion to be of benefit in low-tension glaucoma. However, the systemic administration of vasoactive drugs in order to treat a condition of the optic nerve head and/or retina is subject to the evident disadvantage that it is difficult to attain sufficient ocular concentration without inducing systemic adverse side effects. Hitherto it has not been known to increase blood flow to the optic nerve head and/or retina and thereby arrest or alleviate the deterioration associated with low-tension glaucoma by topical administration of drugs to the eye. Web site: http://www.delphion.com/details?pn=US05435998__
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Treatment of ocular hypertension with class I calcium channel blocking agents Inventor(s): Abelson; Mark B. (26 Phillips St., Andover, MA 01810) Assignee(s): None Reported Patent Number: 4,981,871 Date filed: May 15, 1987 Abstract: Elevated intraocular pressure in a mammalian eye is lowered by administering to the eye an amount of a Class I calcium channel blocking agent effective to lower the
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elevated intraocular pressure. A preferred calcium channel blocking agent is verapamil and the preferred mode of administration is topical directly to the eye, e.g., with drops. Excerpt(s): Chronically elevated intraocular pressure ("IOP") is a condition which can cause damage to the tissues of the eye leading ultimately to loss of vision in the affected eye. The disease is generally due to an impediment in the outflow of aqueous humor from the eye, and in most cases, the ultimate cause of the condition is unknown. Nevertheless, in the common type of open-angle glaucoma, a number of types of drugs have been found useful in lowering and controlling elevated intraocular pressure. Timolol, an alpha.sub.1 - and alpha-.sub.2 -adrenergic receptor antagonist, has been topically administered as a 0.25% and 0.5% solution. Betaxolol, a beta.sub.1 -adrenergic receptor antagonist, has been used topically as a 0.5% solution. Pilocarpine, a cholinergic stimulating drug, has been topically instilled into the eye in the form of the chloride or nitrate salt in a 1% to 4% solution, to control elevated intraocular pressure. Echothiophate iodide (0.03% and 0.06%), a cholinesterase antagonist, and epinephrine (1% and 2%), an alpha- and beta-adrenergic agonist, have also been used topically to control intraocular pressure. Acetazolamide, a carbonic anhydrase inhibitor, has been administered orally (250 mg tablets) to control intraocular pressure by decreasing the secretion of aqueous humor by the ciliary body. However, these drugs are not free from side effects, and some are effective only for a time, which can present problems since therapy must be lifelong. Some interest has been expressed in the possibility of using calcium channel blocking agents for the treatment of glaucoma, but no demonstration has been made of their effectiveness. Web site: http://www.delphion.com/details?pn=US04981871__ •
Treatment of vascular disorders of the posterior segment of the eye by topical administration of calcium channel blocking agents Inventor(s): Abelson; Mark B. (26 Phillips St., Andover, MA 01810), Giovanoni; Richard L. (220 Richmond St., E. Taunton, MA 02718) Assignee(s): None Reported Patent Number: 5,431,907 Date filed: August 3, 1994 Abstract: Ischemic disorders of the retina and associated tissues of the posterior segment of the eye are treated by topical administration to the eye of an amount of a calcium channel blocking agent effective to increase blood flow to those tissues. Calcium channel blocking agents of Class I are especially useful, and among these a preferred agent is verapamil hydrochloride. Excerpt(s): This invention relates to treatment of diseases and/or disorders of the posterior segment of the eye and more particularly to the treatment of disorders arising from a decrease or failure of blood perfusion to the posterior ocular structures. The mammalian eye is a generally spherical structure that performs its visual function by forming an image of an exterior illuminated object on a photosensitive tissue, the retina. The basic supporting structure for the functional elements of the eye is the generally spherical tough, white outer shell, the sclera, which is comprised principally of collagenous connective tissue and is kept in its spherical shape by the internal pressure of the eye. The anterior portion of the sclera supports and contains the elements that perform the function of focusing the incoming light, i.e., the cornea and crystalline lens, and the function of regulating the intensity of the light entering the eye, i.e., the iris. The
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posterior portion of the globe supports the retina and associated tissues. In the posterior portion of the globe immediately adjacent the interior surface of the sclera lies the choroid, a thin layer of pigmented tissue liberally supplied with blood vessels. The portion of the choroid adjacent its interior surface is comprised of a network of capillaries, the choriocapillaris, which is of importance in the supply of oxygen and nutrients to the adjacent layers of the retina. Immediately within the choroid lies the retina, which is the innermost layer of the posterior segment of the eye and receives the image formed by the refractive elements in the anterior portion of the globe. The photoreceptive rod and cone cells of the retina are stimulated by light falling on them and pass their sensations via the retinal ganglia to the brain. Retinal function and health is dependent on two independent blood supplies. The outer portion of the retina, adjacent to the choroid, is nurtured primarily by the choriocapillaris of the choroid, while inner retinal layers receive their blood supply mainly via branches of the central retinal artery. Accordingly, both blood supplies are must be intact for proper perfusion of the retina, and one of them cannot substitute for the other. Web site: http://www.delphion.com/details?pn=US05431907__ •
Verapamil dosage form Inventor(s): Hamel; L. G. (Sunnyvale, CA), Stephens; Sally I. (Mt. View, CA) Assignee(s): Alza Corporation (palo Alto, Ca) Patent Number: 4,753,802 Date filed: March 19, 1986 Abstract: An osmotic dosage form comprising verapamil and mannitol in a nonequilibrium ratio. Excerpt(s): This invention pertains to both a novel and useful dosage form comprising the beneficial drug verapamil for administering it to a recipient. Verapamil is an ionic calcium influx inhibitor more commonly known as a calcium channel blocking agent. The principal pharmacologic and physiologic action of verapamil is to inhibit the transmembrane influx of extracellular calcium ions across the membrane of myocardial cells and vascular smooth muscle cells. By inhibiting calcium influx, verapamil inhibits the contractile processes of cardiac and vascular smooth muscles, thereby dilating the main coronary and systemic arteries. The drug is indicated and approved by the Food and Drug Administration for the management of unstable or chronic stable angina pectoris for the treatment of supraventricular tachyarrhythmias, and for the temporary control of rapid ventricular rate in arterial flutter or atril fibrillation. Verapamil is administered generally as its pharmaceutically acceptable addition salt. Orally administered verapamil is absorbed from the gastrointestinal tract. The prior art administers verapamil orally for the indicated cardiovascular indications in tablet form. Currently, verapamil is administered orally as tablets three or four times daily. While these conventional tablet forms are used for the indicated therapy, a fundamental limitation common to tablets is their temporal pattern of drug delivery. That is, they give up their drug to surrounding tissues and fluids at varying rates that are highest initially and then declines continually thereafter. For a therapeutically important cardiovascular drug such as verapamil, this sawtooth pattern of delivery of high-dose, low-dose variation of the needed drug presents drug to the tissues and then denies drug to the tissues, leading to unacceptable therapy. Also, within the intervals between doses, and with longer intervals between doses, there is a greater amplitude of the dosage cycle leading to irregularity of drug bioavailability and uncontrolled therapy.
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Web site: http://www.delphion.com/details?pn=US04753802__
Patent Applications on Verapamil 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 verapamil: •
Compositions for prevention and alleviation of skin wrinkles Inventor(s): Ahn, Ho-Jeong; (Daejeon, KR), Kim, Moon-Moo; (Daejeon, KR), Kim, SangNyun; (Daejeon, KR), Lee, Hak-Mo; (Daejeon, KR), No, Kyung-Ok; (Chungbuk, KR) Correspondence: Albert Wai Kit Chan; Law Offices OF Albert Wai Kit Chan; World Plaza Suite 604; 141 07 20th Avenue; Whitestone; NY; 11357; US Patent Application Number: 20040052750 Date filed: June 19, 2003 Abstract: The present invention discloses a topical composition for prevention and alleviation of wrinkling which comprises one or two or more selected from the group consisting of Phenytoin, Valproic acid, Cyclosporin A, Nifedipine, Diltiazem, Verapamil HCl and Amoldipine as an active ingredient having an effect of boosting collagen synthesis. Excerpt(s): The present invention relates to a topical composition for prevention and alleviation of skin wrinkles which comprises one or two or more selected from the group consisting of phenytoin, valproic acid, cyclosporine A, nifedipine, diltiazem, verapamil HCl and amoldipine as an active ingredient having an effect of promoting collagen synthesis, in conjunction with conventional components of a formulation for transdermal absorption such as cream, ointment, lotion, skin tonic, gel, pack, patch or patch-type administering apparatus. Skin aging is developed by both endogenous causes, for example, aging, and environmental causes. The effects of aging are shown as wrinkles in the skin, which include neck wrinkles, worry lines, frown lines, crow's feet, the folds from the side of the nose to the corners of the mouth, and fine lines around the eyes, below the lips, and over the face. Skin wrinkles caused by aging, though there are individual differences, commonly occur in individuals in their early twenties and increase with age. With aging, the amount of dermal collagen of skin is decreased and alterations in elastic fibers occur, whereby the skin relaxes and fine wrinkles appear. Meanwhile, collagen is a major matrix protein produced by fibroblasts of the skin, being present in the extracellular matrix. It is a primary protein comprising 30% by weight of proteins in the human body, and has a firm structure of a triple helix. It is known that collagen functions to provide structural stability to the skin, durability of connective tissues and cohesion of tissues while supporting cell coherence, cell proliferation, and induction of differentiation of unspecialized cells. Also, it is known that collagen is broken down by exposure to UV, an environmental cause of skin aging, and the damage by UV is proportional to the accumulated time of exposure thereto. UV denatures collagenous fibers, causing wrinkles and decreasing elasticity of the skin. Other environmental causes known to promote skin aging include wind, heat and smoking. As mentioned above, collagen is closely related with skin aging. The amount of collagen in
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This has been a common practice outside the United States prior to December 2000.
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the dermis is decreased with aging and by UV radiation. Collagen decreases by 65% from age 20 to age 80. Such a decrease of collagen makes the skin thin and further, is closely associated with the formation of skin wrinkles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Controlled release oral dosage form Inventor(s): Chen, Chih Ming; (Davie, FL), Cheng, Xiu Xiu; (Davie, FL), Tian, Dacheng; (Miramar, FL) Correspondence: Martin P. Endres, ESQ.; Hedman & Costigan, P.C.; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20040005359 Date filed: June 27, 2002 Abstract: A sustained-release pharmaceutical preparation is disclosed in which a calcium channel blocker, preferably verapamil, core is surrounded by an optional seal coat layer and a water-insoluble coating. Excerpt(s): The present invention relates to oral controlled release dosage formulations containing a calcium channel blocking agent. More specifically, the present invention relates to an oral dosage formulation in the form of a coated single composition core tablet comprising a calcium channel blocking agent, such as amlodipine, diltiazem, nicardipine, nifedipine, verapamil, felodipine, isradipine, nisoldipine, nimodipine, nilvadipine, flunarizine, norverapamil, nitredipine, cinnarizine, fendiline or their pharmaceutically acceptable derivatives, salts and stereoisomers. Preferably, the calcium channel blocking agent is verapamil. Verapamil (+/-)-5-[(3,4Dimethoxyphenethyl)methylamino]-2-(3,4-dime- thoxyphenyl)-2-isopropylvaleronitrile monohydrochloride or iproveratril is a nondihydropyridine calcium channel blocking agent that inhibits the transmembrane influx of extracellular calcium ions across the membranes of the myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations. By inhibiting calcium influx, verapamil inhibits the contractile processes of cardiac and vascular smooth muscle, thereby dilating the main coronary and systemic arteries. Verapamil is a class IV antiarrhythmic. It reduces afterload and myocardial contractility. Verapamil is used orally to treat Prinzmetal variant angina and unstable and chronic stable angina pectoris, the management of hypertension, for the prevention of recurrent premature supraventricular tachycardia (PSVT) and, in combination with a cardiac glycoside, to control ventricular rate at rest and during stress in patients with atrial flutter and/or fibrillation. It has been used as adjunctive therapy in the management of hypertrophic cardiomyopathy or in certain patients after myocardial infarction when beta-adrenergic blocking agents are ineffective or contraindicated for the relief of ongoing ischemia. Benefit has also been demonstrated in the management of manic manifestations of bipolar disorder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Delivery of anti-migraine compounds through an inhalation route Inventor(s): Rabinowitz, Joshua D.; (Mountain View, CA), Zaffaroni, Alejandro C.; (Atherton, CA) Correspondence: Richard R. Eckman; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030021754 Date filed: May 20, 2002 Abstract: The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing lidocaine, verapamil, diltiazem, isometheptene, or lisuride that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of lidocaine, verapamil, diltiazem, isometheptene, or lisuride. In a method aspect of the present invention, one of lidocaine, verapamil, diltiazem, isometheptene, or lisuride is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of lidocaine, verapamil, diltiazem, isometheptene, or lisuride, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering lidocaine, verapamil, diltiazem, isometheptene, or lisuride through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of lidocaine, verapamil, diltiazem, isometheptene, or lisuride; and, b) a device that forms a lidocaine, verapamil, diltiazem, isometheptene, or lisuride containing aerosol from the composition, for inhalation by the mammal. Excerpt(s): This application claims priority to U.S. provisional application Ser. No. 60/294,203 entitled "Thermal Vapor Delivery of Drugs," filed May 24, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. This application further claims priority to U.S. provisional application Ser. No. 60/317,479 entitled "Aerosol Drug Delivery," filed Sep. 5, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. The present invention relates to the delivery of anti-migraine compounds through an inhalation route. Specifically, it relates to aerosols containing lidocaine, verapamil, diltiazem, isometheptene, or lisuride that are used in inhalation therapy. There are a number of compositions currently marketed for the treatment of migraine headaches. The compositions contain at least one active ingredient that provides for observed therapeutic effects. Among the active ingredients given in such anti-migraine compositions are lidocaine, verapamil, diltiazem, isometheptene, and lisuride. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Epoxy-steroidal aldosterone antagonist and calcium channel blocker combination therapy for treatment of congestive heart failure Inventor(s): Schuh, Joseph R.; (St. Louis, MO) Correspondence: Pharmacia Corporation; Corporate Patent Law Department; Mail Zone O4e; 800 North Lindbergh BLVD.; ST. Louis; MO; 63167; US Patent Application Number: 20020042405 Date filed: July 27, 2001
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Abstract: A combination therapy comprising a therapeutically-effective amount of an epoxy-steroidal aldosterone receptor antagonist and a therapeutically-effective amount of a calcium channel blocker is described for treatment of circulatory disorders, including cardiovascular disorders such as hypertension, congestive heart failure, cirrhosis and ascites. Preferred calcium channel blockers are those compounds having high potency and bioavailability. Preferred epoxy-steroidal aldosterone receptor antagonists are 20-spiroxane steroidal compounds characterized by the presence of a 9.alpha.,11.alpha.-substituted epoxy moiety. A preferred combination therapy includes the calcium channel blocker verapamil HCl (Benzenacetonitrile, (.+-.)-.alpha.[3[[2-(3,4dimethoxyphenyl) ethyl]methylamino]propyl]-3,4-dimethoxy-.alpha.-(1methylethyl)hydrochlor- ide) and the aldosterone receptor antagonist epoxymexrenone. Excerpt(s): Combinations of an epoxy-steroidal aldosterone receptor antagonist and a calcium channel blocker are described for use in treatment of circulatory disorders, including cardiovascular diseases such as hypertension, congestive heart failure, cardiac hypertrophy, cirrhosis and ascites. Of particular interest are therapies using an epoxycontaining steroidal aldosterone receptor antagonist compound such as epoxymexrenone in combination with a calcium channel blocker compound. Myocardial (or cardiac) failure, whether a consequence of a previous myocardial infarction, heart disease associated with hypertension, or primary cardiomyopathy, is a major health problem of worldwide proportions. The incidence of symptomatic heart failure has risen steadily over the past several decades. In clinical terms, decompensated cardiac failure consists of a constellation of signs and symptoms that arises from congested organs and hypoperfused tissues to form the congestive heart failure (CHF) syndrome. Congestion is caused largely by increased venous pressure and by inadequate sodium (Na.sup.+) excretion, relative to dietary Na.sup.+ intake, and is importantly related to circulating levels of aldosterone (ALDO). An abnormal retention of Na.sup.+ occurs via tubular epithelial cells throughout the nephron, including the later portion of the distal tubule and cortical collecting ducts, where ALDO receptor sites are present. 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 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.
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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 •
Ningalin b analogs employable for reversing multidrug resistance Inventor(s): Boger, Dale L; (La Jolla, CA) Correspondence: The Scripps Research Institute; Office OF Patent Counsel, Tpc-8; 10550 North Torrey Pines Road; LA Jolla; CA; 92037; US Patent Application Number: 20030220320 Date filed: November 7, 2002 Abstract: Anlogs of ningalin B lacking inherent cytotoxic activity may be employed to reverse multi-drug resistant (MDR) phenotype and to resensitize transformed cells, including a human colon cancer cell line (HCT116/VM46), with respect to a variety of cytotoxic agents, e.g., vinblastine and doxorubicin. In many instances, resensitization is achieved at lower doses than the prototypical agent verapamil. Total synthesis of ningalin B and its analogs was achieved using a concise, efficient approach based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine.fwdarw. 1,2diazine.fwdarw. pyrrole) ideally suited for construction of the densely functionalized pyrrole core found in the natural product is detailed. Excerpt(s): The invention relates to methods and reagents for reversing multidrug resistance (MDR) with respect to anticancer drugs. More particularly, invention relates to analogs of ningalin B and to their use as MDR reversal agents. What is needed is a new class of MDR reversal agents having potent activity for resensitizing resistant cancer cells with respect to effective anticancer agents. A concise total synthesis of ningalin B (1) is described enlisting a 1,2,4,5-tetrazine.fwdarw. 1,2-diazine-pyrrole DielsAlder strategy featuring the unusually effective [4+2] cycloaddition of the electrondeficient 1,2,4,5-tetrazine 2 with an unsymmetrical, electron-rich alkyne. Ningalin B is a member of a class of marine natural products characterized by a highly functionalized tetra- or pentasubstituted pyrrole which is ideally suited to construction using this strategy. While lacking inherent cytotoxic activity, the ningalin B synthetic precursors 10, 11, 13, 14, and 15, but not ningalin B itself, are shown to potently reverse MDR,
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resensitizing a resistant human colon cancer cell line (HCT116/VM46) to vinblastine and doxorubicin. These agents, including 14 bearing a novel ring system, constitute the members of a new class of effective MDR reversal agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Oral drug composition containing a verapamil derivative as a drug-absorption promotor Inventor(s): Woo, Jong-Soo; (Kyungki-do, KR), Yoo, Sung-Eun; (Daejeon, KR) Correspondence: David A. Einhorn, ESQ.; Anderson Kill & Olick, P.C.; 1251 Avenue OF The Americas; New York; NY; 10020; US Patent Application Number: 20020049158 Date filed: May 11, 2001 Abstract: The bioavailability of a drug which is not readily absorbed in the digestive tract can be greatly enhanced by administering an oral composition comprising a drug and a compound of formula (I): 1wherein,X is CN, COOH, COOR.sup.10(wherein R.sup.10 is C.sub.1-2 alkyl), SO.sub.2Ph or SPh;k, l, m and n are each independently an integer of 0 to 4;R.sup.1 is H or C.sub.1-3 alkyl; andR.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are each independently EI, OHT or C.sub.1-3 alkoxy. Excerpt(s): The present invention relates to an improved oral composition of a drug which by itself is not readily absorbed in the digestive tract, said composition comprising the drug and a verapamil derivative which does not cause any adverse side effects. Drugs which are not readily absorbed in the digestive tract include many anticancer agents, e.g., actinomycin D, doxorubicin, daunomycin, vincri stifle, vinblastine, colchicine, paclitaxel, docetaxel, etoposide and hydroxyrubicin; immunosuppressive agents, e.g., cyclosporn A and FK-506; and hypotensive agents, e.g., verapamil and nicardipine. These drugs, which are generally administered by injection, arc not effective when orally administered due to the inhibitive action of p-glycoprotein present in the intestinal wall(Wacher, V. J. et at., Advanced Drug Delivery Reviews, 20, p99112(1996), anld Sparreboom, A. et al., Proc. Natl. Acad. Sci., 94, p2031-2035(1997)). Paclitaxel, a representative of such drugs, is absorbed only to the extent of 1% or less when orally administered. Because it is sparingly soluble in water, a typical injection formulation thereof is prepared by employing a 1:1 (v/v) mixture of ethanol and Cremophor.RTM. EL. However, such an injection formulation must be administered over a long period of time, often with other medication, so as to avoid possible adverse hypersensitive allergic reactions caused by Cremophor.RTM. EL. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preservation of blood platelets at cold temperatures Inventor(s): Lucas, David; (Lafayetta, CA), Serebrennikov, Vladimir; (Krasnoyarsk, RU), Toledo, Luis H.; (Portage, MI) Correspondence: Wilson Sonsini Goodrich & Rosati; 650 Page Mill Road; Palo Alto; CA; 943041050 Patent Application Number: 20030158507 Date filed: June 26, 2002 Abstract: Methods of cooling blood platelet suspensions which can be stored and preserved for extended periods of time. The normal morphology of platelets and their ability to function are substantially maintained. The steps include preparing a platelet suspension having blood platelets, a carbohydrate and at least one biocompatible polymer to assist in stabilizing platelet membranes. The platelet suspension may be cooled to a temperature of less than approximately 10 degrees C. at a rate of cooling greater than 1 degree C./min. The platelet suspension may be kept at a storage temperature ranging from approximately -1 to 6 degrees C. Additionally, methods are provided for maintaining the biological activity of blood platelets. Platelet suspensions may be initially prepared which include platelets, sucrose, verapamil, magnesium chloride and a biocompatible polymer. Cooling of the platelet suspension may be followed at a cooling rate ranging from approximately 1 to 12 degrees C./min or faster to a temperature below 10 degrees C. The cooled platelet suspension may be thus stored at a storage temperatures as high as 6 degrees C. Excerpt(s): This patent application claims the benefit of the U.S. Provisional Patent Application Serial No. 60/301,320 filed on Jun. 26, 2001, which is incorporated by reference in its entirety herein. The present invention relates to methods for preserving blood platelets at refrigerator temperatures. More particularly, the invention relates to methods of cooling blood platelet suspensions which can be stored for extended periods of time while substantially maintaining the normal morphology of platelets and their ability to function. Platelets are one of the primary components of human blood. Blood is basically made up of plasma, red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Platelets are produced in the bone marrow by large cells called megakaryocytes. It is commonly understood that platelets are actually not true cells, but are fragments of membrane and cytoplasm containing granules. More specifically, platelets comprise an outer membrane and cytoplasm from megakaryocytes which in turn contain granules, dense bodies, a dense tubular system, and mitochondria. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Sustained release verapamil pharmaceutical composition free of food effect and a method for alleviating food effect in drug release Inventor(s): Seth, Pawan; (Irvine, CA) Correspondence: Harness Dickey & Pierce P L C; P O Box 828; Bloomfield Hills; MI; 48303; US Patent Application Number: 20030035834 Date filed: May 26, 2000
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Abstract: The invention provides a sustained release composition free of food effect comprising:(a) a core comprising verapamil; and(b) a functional coating comprising, based on the weight of the coating, from 30 to 80% of a gastroresistant polymer and from 10 to 40% of a hydrophilic silicon dioxide.The invention also provides a method for alleviating food effect in a verapamil pharmaceutical composition. Excerpt(s): Food effect is a well-known phenomenon that can adversely affect the pharmacokinetics of drug distribution in the body. As a result, many drugs have to be taken either in fasted or fed conditions to achieve the optimum effect. Well known examples include carbamazepine tablets (to be taken with meals), captopril tablets (to be taken one hour before meals), or azithromycin tablets (to be taken 2 hours after meal), while some other drugs remain unaffected by food, as amoxicillin for example. For this reason, FDA recommends to test bioequivalency of drug products either under fasted or fed conditions, depending on the drug. Moreover, in the latter case the meal itself is standardized. Little formulation work has been conducted to date in order to overcome this food effect disadvantage. 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 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
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Treatment of abnormal increases in gastrointestinal motility with (R)-verapamil Inventor(s): Devane, John; (Althlone, IE), Kelly, John; (Dublin, IE) Correspondence: Finnegan, Henderson, Farabow; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030092765 Date filed: September 27, 2002 Abstract: The present invention is directed to methods of treating, preventing, and/or managing abnormal increases in gastrointestinal motility, and intestinal conditions that cause the same. Such conditions include, but are not limited to, irritable bowel syndrome (IBS), infectious diseases of the small and large intestines, and symptoms of any of the foregoing. In particular, the present invention discloses methods of using (R)verapamil, as well as compositions and formulations containing the same. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/335,959, filed Nov. 15, 2001, the entire disclosure of which is incorporated herein by reference. The present invention is generally directed to methods of treating, preventing, and/or managing abnormal increases in gastrointestinal motility. Such abnormal increases may be caused by one or more intestinal conditions, including, but not limited to, irritable bowel syndrome (IBS), infectious diseases of the small and large intestine, and symptoms of any of the foregoing. In particular, the invention relates to methods of treating, preventing, and/or managing abnormal increases in gastrointestinal motility with stereo-specific forms of calcium channel blockers, including but not limited to, (R)verapamil. Irritable Bowel Syndrome (IBS) results in about 3.5 million physician visits per year, and is the most common diagnosis made by gastroenterologists, accounting for about 25% of all patients diagnosed (Camilleri and Choi, Aliment Pharmacol. Ther., 11(1):3-15, 1997). Individuals afflicted with IBS visit doctors more frequently, enjoy a lower quality of life, and miss work more often relative to those with no bowel symptoms (Drossman et al., Dig. Dis. Sci., 38:1569-1580, 1993). As a consequence, individuals suffering from IBS incur significantly higher health care costs than those without the condition (Talley et al., Gastroenterology, 109:1736-1741, 1995). 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 verapamil, 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 “verapamil” (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 verapamil. You can also use this procedure to view pending patent applications concerning verapamil. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON VERAPAMIL Overview This chapter provides bibliographic book references relating to verapamil. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on verapamil include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “verapamil” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “verapamil” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “verapamil” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Calcium antagonism in cardiovascular therapy : experience with verapamil : proceedings of the International Symposium on Calcium Antagonism in Cardiovascular Therapy, Florence, 2-4 October, 1980; ISBN: 9021994720; http://www.amazon.com/exec/obidos/ASIN/9021994720/icongroupinterna
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Calcium Channel Antagonists in Cardiovascular Disease: Focus on Verapamil by Milton Packer, William H. Frishman (Editor); ISBN: 0838510140; http://www.amazon.com/exec/obidos/ASIN/0838510140/icongroupinterna
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Cardiovascular effects of verapamil; ISBN: 0842241124; http://www.amazon.com/exec/obidos/ASIN/0842241124/icongroupinterna
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Hypertension the Next Decade: Verapamil in Focus: Proceedings of an International Symposium, Berlin by A.A. Fleckenstein (Editor); ISBN: 0443039208; http://www.amazon.com/exec/obidos/ASIN/0443039208/icongroupinterna
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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 “verapamil” (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 •
Cardiovascular effects of verapamil. Author: Randall Murray, general editor; Year: 1977
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Effort angina: studies on left ventricular pump function at rest and during exercise and the influence of nitroglycerin, propranolol, verapamil and coronary bypass surgery. Author: by Per Carlens; Year: 1979
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Verapamil: review of the First South Asian and Pacific Symposium on Calcium Antagonists in Hypertension and Cardiovascular Diseases, Manila, the Philippines, 23 February 1983: report 1983. Author: prepared and published by Excerpta Medica for Knoll AG, Pharmac; Year: 1983
Chapters on Verapamil In order to find chapters that specifically relate to verapamil, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and verapamil 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 “verapamil” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on verapamil: •
Systemic Disorders and the Periodontium Source: in Lindhe, J.; Karring, T.; Lang, N.P., eds. Clinical Periodontology and Implant Dentistry. 3rd ed. Copenhagen, Denmark: Munksgaard International Publishers Ltd. 1997. p. 332-355. Contact: Available from Munksgaard International Publishers Ltd. 35 Norre Sogade, P.O. Box 2148, DK-1016 Copenhagen K, Denmark. Phone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail:
[email protected]; http://www.munksgaard.dk. PRICE: $122.00 plus shipping and handling. ISBN: 8716120604. Summary: This chapter on systemic disorders and the periodontium is from a textbook on clinical periodontology and implant dentistry. The authors cover congenital and
10
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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hereditary disorders, viral infections, fungal infections, mucocutaneous disorders, gastrointestinal diseases, periodontal manifestations of medications, metabolic and endocrine disorders, and hematologic disorders. Specific disorders discussed include gingival enlargement, Ehlers-Danlos, epidermolysis bullosa, Papillon-Lefevre syndrome, hypophosphatasia, Chediak-Higachi disease, Down syndrome, herpetic gingivitis, herpes zoster, human papillomaviruses, human immunodeficiency virus (HIV), candidosis, recurrent oral ulcerations, lichen planus, benign bullous pemphigoid, pemphigus, erythema multiforme, lupus erythematosus, Crohns' disease, drug-induced gingival enlargements (due to dilantin, cyclosporin, nifedipin, verapamil, chemotherapy, and smoking tobacco), diabetes, pregnancy, puberty, renal insufficiency, scurvy (vitamin C deficiency), and leukemia. Full-color photographs illustrate many of the problems discussed. 41 figures. 106 references. (AA-M).
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CHAPTER 7. PERIODICALS AND NEWS ON VERAPAMIL Overview In this chapter, we suggest a number of news sources and present various periodicals that cover verapamil.
News Services and Press Releases One of the simplest ways of tracking press releases on verapamil 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 “verapamil” (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 verapamil. 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 “verapamil” (or synonyms). The following was recently listed in this archive for verapamil: •
Topical verapamil inhibits experimental diabetic cataracts Source: Reuters Industry Briefing Date: January 15, 2004
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Verapamil probably not best first-line therapy for hypertension Source: Reuters Industry Breifing Date: April 22, 2003
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Verapamil may prevent, abort sporadic hemiplegic migraine Source: Reuters Industry Breifing Date: January 24, 2003
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Verapamil improves success of second cardioversion for atrial fibrillation Source: Reuters Industry Breifing Date: August 07, 2002
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Effects of verapamil closely match normal circadian hemodynamic rhythms Source: Reuters Industry Breifing Date: February 13, 2002
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Verapamil may have benefits beyond lowering blood pressure Source: Reuters Industry Breifing Date: December 12, 2001
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Verapamil prevents cardiomyopathy in mice with limb-girdle muscular dystrophy Source: Reuters Medical News Date: January 23, 2001
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Verapamil reduces talinolol bioavailability Source: Reuters Medical News Date: March 31, 1999
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Verapamil Prevents Restenosis After Peripheral Angioplasty Source: Reuters Medical News Date: May 04, 1998
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IVAX Gets FDA Approval For Generic 120-mg Verapamil Dose Source: Reuters Medical News Date: December 18, 1997
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Wyeth-Ayerst Introduces New Dosage Of Verapamil Source: Reuters Medical News Date: May 22, 1996
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Mylan Labs Gets FDA OK On Verapamil ER Source: Reuters Medical News Date: March 26, 1996
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New Timed-Release Verapamil Formulation Follows Circadian Rhythm Of BP Variability Source: Reuters Medical News Date: August 17, 1995
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New Verapamil Formulation Allows Administration Of Higher Doses Source: Reuters Medical News Date: June 08, 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 “verapamil” (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 “verapamil” (or synonyms). If you know the name of a company that is relevant to verapamil, 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 “verapamil” (or synonyms).
Academic Periodicals covering Verapamil Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to verapamil. In addition to these sources, you can search for articles covering verapamil 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 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for verapamil. 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 verapamil. 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 verapamil: 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
Calcium Supplements •
Systemic - U.S. Brands: Alka-Mints; Amitone; Calcarb 600; Calci-Chew; Calciday 667; Calcilac; Calci-Mix; Calcionate; Calcium 600; Calglycine; Calphosan; CalPlus; Caltrate 600; Caltrate Jr; Chooz; Citracal; Citracal Liquitabs; Dicarbosil; Gencalc 600; Liquid Cal-600 http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202108.html
Trandolapril and Verapamil •
Systemic - U.S. Brands: Tarka http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203641.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.
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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
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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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
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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/
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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
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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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
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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 “verapamil” (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 21598 47 899 16 81 22641
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 “verapamil” (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 verapamil 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 verapamil. 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 verapamil. 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 “verapamil”:
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Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Migraine http://www.nlm.nih.gov/medlineplus/migraine.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 verapamil. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: 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 verapamil. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with verapamil. 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 verapamil. 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 “verapamil” (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 “verapamil”. 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 “verapamil” (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 “verapamil” (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
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
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
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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
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
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
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
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/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
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
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
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
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
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
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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
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
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/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
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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VERAPAMIL 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] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetonitriles: Compounds in which a methyl group is attached to the cyano moiety. [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] Acuity: Clarity or clearness, especially of the vision. [EU] 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] Acyl: Chemical signal used by bacteria to communicate. [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
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of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [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] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenolytic: Inhibiting the action of adrenergic nerves; inhibiting the response to epinephrine. [EU] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [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] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element,
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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] Afterload: The tension produced by the heart muscle after contraction. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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] Alginates: Salts of alginic acid that are extracted from marine kelp and used to make dental impressions and as absorbent material for surgical dressings. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH]
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Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] 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] Alternans: Ipsilateral abducens palsy and facial paralysis and contralateral hemiplegia of the limbs, due to a nuclear or infranuclear lesion in the pons. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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
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channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Amodiaquine: A 4-aminoquinoquinoline compound with anti-inflammatory properties. [NIH]
Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anal 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] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] 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] 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]
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Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] 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]
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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] Antispasmodics: Medicines that help reduce or stop muscle spasms in the intestines. Examples are dicyclomine (dy-SY-klo-meen) (Bentyl) and atropine (AH-tro-peen) (Donnatal). [NIH] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [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] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [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] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] 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]
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ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects
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bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] 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] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [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] 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
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fats in the duodenum. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] 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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [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 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,
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in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] 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] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] 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] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [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] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH]
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Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Spasm: Spasmodic contraction of the smooth muscle of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Butaclamol: A benzocycloheptapyridoisoquinolinol that has been used as an antipsychotic, especially in schizophrenia. [NIH] Buthionine sulfoximine: A drug that may help prevent resistance to some anticancer drugs. [NIH]
Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [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] 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] Calcium channel 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] 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,
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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] 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] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often
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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] Cardiotoxicity: Toxicity that affects the heart. [NIH] 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] Cardioversion: Electrical reversion of cardiac arrhythmias to normal sinus rhythm, formerly using alternatic current, but now employing direct current. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] 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] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] 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] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are
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made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell 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 motility: The ability of a cell to move. [NIH] 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Central retinal artery: The blood vessel that carries blood into eye; supplies nutrition to the retina. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [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]
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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] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] 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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Choriocapillaris: A layer of the choroid between the lamina vitrea and Sattler's layer, consisting of a network of capillaries which supplies the outer 5 layers of the retina; the network is densest at the macula. [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 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] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal
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portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Cinchona: A genus of rubiaceous South American trees that yields the toxic cinchona alkaloids from their bark; quinine, quinidine, chinconine, cinchonidine and others are used to treat malaria and cardiac arrhythmias. [NIH] Cinnarizine: A piperazine derivative with histamine H1-receptor and calcium-channel blocking activity and considerable antiemetic properties. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Claudication: Limping or lameness. [EU] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [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] 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] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains
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knowledge. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments 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]
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Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Cone cells: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [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] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of
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this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] 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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary 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 Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU]
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Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanides: Inorganic salts of hydrogen cyanide containing the -CN radical. The concept also includes isocyanides. It is distinguished from nitriles, which denotes organic compounds containing the -CN radical. [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] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with
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Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dacarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermal: Pertaining to or coming from the skin. [NIH]
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Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] 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] Dextrorotatory: Turning towards the right hand. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [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] Dicumarol: An oral anticoagulant that interferes with the metabolism of vitamin K. It is also used in biochemical experiments as an inhibitor of reductases. [NIH] 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] 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]
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Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dilantin: A drug that is often used to control seizures. [NIH] Dilatation: The act of dilating. [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] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] 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] Diuretic: A drug that increases the production of urine. [NIH] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors.
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[NIH]
Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [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] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU]
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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH]
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Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [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] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-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 Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [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]
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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [NIH] Epidermolysis Bullosa Dystrophica: Form of epidermolysis bullosa characterized by atrophy of blistered areas, severe scarring, and nail changes. It is most often present at birth or in early infancy and occurs in both autosomal dominant and recessive forms. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] 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] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Multiforme: A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic "bull's-eye" lesions usually occurring on the dorsal aspect of the hands and forearms. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks
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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] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [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] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH]
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Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] 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] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fendiline: Coronary vasodilator; inhibits calcium function in muscle cells in excitationcontraction coupling; proposed as antiarrhythmic and antianginal agents. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of
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other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Filarioidea: A superfamily of nematodes of the suborder Spirurina. Its organisms possess a filiform body and a mouth surrounded by papillae. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [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] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [NIH] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH] Flexor: Muscles which flex a joint. [NIH] Flunarizine: Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy. [NIH] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Flutter: A rapid vibration or pulsation. [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] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has
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calories. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is
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referred to as periodontitis. Called also oulitis and ulitis. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
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] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] 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] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] Gout:
Hereditary
metabolic
disorder
characterized
by
recurrent
acute
arthritis,
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hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] 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] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH]
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Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH]
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Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [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] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [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] Host: Any animal that receives a transplanted graft. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [NIH] Hydrofluoric Acid: A solution of hydrogen fluoride in water. It is a colorless fuming liquid which can cause painful burns. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H,
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atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] 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] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [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] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] 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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Illusion: A false interpretation of a genuine percept. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH]
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Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease.
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[EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] 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] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Inducers: Agents that promote the production and release of interferons. They
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include mitogens, lipopolysaccharides, and the synthetic polymers Poly A-U and Poly I-C. Viruses, bacteria, and protozoa have been also known to induce interferons. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intermittent Claudication: A symptom complex characterized by leg pain and weakness brought on by walking, with the disappearance of the symptoms following a brief rest. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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
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positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] 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] Isopropyl: A gene mutation inducer. [NIH] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] 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] Ivermectin: A mixture of ivermectin component B1a (RN 71827-03-7) and B1b (RN 70209-813), which is a semisynthetic product from Streptomyces avermitilis. A potent macrocyclic lactone disaccharide antiparasitic agent used to prevent and treat parasite infestations in animals. The compound has activity against internal and external parasites and has been found effective against arthropods, insects, nematodes, filarioidea, platyhelminths, and protozoa. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [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]
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Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetic: Pertaining to or producing motion. [EU] 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] Laryngoscopy: Examination, therapy, or surgery of the interior of the larynx performed with a specially designed endoscope. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by
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oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lichen Planus: An inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. It is characterized by distinctive purplish, flattopped papules having a predilection for the trunk and flexor surfaces. The lesions may be discrete or coalesce to form plaques. Histologically, there is a "saw-tooth" pattern of epidermal hyperplasia and vacuolar alteration of the basal layer of the epidermis along with an intense upper dermal inflammatory infiltrate composed predominantly of T-cells. Etiology is unknown. [NIH] 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] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Liquid Ventilation: Artificial respiration using an oxygenated fluid. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lisuride: An ergot derivative that acts as an agonist at dopamine D2 receptors, may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors. It has been used in parkinsonism but it may be hepatotoxic. It is commonly used as a research tool. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or
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animal to another. [NIH] Localized: Cancer which has not metastasized yet. [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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysophospholipids: Derivatives of phosphatidic acids that lack one of its fatty acyl chains due to its hydrolytic removal. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Magnesium Chloride: Magnesium chloride. An inorganic compound consisting of one magnesium and two chloride ions. The compound is used in medicine as a source of magnesium ions, which are essential for many cellular activities. It has also been used as a cathartic and in alloys. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with
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acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] 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] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Mefloquine: A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against Plasmodium falciparum with very few side effects. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] 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] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH]
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Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Menopause: Permanent cessation of 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] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] 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] 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] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] 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] 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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH]
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Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] 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] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin
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filaments slide inward among the myosin filaments. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [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 known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude,
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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] 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] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] 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] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the
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bladder. [NIH] Neurogenic Inflammation: Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [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] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] 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] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] 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
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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] 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] 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] Nitriles: Organic compounds containing the -CN radical. The concept is distinguished from cyanides, which denotes inorganic salts of hydrogen cyanide. [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] Nitroprusside: (OC-6-22)-Pentakis(cyano-C)nitrosoferrate(2-). A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All
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nociceptors are free nerve endings. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [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] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator
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gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmic Artery: Artery originating from the internal carotid artery and distributing to the eye, orbit and adjacent facial structures. [NIH] Ophthalmoscope: A lighted instrument used to examine the inside of the eye, including the retina and the optic nerve. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [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] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH]
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Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] 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]
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Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] 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] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [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] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] 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] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous
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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 Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [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] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer
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phenotype, characteristic of yeasts. [NIH] Phenoxybenzamine: An alpha-adrenergic anatagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH]
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Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [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] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous
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membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] 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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [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] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potassium Chloride: Potassium chloride. A white crystal or crystalline powder used as an electrolyte replenisher, in the treatment of hypokalemia, in buffer solutions, and in fertilizers and explosives. [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] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] Precursor: Something that precedes. In biological processes, a substance from which
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another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Propanolol: Beta blocker. [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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU]
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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] 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] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein 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]
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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 Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU]
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Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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, 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] Pulsation: A throb or rhythmical beat, as of the heart. [EU] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyran Copolymer: 2,5-Furandione polymer with 1,1'-oxybis(ethene). Copolymer of divinyl ether and maleic anhydride that is acts as an immunostimulant with antineoplastic and antiinfective properties. It is used also in combination with other antineoplastic agents. [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] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not
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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] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radius: The lateral bone of the forearm. [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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [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 failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [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]
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Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [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] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [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] Retinal Artery: Central retinal artery and its branches. It arises from the ophthalmic artery, pierces the optic nerve and runs through its center, enters the eye through the porus opticus and branches to supply the retina. [NIH] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH]
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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] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhythmicity: Regular periodicity. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rifamycins: A group of antibiotics characterized by a chromophoric naphthohydroquinone group spanned by an aliphatic bridge not previously found in other known antibiotics. They have been isolated from fermentation broths of Streptomyces mediterranei. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [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]
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Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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] Scurvy: A deficiency disease due to lack of vitamin C in the diet. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [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] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [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] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis,
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and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [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]
Sick Sinus Syndrome: Dysfunction of the sinoatrial node manifested by persistent sinus bradycardia, sinus arrest, sinoatrial exit block, chronic atrial fibrillation and inability of the heart to resume sinus rhythm following cardioversion for atrial fibrillation. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major
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component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [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] Sinoatrial Node: The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava and right atrium. Contraction impulses probably start in this node, spread over the atrium and are then transmitted by the atrioventricular bundle to the ventricle. [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] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important
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physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [NIH] 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] Spasmodic: Of the nature of a spasm. [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] 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 Capacitation: The process by which a spermatozoon becomes capable of fertilizing an ovum after it reaches the ampullary portion of the uterine tube. [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]
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Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Stabilization: The creation of a stable state. [EU] 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] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stifle: In horses, cattle, and other quadrupeds, the joint between the femur and the tibia, corresponding to the human knee. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] 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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU]
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Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] 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]
Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfadiazine: A short-acting sulfonamide used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] 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] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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]
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Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [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] 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] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Temazepam: A benzodiazepinone that acts as a GABA modulator and anti-anxiety agent. [NIH]
Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] 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] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug
Dictionary 223
is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [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]
Timolol Maleate: Antihistaminic drug. [NIH]
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Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolazoline: A vasodilator that apparently has direct actions on blood vessels and also increases cardiac output. Tolazoline can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. It is used in treatment of persistent pulmonary hypertension of the newborn. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Torticollis: Wryneck; a contracted state of the cervical muscles, producing twisting of the neck and an unnatural position of the head. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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]
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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] Trifluoperazine: A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [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] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond
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to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] 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] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] 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] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [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
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body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [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] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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
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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] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
229
INDEX A Abdomen, 149, 159, 160, 177, 189, 192, 205, 219, 220 Abdominal, 149, 158, 172, 186, 190, 203, 205 Abdominal Pain, 149, 190 Abducens, 149, 152 Ablation, 62, 149 Acantholysis, 149, 204 Acceptor, 149, 192, 203 Acetone, 102, 149, 190 Acetonitriles, 100, 149 Acetylcholine, 88, 149, 165, 199, 200 Actin, 97, 149, 196, 198 Acuity, 105, 149 Acute lymphoblastic leukemia, 76, 149 Acute lymphocytic leukemia, 149 Acute renal, 21, 37, 62, 74, 149, 184 Acute tubular, 92, 149 Acyl, 149, 193 Adaptation, 149, 165, 196 Adenine, 150, 212 Adenocarcinoma, 77, 150, 201 Adenosine, 20, 57, 58, 67, 91, 94, 150, 152, 157, 161, 206, 223 Adenosine Diphosphate, 94, 150 Adenosine Triphosphate, 58, 67, 150, 157, 206 Adenylate Cyclase, 150, 180 Adjunctive Therapy, 109, 150 Adjuvant, 90, 98, 150, 180, 181 Adrenal Cortex, 150, 151, 214 Adrenal Glands, 150, 153 Adrenal Medulla, 150, 163, 176, 177, 201 Adrenaline, 94, 150 Adrenergic, 5, 106, 109 Adrenolytic, 91, 98, 150 Adsorptive, 27, 150 Adverse Effect, 150, 206, 217 Aerobic, 36, 150, 195 Aerobic Exercise, 36, 150 Aerosol, 110, 150, 221 Afferent, 88, 150, 206 Affinity, 6, 150, 151, 156, 172, 192, 218 Afterload, 109, 151 Agar, 151, 207 Age of Onset, 151, 225 Agonist, 10, 106, 151, 158, 161, 174, 192
Albumin, 151, 195, 207 Aldosterone, 110, 111, 151 Alginates, 84, 103, 151 Algorithms, 151, 159 Alimentary, 151, 204 Alkaline, 151, 161, 205, 222 Alkaloid, 151, 157, 167, 196, 203, 212, 215, 222 Alkylating Agents, 151, 171 Alleles, 7, 151 Allergen, 152, 172 Allogeneic, 39, 152 Allograft, 91, 152 Allopurinol, 91, 152 Alopecia, 152, 170 Alpha Particles, 152, 213 Alpha-1, 152, 170, 208 Alprenolol, 152, 195 Alternans, 63, 152 Alternative medicine, 71, 80, 123, 152 Alveoli, 152, 226 Amantadine, 97, 152 Amine, 152, 185 Amino Acid Sequence, 152, 154 Amino Acids, 152, 178, 199, 204, 208, 211, 224 Amiodarone, 44, 152 Amlodipine, 12, 20, 26, 29, 43, 59, 109, 115, 152 Amodiaquine, 17, 46, 153 Amoxicillin, 104, 115, 153 Ampicillin, 153 Amyloidosis, 43, 153 Anaesthesia, 33, 49, 53, 75, 153, 187 Anal, 115, 153 Anal Fissure, 115, 153 Analgesic, 153, 166, 192, 196, 202, 212, 224 Analog, 27, 97, 153, 172, 180, 181, 201 Anatomical, 95, 153, 157, 165, 173, 187, 216 Anemia, 153, 161, 180, 193, 196 Anesthesia, 23, 34, 42, 46, 76, 153, 176, 209 Anesthetics, 153, 177 Aneurysm, 153, 226 Angina, 20, 22, 23, 28, 34, 45, 53, 61, 91, 96, 107, 109, 118, 153, 154, 190, 195, 199, 200, 204, 210 Angina Pectoris, 22, 23, 34, 45, 91, 96, 107, 109, 153, 190, 195, 210
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Verapamil
Anginal, 152, 153, 154, 158, 200 Angiography, 25, 41, 153 Angioplasty, 41, 74, 122, 153, 197 Anions, 151, 153, 190 Anorectal, 115, 153 Antagonism, 117, 154, 161, 173, 223 Anterior chamber, 154, 190 Anthracycline, 77, 154, 171, 186 Antianginal, 152, 154, 179 Antiarrhythmic, 60, 62, 109, 152, 154, 179, 192, 223 Antibacterial, 154, 219 Antibiotic, 153, 154, 157, 160, 171, 174, 178, 186, 204, 219 Antibodies, 58, 154, 183, 185, 187, 207 Antibody, 151, 154, 167, 170, 183, 185, 187, 194, 219 Anticoagulant, 154, 172, 211, 227 Anticonvulsant, 154, 162, 206, 226 Antidepressant, 154, 226 Antiemetic, 154, 155, 165, 166, 174, 225 Antigen, 151, 154, 167, 185, 186, 187, 194 Antihypertensive, 9, 20, 152, 154, 158, 180, 199, 200, 223 Anti-infective, 154, 212 Anti-inflammatory, 51, 153, 154, 156, 172, 182, 209 Anti-Inflammatory Agents, 154, 156 Antimetabolite, 154, 180 Antineoplastic, 151, 154, 170, 174, 180, 181, 196, 199, 203, 205, 208, 212, 227 Antineoplastic Agents, 151, 154, 199, 205, 212, 227 Antioxidant, 154, 203, 218 Antipsychotic, 155, 161, 165, 199, 225 Antipyretic, 155, 212 Antiseptic, 149, 155 Antispasmodics, 25, 155 Antitussive, 155, 172, 202 Antiviral, 97, 152, 155, 189 Antiviral Agents, 97, 155 Anuria, 155, 191 Anus, 153, 155, 160, 167, 207 Anxiety, 155, 210, 222 Anxiolytic, 155, 161 Aorta, 155, 163, 169, 186, 227 Apathy, 155, 199 Apoptosis, 38, 155 Aqueous, 106, 155, 158, 166, 171, 176, 191 Aqueous humor, 106, 155, 166 Arachidonic Acid, 95, 156, 191, 210 Arginine, 156, 200
Arrhythmia, 138, 154, 156, 158, 180, 227 Arterial, 40, 51, 63, 94, 95, 96, 107, 156, 160, 162, 186, 200, 211, 222 Arteries, 107, 109, 155, 156, 159, 160, 169, 186, 195, 197, 200, 212, 223 Arteriolar, 37, 156, 160, 179, 214 Arterioles, 156, 160, 162, 197, 200, 226 Arteriolosclerosis, 156 Arteriosclerosis, 93, 156 Arteriosus, 156, 212 Artery, 5, 17, 18, 46, 56, 57, 93, 94, 153, 156, 160, 169, 175, 176, 179, 197, 202, 212, 214 Ascites, 17, 111, 156, 201 Aspartate, 156, 172 Aspirin, 95, 156 Assay, 55, 72, 93, 156 Astrocytes, 156, 196 Astrocytoma, 156, 182 Asymptomatic, 4, 156, 180 Atenolol, 10, 20, 24, 33, 91, 98, 156 ATP, 11, 150, 157, 173, 181, 205, 206, 211 Atrial, 109, 122 Atrial Fibrillation, 21, 24, 26, 27, 29, 30, 31, 32, 40, 44, 47, 48, 53, 54, 62, 63, 122, 157, 217, 228 Atrial Flutter, 38, 109, 157 Atrioventricular, 26, 62, 89, 157, 218, 221 Atrioventricular Node, 157, 221 Atrium, 157, 163, 218, 221, 226 Atrophy, 149, 157, 177 Atropine, 155, 157 Attenuated, 75, 157 Attenuation, 21, 25, 157 Auditory, 75, 157 Autonomic, 149, 155, 157, 201, 204, 221 Autonomic Nervous System, 157, 205, 221 Autopsy, 20, 157 Axons, 157, 202, 214 Azithromycin, 104, 115, 157 B Babesiosis, 157, 212 Bacteria, 149, 154, 157, 158, 175, 176, 179, 189, 195, 219, 224, 226 Bactericidal, 157, 178 Bacteriophage, 157, 207, 224 Bacteriostatic, 158, 178 Bacterium, 158, 184 Basal Ganglia, 155, 158, 160, 181, 182 Base, 58, 67, 102, 150, 158, 171, 190, 191, 205, 222 Basement Membrane, 158, 178 Basophils, 158, 183, 191
231
Benign, 95, 98, 115, 119, 156, 158, 181, 183, 198, 228 Benign prostatic hyperplasia, 95, 158 Benign tumor, 98, 158 Benzene, 158, 181 Benzodiazepines, 158, 161 Bepridil, 22, 115, 158 Beta blocker, 16, 158, 209 Bethanechol, 115, 158 Bile, 158, 184, 190, 192, 220 Binding Sites, 6, 159 Bioavailability, 12, 19, 22, 50, 60, 71, 85, 86, 98, 107, 111, 113, 122, 159 Biochemical, 5, 7, 58, 77, 151, 154, 159, 172, 191, 216 Biological response modifier, 159, 188 Biological Transport, 159, 172 Biopsy, 159, 204 Biosynthesis, 156, 159, 180, 193, 210, 218 Biotechnology, 16, 18, 118, 123, 133, 159 Biotin, 59, 67, 159 Biotransformation, 159, 205 Bipolar Disorder, 109, 159 Bladder, 95, 158, 159, 170, 181, 198, 210, 225 Blastocyst, 159, 168, 206 Blister, 159, 204 Bloating, 159, 190 Blood Coagulation, 159, 161, 223 Blood Platelets, 114, 159, 194, 216 Blood pressure, 71, 73, 74, 84, 98, 101, 122 Blood-Brain Barrier, 14, 160 Body Fluids, 160, 161, 218 Bolus, 115, 160 Bolus infusion, 160 Bone Marrow, 114, 149, 158, 160, 170, 193, 194, 196, 197, 218 Bone Marrow Cells, 160, 194 Bowel, 116, 153, 160, 189, 191, 201, 220 Bowel Movement, 160, 220 Brachial, 23, 160, 213 Brachial Artery, 160, 213 Bradycardia, 58, 160, 217 Bradykinin, 88, 160, 190, 200, 207 Brain Hypoxia, 160 Brain Infarction, 160 Brain Ischemia, 94, 160 Branch, 42, 145, 160, 175, 193, 204, 205, 219, 223 Breakdown, 85, 160, 172, 181, 202, 218 Broad-spectrum, 153, 160 Bronchi, 160, 161, 177, 222
Bronchial, 158, 161, 185, 223 Bronchial Spasm, 158, 161 Buccal, 53, 161, 193 Bullous, 119, 161 Bupivacaine, 161, 192 Buspirone, 32, 161 Butaclamol, 7, 161 Buthionine sulfoximine, 92, 161 Bypass, 25, 118, 161, 197 C Cadmium, 67, 161 Cadmium Poisoning, 161 Caffeine, 161, 212 Calcification, 156, 161 Calcium blocker, 96, 161 Calcium channel blocker, 5, 7, 10, 87, 89, 92, 94, 95, 97, 98, 109, 110, 111, 115, 116 Calcium Channel Blockers, 89, 92, 94, 95, 97, 111, 115, 116, 161, 200 Calcium Channels, 4, 6, 7, 10, 162, 195, 203 Calmodulin, 158, 162, 180 Candidosis, 119, 162 Capillary, 55, 66, 160, 162, 182, 227 Capillary Permeability, 160, 162 Capsules, 22, 89, 162, 174, 180, 181, 182 Captopril, 32, 40, 104, 115, 162 Carbamazepine, 66, 104, 115, 162 Carbohydrate, 114, 162, 182, 208 Carbon Dioxide, 162, 171, 181, 206, 214 Carcinoma, 17, 18, 36, 42, 49, 57, 66, 71, 77, 162, 201, 220 Cardiac arrest, 49, 75, 162, 221 Cardiac Output, 162, 224 Cardiogenic, 24, 50, 162 Cardiomyopathy, 4, 17, 109, 111, 122, 138, 162 Cardiopulmonary, 33, 58, 163 Cardiopulmonary Bypass, 33, 58, 163 Cardiorespiratory, 150, 163 Cardioselective, 156, 163, 210 Cardiotoxicity, 33, 163 Cardiovascular, 4, 16, 73, 85, 99, 107, 111, 117, 118 Cardiovascular Abnormalities, 4, 163 Cardiovascular disease, 111, 163 Cardiovascular System, 4, 163, 172 Cardioversion, 24, 26, 30, 31, 32, 62, 122, 163, 217 Carnitine, 52, 66, 163 Carotene, 163, 214 Carrier Proteins, 163, 207 Case report, 24, 48, 57, 58, 163, 166
232
Verapamil
Cataracts, 121, 163 Catecholamine, 30, 163, 174 Catheterization, 41, 153, 163, 189, 197 Cations, 163, 190 Caudal, 163, 208 Cecum, 163, 191 Cell Cycle, 73, 164, 178, 211 Cell Death, 155, 164, 178, 198 Cell Differentiation, 164, 217 Cell Division, 157, 164, 178, 194, 196, 207, 209 Cell membrane, 159, 161, 162, 163, 164, 171, 178, 208, 218, 227 Cell motility, 39, 164 Cell proliferation, 108, 156, 164, 189, 217 Cell Respiration, 164, 195, 214 Cellobiose, 164 Cellulose, 103, 164, 195, 207 Central Nervous System Infections, 164, 183, 185 Central retinal artery, 107, 164, 214 Cerebral, 41, 93, 158, 160, 164, 169, 177, 179, 180, 182, 184, 185, 194, 203, 211, 219 Cerebral hemispheres, 158, 160, 164, 182 Cerebrovascular, 46, 93, 161, 163, 164, 200 Cerebrum, 164 Cervical, 92, 164, 184, 224 Cervix, 164, 165 Character, 153, 165, 171 Chemical Warfare, 165, 171 Chemical Warfare Agents, 165, 171 Chemokines, 5, 165 Chemotherapy, 13, 46, 53, 73, 86, 92, 93, 104, 119, 165 Chin, 165, 195 Chloroquine, 6, 14, 17, 39, 46, 165 Chlorpromazine, 111, 165, 225 Cholesterol, 158, 165, 169, 193, 218, 220 Cholinergic, 106, 115, 155, 165, 224 Choriocapillaris, 107, 165 Choroid, 107, 165, 169, 214 Chromatin, 155, 165, 177, 199, 219 Chronic, 9, 13, 89, 107, 109, 115 Chronic Disease, 9, 165, 191 Chronic renal, 44, 165, 181 Cicatrix, 165, 190 Ciliary, 106, 155, 156, 165, 166, 217 Ciliary Body, 106, 156, 165, 166, 217 Ciliary processes, 155, 166 Cinchona, 166, 212 Cinnarizine, 109, 166 Circadian, 25, 30, 73, 74, 122, 166
Cirrhosis, 42, 96, 111, 166 CIS, 166, 214 Clamp, 5, 9, 166 Claudication, 93, 166 Clear cell carcinoma, 166, 172 Clinical Medicine, 166, 209 Clinical study, 166, 169 Clinical trial, 4, 7, 133, 166, 169, 170, 196, 211, 213 Cloning, 159, 166 Coagulation, 95, 159, 166, 207, 223, 227 Cod Liver Oil, 166, 176 Codeine, 166, 172, 202 Coenzyme, 166, 193, 199, 218 Cofactor, 166, 211, 223 Cognition, 16, 166, 199 Colchicine, 77, 113, 167 Colitis, 61, 62, 167, 190 Collagen, 94, 108, 158, 167, 180, 181, 190, 207, 209 Collapse, 160, 167 Colloidal, 151, 167, 175, 205, 221 Colon, 18, 38, 49, 66, 71, 77, 112, 113, 167, 190, 191, 217 Colorectal, 36, 167 Combination Therapy, 23, 35, 110, 111, 167 Complement, 167, 168, 207 Complementary and alternative medicine, 71, 80, 167 Complementary medicine, 71, 168 Computational Biology, 133, 168 Conception, 92, 168, 179, 220 Concomitant, 40, 89, 168 Conduction, 4, 89, 157, 168 Cone, 107, 168, 221 Cone cells, 107, 168 Confusion, 168, 199, 225 Congenita, 168, 212 Congestion, 111, 155, 168, 177 Congestive heart failure, 30, 110, 111, 168, 192 Conjugated, 59, 67, 168, 170 Connective Tissue, 87, 106, 108, 160, 167, 168, 172, 181, 190, 193, 215, 222 Connective Tissue Cells, 168 Consciousness, 153, 168, 173, 214 Consolidation, 95, 168 Constipation, 104, 115, 155, 168, 190 Constriction, 168, 190, 226 Consumption, 4, 168, 214 Contraception, 92, 168
233
Contractility, 4, 10, 109, 168 Contraindications, ii, 168 Contralateral, 152, 168, 195, 202 Contrast Sensitivity, 105, 168 Controlled clinical trial, 22, 169 Controlled study, 19, 169 Conus, 169, 212 Conventional therapy, 91, 95, 169 Conventional treatment, 169 Convulsions, 154, 169, 175 Cornea, 106, 154, 155, 169, 216, 220, 228 Coronary Arteriosclerosis, 169, 197 Coronary Artery Bypass, 44, 169 Coronary Circulation, 153, 169, 200 Coronary Disease, 100, 169 Coronary heart disease, 84, 163, 169 Coronary Thrombosis, 169, 195, 197 Coronary Vessels, 169 Corpus, 57, 169, 204 Cortex, 169, 179, 180 Cortical, 111, 169, 216 Cortisone, 169, 172, 209 Cranial, 169, 170, 183, 201, 202, 205 Craniocerebral Trauma, 170, 183, 185 Cryptosporidiosis, 157, 170 Crystallization, 102, 170 Cultured cells, 67, 76, 170 Curative, 170, 223 Cutaneous, 170, 193, 226 Cyanides, 170, 200 Cyclic, 95, 97, 150, 161, 162, 170, 180, 183, 200, 206, 210, 216, 223 Cyclodextrins, 66, 170 Cyclophosphamide, 73, 170 Cyclosporine, 19, 41, 58, 91, 108, 170 Cysteine, 165, 170, 176 Cystitis, 95, 170 Cytochrome, 54, 170 Cytokines, 165, 170, 187 Cytomegalovirus, 97, 170 Cytoplasm, 114, 155, 158, 164, 171, 177, 183, 196, 199, 215, 222, 226 Cytotoxic, 11, 76, 93, 112, 171, 187, 217 Cytotoxicity, 18, 47, 66, 71, 75, 76, 171 D Dacarbazine, 31, 171 Databases, Bibliographic, 133, 171 Daunorubicin, 17, 35, 47, 76, 171, 174 Decarboxylation, 171, 185 Decidua, 171, 206 Decontamination, 36, 171 Degenerative, 169, 171, 184
Deletion, 155, 171 Delivery of Health Care, 171, 183 Dendrites, 171, 199 Deoxyribonucleic, 7, 171 Deoxyribonucleic acid, 7, 171 Deoxyribonucleotides, 171, 181 Depolarization, 171, 217 Depressive Disorder, 171, 192 Dermal, 108, 171, 192 Dermis, 109, 172, 190, 221, 224 DES, 172 Desensitization, 5, 172 Dexamethasone, 60, 73, 172 Dextromethorphan, 40, 172 Dextrorotatory, 84, 172 Diabetes Insipidus, 172, 185 Diabetes Mellitus, 172, 184, 201 Diagnostic procedure, 83, 94, 123, 172 Dialyzer, 172, 184 Diaphragm, 7, 172, 185, 207 Diarrhea, 62, 170, 172, 190 Diastole, 172 Diastolic, 27, 28, 30, 32, 36, 38, 43, 47, 52, 58, 172, 186 Dicumarol, 95, 172 Dicyclomine, 155, 172 Diffusion, 85, 89, 159, 162, 172, 188 Digestion, 151, 158, 160, 172, 189, 192, 220 Digestive tract, 113, 172, 218, 220 Dihydropyridines, 5, 97, 173 Dilantin, 119, 173 Dilatation, 153, 173, 209, 226 Dilatation, Pathologic, 173, 226 Dilated cardiomyopathy, 31, 173 Dilation, 160, 173, 185, 226 Dilator, 173, 200 Diltiazem, 76, 85, 88, 89, 93, 95, 96, 97, 108, 109, 110, 111, 115 Dimethyl, 173, 190, 199, 200 Dipyridamole, 18, 66, 71, 95, 173 Direct, iii, 27, 61, 73, 90, 95, 97, 103, 125, 163, 166, 173, 174, 203, 205, 212, 213, 222, 224 Disinfectant, 173, 178 Disposition, 13, 28, 29, 47, 53, 54, 63, 173 Dissociation, 73, 151, 173, 189 Dissociative Disorders, 173 Distal, 4, 111, 115, 169, 173, 175, 211 Diuretic, 38, 173, 181, 185, 190, 194, 219 Diurnal, 42, 173 Dizziness, 173, 227 DNA Topoisomerase, 173, 181
234
Verapamil
Docetaxel, 113, 173 Domperidone, 7, 174 Dopamine, 7, 8, 152, 155, 165, 174, 192, 196, 199 Dorsal, 174, 177, 208 Dosage Forms, 99, 100, 103, 174 Dose-dependent, 29, 84, 174 Dosimetry, 9, 174 Doxorubicin, 29, 40, 57, 73, 76, 112, 113, 174 Drug Interactions, 47, 126, 174 Drug Resistance, 6, 11, 43, 104, 174 Drug Tolerance, 174 Dyes, 158, 174, 199, 200 Dyskinesia, 28, 155, 174 Dystrophic, 174, 177 Dystrophy, 122, 174 E Edema, 175, 181, 185, 197, 201 Effector, 149, 167, 175, 206 Efficacy, 6, 7, 13, 16, 17, 21, 32, 66, 85, 94, 96, 97, 100, 161, 175 Ejaculation, 175, 216 Elastic, 23, 108, 175, 219 Elasticity, 108, 156, 169, 175, 218 Elastin, 167, 175 Elective, 175 Electrocoagulation, 166, 175 Electroconvulsive Therapy, 42, 175 Electrode, 11, 175 Electrolyte, 32, 39, 151, 175, 191, 208, 218 Electrons, 154, 158, 175, 189, 203, 213 Electrophoresis, 66, 175 Electrophysiological, 175, 227 Emboli, 175, 228 Embolism, 175, 212, 228 Embolization, 175, 228 Embolus, 175, 187 Embryo, 97, 159, 164, 175, 187 Emulsion, 89, 176 Enalapril, 18, 55, 57, 176 Endarterectomy, 153, 176 Endemic, 176, 193, 220 Endogenous, 4, 15, 108, 174, 176, 210 Endopeptidases, 176, 210 Endorphins, 176, 199 Endoscope, 176, 191 Endothelial cell, 14, 23, 39, 63, 160, 176, 223 Endothelium, 176, 200 Endothelium-derived, 176, 200 Endotoxin, 176, 200
End-stage renal, 165, 176 Enkephalins, 176, 199 Environmental Exposure, 8, 176 Environmental Health, 132, 134, 176 Enzymatic, 161, 163, 167, 177, 185, 214 Enzyme Induction, 36, 177 Enzyme Inhibitors, 62, 177, 207 Eosinophils, 177, 183, 191 Epidemic, 177, 220 Epidermal, 177, 192, 194, 228 Epidermis, 149, 159, 172, 177, 192, 204 Epidermolysis Bullosa, 45, 119, 177 Epidermolysis Bullosa Dystrophica, 45, 177 Epigastric, 177, 203 Epinephrine, 106, 150, 174, 177, 199, 201, 225 Epithelial, 42, 56, 111, 150, 159, 165, 171, 177, 184 Epithelial Cells, 42, 111, 177, 184 Epithelium, 158, 176, 177, 190, 203, 228 Erectile, 3, 111, 112, 177, 204 Erection, 177 Ergot, 177, 192 Erythema, 119, 177 Erythema Multiforme, 119, 177 Erythrocytes, 114, 153, 157, 160, 177, 213 Erythromycin, 26, 40, 157, 178 Esophageal, 45, 178 Esophagus, 172, 178, 220 Ethanol, 4, 113, 178, 179 Ether, 17, 178, 212 Etoposide, 113, 178 Eukaryotic Cells, 178, 202 Evacuation, 168, 178, 191 Excipient, 90, 178 Excitability, 178, 212 Excitation, 4, 89, 157, 178, 179, 199 Excrete, 155, 178, 191 Exhaustion, 154, 178, 193 Exocrine, 178, 203 Exocytosis, 178, 222 Exogenous, 159, 162, 176, 178, 210, 225 Extracellular, 75, 89, 107, 108, 109, 156, 168, 178, 180, 218, 222 Extracellular Matrix, 108, 168, 178, 180 Extracellular Space, 178 Extrapyramidal, 152, 155, 174, 179 Extremity, 5, 179 F Facial, 152, 179, 202 Facial Paralysis, 152, 179
235
Family Planning, 133, 179 Fat, 156, 160, 163, 169, 175, 179, 190, 192, 215, 218 Fatigue, 7, 66, 179, 184 Fatty acids, 151, 179, 206, 210, 223 Feces, 168, 179, 220 Felodipine, 26, 41, 96, 109, 115, 179 Femoral, 20, 163, 179 Femoral Artery, 20, 163, 179 Femur, 179, 220 Fendiline, 109, 179 Fentanyl, 14, 179 Fermentation, 179, 215 Fertilizers, 179, 200, 208 Fetus, 179, 206, 209, 225 Fibrillation, 38, 107, 109, 122, 179, 217 Fibrin, 94, 159, 179, 223 Fibrinogen, 94, 179, 207, 223 Fibroblasts, 62, 108, 168, 180, 189 Filarioidea, 180, 190 Filler, 90, 180 Fissure, 115, 180 Fistula, 180, 201 Flatus, 180, 181 Flecainide, 52, 58, 180 Flexor, 180, 192 Flunarizine, 93, 109, 180 Fluorouracil, 33, 173, 180 Flush, 91, 180 Flutter, 107, 109, 180 Folate, 180 Fold, 180 Folic Acid, 111, 180 Forearm, 30, 35, 37, 160, 180, 213 Forskolin, 42, 97, 180 Fosinopril, 30, 180 Fructose, 180, 182 Fundus, 181, 202 Furosemide, 55, 57, 181 G Gallopamil, 19, 47, 84, 86, 87, 96, 101, 181 Ganglia, 107, 149, 181, 198, 205, 221 Ganglion, 181, 202, 214, 228 Gas, 35, 43, 162, 172, 180, 181, 186, 190, 200, 221, 226 Gas exchange, 181, 226 Gastric, 32, 36, 85, 90, 153, 163, 174, 181, 185 Gastric Acid, 153, 181 Gastrin, 181, 185
Gastrointestinal, 73, 85, 103, 107, 116, 119, 160, 161, 172, 174, 177, 178, 181, 192, 194, 216, 219, 220, 221 Gastrointestinal tract, 85, 103, 107, 178, 181, 192, 216, 219, 220 Gelatin, 89, 181, 182, 221 Gene, 14, 49, 118, 151, 159, 177, 181, 190, 202 Genetic transcription, 181, 209 Genetics, 10, 66, 181, 205 Genistein, 76, 181 Genotype, 10, 181, 205 Germ Cells, 181, 194, 201, 202, 219 Gestation, 181, 206 Gingivitis, 119, 181 Ginseng, 79, 182 Gland, 150, 169, 182, 193, 203, 206, 210, 216, 220, 221, 223 Glioblastoma, 67, 76, 182 Glioblastoma multiforme, 67, 76, 182 Glioma, 74, 182 Glomerular, 182, 191, 194, 200, 213 Glomerular Filtration Rate, 182, 191, 194, 200 Glucans, 170, 182 Glucocorticoid, 172, 182, 209 Glucose, 17, 67, 164, 170, 172, 182, 184, 188, 213, 219 Glucuronic Acid, 182, 184 Glutamate, 172, 182 Glutamic Acid, 180, 182, 199, 209 Glycine, 182, 199 Glycoprotein, 9, 11, 13, 14, 17, 67, 72, 73, 74, 77 Glycoside, 109, 182 Gonads, 182, 186 Gout, 167, 182 Governing Board, 183, 208 Grade, 182, 183 Graft, 54, 91, 183, 185, 187, 197 Grafting, 25, 61, 169, 183, 187 Granule, 95, 183 Granulocytes, 183, 191, 217, 228 Grasses, 180, 183 Growth, 38, 95, 154, 155, 158, 159, 164, 179, 183, 185, 186, 188, 189, 194, 198, 201, 207, 211, 216, 218, 223, 225 Guanylate Cyclase, 183, 200 H Hair follicles, 172, 183 Half-Life, 91, 183 Haptens, 151, 183
236
Verapamil
Headache, 52, 161, 183, 185 Headache Disorders, 183 Health Care Costs, 116, 183 Health Expenditures, 183 Health Status, 16, 183 Heart attack, 163, 183 Heart failure, 4, 9, 31, 44, 110, 111, 184, 201, 208 Heartbeat, 184, 221, 227 Heme, 14, 170, 184 Hemiplegia, 152, 184 Hemodialysis, 26, 172, 184, 191 Hemodynamics, 29, 48, 184 Hemoglobin, 153, 178, 184 Hemolytic, 94, 184 Hemorrhage, 170, 175, 183, 184, 197, 220 Heparin, 95, 184 Hepatic, 12, 28, 42, 85, 96, 151, 184, 192, 218 Hepatitis, 96, 184, 204 Hepatocytes, 13, 63, 184 Hepatorenal Syndrome, 53, 184 Hepatotoxic, 184, 192 Hereditary, 119, 182, 184 Heredity, 181, 185 Herpes, 119, 185 Herpes Zoster, 119, 185 Heterogeneity, 10, 151, 185 Hiccup, 165, 185 Histamine, 88, 155, 166, 180, 185, 224 Histidine, 185 Homeostasis, 8, 94, 185 Homologous, 151, 170, 185, 222 Hormone, 42, 150, 151, 169, 172, 177, 181, 185, 188, 201, 207, 209, 215, 216, 217, 218, 223 Host, 157, 162, 185, 187, 192, 225, 227 Human papillomavirus, 119, 185 Hybridomas, 185, 189 Hydrocephalus, 185, 190 Hydrochlorothiazide, 10, 23, 32, 38, 185 Hydrofluoric Acid, 185, 217 Hydrogen, 149, 152, 158, 162, 170, 173, 185, 186, 192, 196, 199, 200, 203, 211 Hydrogen Cyanide, 170, 186, 200 Hydrolysis, 11, 94, 159, 164, 186, 206, 208, 211 Hydrophilic, 11, 89, 90, 104, 115, 186 Hydroxylysine, 167, 186 Hydroxyproline, 167, 186 Hyperalgesia, 88, 186 Hyperplasia, 186, 192
Hypersensitivity, 152, 172, 186, 192, 215 Hyperthyroidism, 186, 210 Hypertrophic cardiomyopathy, 25, 38, 39, 45, 52, 56, 59, 109, 186 Hypertrophy, 57, 111, 158, 186, 208 Hypogonadism, 38, 186 Hypotension, 45, 155, 158, 169, 186 Hypotensive, 76, 86, 101, 113, 186, 190 Hypoxic, 84, 186 I Id, 47, 68, 77, 138, 144, 146, 186 Idarubicin, 35, 186 Idiopathic, 27, 31, 39, 42, 47, 58, 63, 95, 186 Iliac Artery, 179, 186 Illusion, 186, 227 Imidazole, 159, 185, 186 Immune function, 186, 187 Immune response, 150, 154, 169, 183, 187, 221, 225, 227 Immune system, 187, 192, 225, 228 Immunodeficiency, 119, 187, 221 Immunodeficiency syndrome, 187, 221 Immunoglobulins, 187, 207 Immunology, 14, 150, 151, 187 Immunosuppressant, 151, 180, 187 Immunosuppressive, 91, 113, 170, 182, 187 Immunosuppressive Agents, 113, 187 Immunotherapy, 172, 187 Impairment, 8, 62, 174, 187, 195 Implantation, 168, 187 Impotence, 41, 87, 177, 187, 203 In vitro, 7, 9, 13, 17, 20, 39, 40, 43, 48, 61, 72, 73, 76, 84, 187 In vivo, 13, 14, 29, 38, 40, 74, 88, 184, 187, 223 Incision, 187, 189 Indicative, 94, 117, 187, 204, 226 Induction, 13, 28, 101, 108, 155, 187, 209, 218 Infancy, 177, 187 Infarction, 9, 16, 44, 51, 61, 109, 111, 160, 185, 187, 214 Infection, 9 Infertility, 92, 188 Infiltration, 188, 209, 228 Inflammation, 88, 151, 154, 156, 165, 167, 170, 181, 184, 185, 188, 192, 199, 204, 210, 215, 222, 226 Infusion, 52, 57, 75, 188, 197 Ingestion, 5, 32, 36, 161, 180, 188, 195, 208, 222 Inhalation, 110, 150, 185, 188, 208
237
Initiation, 188, 209 Inlay, 188, 214 Innervation, 96, 188 Inorganic, 170, 188, 193, 196, 200 Inositol, 188, 216 Inotropic, 48, 49, 84, 156, 174, 179, 188 Insecticides, 188, 205 Insight, 7, 14, 188 Insulin, 15, 67, 188, 190, 225 Insulin-dependent diabetes mellitus, 188 Intensive Care, 49, 75, 188 Interferon, 31, 97, 188, 189, 193 Interferon Inducers, 97, 188 Interferon-alpha, 31, 188, 189 Interleukin-2, 37, 189 Interleukin-6, 62, 189 Interleukins, 187, 189 Intermittent, 93, 189 Intermittent Claudication, 93, 189 Interstitial, 95, 178, 189, 213 Intestinal, 12, 41, 85, 113, 116, 163, 170, 189 Intestine, 90, 116, 160, 189, 191, 205 Intoxication, 4, 18, 20, 50, 189, 228 Intracellular, 13, 35, 40, 45, 47, 76, 90, 91, 98, 161, 187, 189, 200, 208, 210, 216, 217 Intramuscular, 112, 189, 204 Intraocular, 105, 106, 180, 189, 201 Intraocular pressure, 105, 106, 180, 189, 201 Intravenous, 7, 17, 24, 25, 27, 33, 41, 42, 43, 48, 51, 57, 75, 112, 188, 189, 204 Intrinsic, 11, 151, 158, 189 Intubation, 49, 163, 189 Invasive, 41, 51, 54, 189 Involuntary, 179, 189, 197, 219 Ionization, 66, 189 Ionizing, 152, 176, 189 Ions, 15, 89, 97, 107, 109, 158, 162, 173, 175, 186, 189, 193, 208, 211, 215, 218 Iris, 106, 154, 156, 169, 190, 212 Irritable Bowel Syndrome, 116, 190 Ischemia, 5, 76, 86, 88, 94, 109, 157, 160, 190, 197, 214 Isopropyl, 96, 100, 190 Isosorbide, 42, 190 Isosorbide Dinitrate, 42, 190 Isradipine, 41, 48, 49, 109, 115, 190 Ivermectin, 66, 190 J Jaundice, 184, 190 Joint, 180, 190, 220, 222
K Kallidin, 160, 190 Kb, 132, 190 Keloid, 25, 62, 190 Ketone Bodies, 149, 190 Kidney Failure, 9, 176, 191, 194 Kidney Failure, Acute, 191 Kidney Failure, Chronic, 191 Kinetic, 12, 13, 14, 60, 189, 191 L Large Intestine, 116, 163, 172, 189, 191, 213, 218 Laryngoscopy, 49, 191 Larynx, 191 Lavage, 32, 36, 191 Laxative, 151, 191, 195, 219 Lectins, 92, 191 Lens, 106, 155, 163, 168, 191, 214, 227 Lesion, 94, 152, 169, 191, 222, 225 Leucocyte, 152, 191, 193 Leukaemia, 77, 191 Leukemia, 21, 28, 35, 47, 50, 59, 76, 77, 93, 119, 174, 191 Leukocytes, 13, 114, 158, 160, 165, 170, 177, 183, 189, 191, 196, 199 Leukotrienes, 156, 191 Levo, 192, 223 Levorphanol, 172, 192 Library Services, 144, 192 Lichen Planus, 119, 192 Lidocaine, 31, 110, 192 Lidoflazine, 115, 192 Ligaments, 169, 192 Lipid, 156, 162, 188, 192, 203 Lipid Peroxidation, 192, 203 Lipophilic, 85, 192 Lipopolysaccharides, 189, 192 Liquid Ventilation, 61, 192 Lisinopril, 23, 192 Lisuride, 110, 192 Lithium, 11, 43, 155, 192 Liver Cirrhosis, 184, 192 Liver Transplantation, 53, 192 Localized, 153, 160, 184, 187, 192, 193, 201, 207, 225 Lovastatin, 193, 218 Lupus, 119, 193, 222 Lymph, 164, 176, 193 Lymph node, 164, 193 Lymphatic, 85, 176, 187, 193, 201, 207, 218, 219, 223 Lymphatic system, 85, 193, 218, 219, 223
238
Verapamil
Lymphoblastic, 35, 76, 193 Lymphoblasts, 149, 193 Lymphocytic, 39, 45, 193 Lymphoid, 21, 154, 191, 193 Lymphoma, 40, 193 Lysophospholipids, 28, 193 M Macula, 165, 193 Magnesium Chloride, 114, 193 Maintenance therapy, 45, 193 Malaria, 6, 14, 166, 193, 194 Malaria, Falciparum, 193, 194 Malaria, Vivax, 193, 194 Malignant, 31, 74, 150, 154, 156, 182, 194, 196, 198 Malignant tumor, 194, 196 Mammary, 169, 194 Mania, 45, 194 Manic, 109, 155, 159, 192, 194 Mannitol, 91, 107, 194 Mechanical ventilation, 7, 194 Medial, 156, 194, 202 Mediate, 77, 174, 194 Mediator, 189, 194, 217 Medicament, 87, 90, 91, 98, 194, 221 MEDLINE, 133, 194 Medullary, 172, 194 Mefloquine, 17, 194 Megakaryocytes, 114, 160, 194 Megaloblastic, 180, 194 Meiosis, 194, 222 Melanin, 190, 194, 225 Melanocytes, 194 Melanoma, 31, 194 Membrane Glycoproteins, 195 Menopause, 195, 209, 210 Mental, iv, 4, 15, 43, 132, 134, 165, 166, 168, 173, 179, 194, 195, 211, 215, 225 Mental Disorders, 195, 211 Mental Processes, 173, 195, 211 Mesencephalic, 8, 195 Metabolite, 12, 13, 53, 159, 173, 180, 193, 195, 209 Metastasis, 77, 195, 198 Metastatic, 77, 195, 216 Methanol, 102, 195 Methylcellulose, 103, 195 Metoprolol, 20, 23, 25, 32, 34, 85, 195 MI, 9, 93, 114, 147, 195 Mibefradil, 6, 195 Microbe, 195, 224 Microorganism, 166, 195, 227
Microtubules, 195, 203 Milk Thistle, 195, 217 Mitochondria, 8, 114, 195, 197, 202 Mitochondrial Swelling, 195, 198 Mitosis, 155, 191, 196 Mitotic, 173, 178, 196, 227 Mitotic inhibitors, 173, 196 Mitoxantrone, 47, 196 Modeling, 6, 47, 196 Modification, 196, 212 Modulator, 76, 196, 222 Molecular, 5, 6, 9, 15, 35, 66, 133, 135, 159, 162, 168, 179, 184, 190, 196, 209, 224 Molecule, 154, 158, 159, 162, 166, 167, 173, 175, 176, 178, 182, 186, 196, 203, 213, 217, 226 Monitor, 16, 196, 201 Monoamine, 8, 196 Monocytes, 189, 191, 196 Monotherapy, 36, 196 Morphine, 13, 23, 166, 196, 198, 202 Morphological, 175, 194, 196 Morphology, 92, 114, 196 Motility, 92, 116, 196, 216 Mucocutaneous, 119, 196 Mucosa, 193, 196, 209 Mucus, 92, 196 Multicenter study, 45, 196 Multidrug resistance, 11, 72, 73, 74, 75, 76, 77, 86, 112 Multiple Myeloma, 43, 196 Muscle Contraction, 7, 15, 196, 215 Muscle relaxant, 197, 206, 221 Muscle Relaxation, 197, 198, 221 Muscle Spindles, 197, 206 Muscular Dystrophies, 174, 197 Mutagenesis, 6, 197 Mutagens, 197 Myelofibrosis, 94, 197 Myelogenous, 28, 197 Myocardial infarction, 9, 16, 20, 21, 41, 44, 51, 60, 61, 109, 111, 169, 195, 197, 210, 228 Myocardial Ischemia, 21, 153, 169, 197 Myocardial Reperfusion, 197, 214 Myocardial Reperfusion Injury, 197, 214 Myocardium, 17, 48, 153, 195, 197 Myoclonus, 48, 197 Myosin, 197, 198 Myotonia, 198, 212 N Narcotic, 179, 192, 196, 198, 224
239
Nausea, 154, 155, 174, 198, 225 Necrosis, 92, 94, 155, 160, 182, 187, 195, 197, 198, 214, 215, 216 Need, 3, 96, 115, 118, 139, 149, 150, 165, 198 Neoplasms, 154, 171, 185, 198 Neoplastic, 185, 193, 198 Nephron, 26, 41, 111, 198 Nephrosis, 184, 198 Nerve, 95, 105 Nerve Endings, 198, 201 Nerve Growth Factor, 95, 198 Nervous System, 4, 149, 150, 157, 158, 161, 162, 164, 181, 182, 192, 194, 196, 198, 199, 202, 204, 208, 216, 221, 222 Neural, 150, 198, 204, 218 Neurogenic, 88, 198, 199, 225 Neurogenic Inflammation, 88, 199 Neuroleptic, 28, 155, 199 Neurologic, 182, 185, 199 Neuromuscular, 149, 179, 199 Neuromuscular Junction, 149, 199 Neuronal, 94, 162, 199 Neurons, 8, 171, 181, 197, 198, 199, 221, 222 Neuropathy, 33, 199, 204 Neuropeptide, 10, 199 Neurotoxicity, 172, 199 Neurotransmitter, 10, 149, 150, 160, 174, 182, 185, 199, 201, 216, 217, 219, 221 Neutrons, 152, 199, 213 Neutrophils, 5, 183, 191, 199 Niacinamide, 199 Nicardipine, 23, 37, 49, 85, 88, 109, 113, 115, 199 Nicorandil, 58, 67, 199 Nifedipine, 5, 12, 20, 28, 48, 49, 50, 73, 85, 88, 89, 92, 93, 94, 96, 97, 108, 109, 115, 200 Nimodipine, 28, 67, 76, 88, 109, 115, 200 Nisoldipine, 109, 115, 200 Nitrates, 89, 200 Nitrendipine, 66, 115, 200 Nitric acid, 200 Nitric Oxide, 5, 20, 115, 200 Nitric-Oxide Synthase, 49, 200 Nitriles, 86, 170, 200 Nitrogen, 35, 151, 152, 170, 186, 191, 200, 225 Nitroglycerin, 25, 57, 61, 118, 190, 200 Nitroprusside, 5, 97, 200 Nociceptors, 88, 200
Non-small cell lung cancer, 53, 201 Norepinephrine, 48, 150, 174, 199, 201 Nuclear, 152, 158, 175, 178, 181, 182, 198, 201, 214 Nuclei, 152, 175, 179, 196, 199, 201, 202, 211 Nucleic acid, 197, 200, 201, 212 Nucleus, 155, 157, 158, 165, 170, 171, 177, 178, 194, 196, 199, 201, 209, 211 O Octreotide, 58, 201 Ocular, 87, 88, 105, 106, 201 Ocular Hypertension, 105, 201 Oculomotor, 195, 201 Oedema, 50, 201 Ointments, 174, 201 Oliguria, 191, 194, 201 On-line, 51, 75, 147, 201 Oocytes, 15, 201 Opacity, 163, 201 Operon, 201, 209 Ophthalmic, 105, 202, 214 Ophthalmic Artery, 202, 214 Ophthalmoscope, 202 Opium, 196, 202, 203 Opsin, 202, 214 Optic Chiasm, 202 Optic Disk, 105, 169, 202 Optic Nerve, 105, 202, 214, 216 Optic nerve head, 105, 202 Organ Transplantation, 62, 91, 202 Organelles, 35, 171, 194, 196, 202, 207 Orthostatic, 101, 155, 201, 202 Osmolarity, 194, 202 Osmosis, 202 Osmotic, 107, 151, 190, 195, 202 Outpatient, 12, 202 Ovary, 73, 182, 202, 203 Overdose, 45, 46, 48, 50, 53, 203 Ovum, 171, 181, 203, 209, 219, 228 Oxidation, 7, 8, 149, 154, 159, 170, 192, 203 Oxidative Stress, 8, 203 Oxygenator, 163, 203 P Paclitaxel, 113, 203 Palliative, 203, 223 Palsy, 152, 203, 219 Pancreas, 91, 149, 159, 188, 203, 219 Pancreatic, 67, 163, 203 Papaverine, 25, 97, 202, 203 Papillomavirus, 203 Paralysis, 179, 195, 203, 219
240
Verapamil
Parasite, 6, 14, 190, 203 Parathyroid, 50, 203, 222 Parathyroid Glands, 203 Parathyroid hormone, 50, 203 Parenteral, 85, 204 Parkinsonism, 155, 192, 204 Paroxysmal, 52, 60, 153, 183, 204 Particle, 90, 204, 219, 224 Patch, 5, 9, 108, 169, 204, 224 Pathogenesis, 94, 115, 204 Pathologic, 155, 159, 162, 169, 186, 204, 226 Pathologic Processes, 155, 204 Pathophysiology, 10, 204 Pelvic, 95, 204, 210 Pemphigus, 119, 149, 204 Penicillin, 153, 154, 204 Penis, 87, 111, 175, 204 Peptide, 11, 54, 176, 204, 207, 208, 210, 211, 223 Perception, 168, 204, 216 Percutaneous, 54, 58, 204 Perfusion, 106, 204 Perhexiline, 115, 204 Periodicity, 204, 215 Periodontitis, 182, 204 Peripheral blood, 189, 204 Peripheral Nervous System, 176, 184, 199, 203, 204, 219, 221 Peripheral Vascular Disease, 93, 180, 205 Peripheral vision, 205, 227 Peristalsis, 174, 205 Peritoneal, 156, 201, 205 Peritoneal Cavity, 156, 201, 205 Pesticides, 8, 188, 205 Petrolatum, 176, 205 P-Glycoprotein, 93, 113, 205 Pharmaceutical Preparations, 164, 178, 181, 205 Pharmaceutical Solutions, 174, 205 Pharmacodynamic, 14, 75, 205 Pharmacodynamics, 13, 29, 36, 104 Pharmacogenetics, 9, 205 Pharmacokinetic, 9, 12, 14, 75, 100, 205 Pharmacologic, 9, 29, 93, 107, 153, 183, 205, 224, 225 Phenolphthalein, 176, 205 Phenotype, 7, 14, 74, 112, 205 Phenoxybenzamine, 25, 206 Phenyl, 96, 100, 158, 206 Phenytoin, 108, 162, 206 Phosphatidic Acids, 193, 206 Phosphodiesterase, 95, 206
Phospholipases, 206, 217 Phosphorus, 35, 161, 203, 206 Phosphorylated, 11, 166, 206 Phosphorylates, 11, 206 Photocoagulation, 166, 206 Photodynamic therapy, 36, 206 Photoreceptors, 168, 206 Phototransduction, 206, 216 Physiologic, 7, 91, 107, 151, 159, 183, 198, 206, 210, 213, 225 Physiology, 5, 6, 66, 77, 150, 175, 191, 206 Pigment, 56, 194, 206 Pituitary Gland, 180, 206 Placenta, 43, 206 Plague, 87, 207 Plants, 151, 157, 162, 182, 196, 201, 207, 224 Plaque, 4, 61, 67, 87, 153, 207 Plasma, 12, 88, 91, 98, 99, 114 Plasma cells, 154, 196, 207 Plasma protein, 55, 151, 207, 211 Plastids, 202, 207 Platelet Activation, 95, 207, 217 Platelet Aggregation, 95, 180, 200, 207, 223 Platelet-Derived Growth Factor, 23, 207 Platelets, 23, 94, 114, 200, 207, 223 Platyhelminths, 190, 207 Pleural, 201, 207 Pleural cavity, 201, 207 Plexus, 23, 207 Podophyllotoxin, 178, 207 Poisoning, 61, 161, 177, 189, 198, 208 Polymerase, 155, 208, 209 Polymers, 88, 89, 103, 189, 208, 211 Polymorphic, 60, 208 Polymorphism, 10, 17, 208 Polypeptide, 152, 167, 179, 208, 209, 218, 228 Polysaccharide, 154, 164, 208 Pons, 152, 179, 208 Posterior, 106, 153, 156, 165, 174, 190, 203, 208, 216 Postherpetic Neuralgia, 152, 208 Postsynaptic, 208, 217, 222 Potassium, 17, 46, 76, 88, 151, 185, 200, 208, 212 Potassium Channels, 46, 208 Potassium Chloride, 88, 208 Potentiation, 208, 217 Practice Guidelines, 134, 208 Prazosin, 101, 208
241
Precursor, 86, 156, 170, 174, 175, 176, 177, 201, 208, 209, 211, 225 Prednisolone, 209 Prednisone, 52, 209 Premenopausal, 50, 209 Prenatal, 175, 209 Presynaptic, 198, 199, 209, 222 Prevalence, 38, 209 Probe, 59, 94, 209 Procaine, 192, 209 Prodrug, 180, 209 Progression, 95, 105, 209 Progressive, 156, 164, 165, 166, 174, 183, 191, 197, 198, 207, 209, 213 Projection, 201, 202, 209 Prolactin, 174, 209 Proline, 167, 186, 209 Promotor, 113, 209 Prone, 85, 209 Propanolol, 91, 209 Prophase, 201, 209, 222 Prophylaxis, 87, 97, 155, 180, 209, 225, 227 Proportional, 91, 98, 108, 209 Propranolol, 25, 38, 39, 40, 45, 62, 85, 98, 118, 156, 210, 223 Prostaglandin, 111, 210, 223 Prostaglandins A, 88, 210 Prostaglandins D, 210 Prostate, 158, 210 Prostate gland, 210 Prostatic Hyperplasia, 95, 210 Protease, 9, 77, 167, 210, 215 Protease Inhibitors, 9, 210 Protective Agents, 161, 210 Protein Binding, 75, 210 Protein C, 108, 151, 152, 158, 211 Protein Kinases, 11, 211 Protein S, 118, 155, 159, 178, 211 Protein-Tyrosine Kinase, 181, 211 Proteinuria, 196, 211 Proteolytic, 152, 167, 179, 211 Prothrombin, 211, 223 Protocol, 9, 211 Protons, 152, 186, 189, 211, 213 Proto-Oncogene Proteins, 203, 211 Proto-Oncogene Proteins c-mos, 203, 211 Protozoa, 189, 190, 195, 211 Proximal, 7, 173, 209, 211 Pruritic, 192, 211 Psychiatry, 13, 45, 211, 226 Psychic, 195, 211, 216 Psychology, 173, 211
Psychomotor, 162, 199, 211 Puberty, 119, 212 Public Policy, 133, 212 Publishing, 16, 212 Pulmonary, 14, 44, 46, 50, 58, 61, 159, 168, 191, 192, 212, 224, 226, 228 Pulmonary Artery, 58, 159, 212, 226 Pulmonary congestion, 44, 212 Pulmonary Edema, 46, 50, 191, 212 Pulmonary Embolism, 212, 228 Pulmonary hypertension, 212, 224 Pulsation, 180, 212 Pulse, 40, 196, 212 Pupil, 169, 173, 212 Purines, 88, 212, 228 Pyran Copolymer, 97, 212 Q Quality of Life, 5, 9, 112, 116, 212 Quaternary, 101, 212, 221 Quinidine, 37, 43, 44, 47, 166, 212 Quinine, 17, 56, 73, 101, 166, 212 R Race, 10, 12, 54, 56, 84, 86, 99, 102, 104, 212, 213 Racemic, 56, 84, 86, 99, 102, 104, 213 Radial Artery, 25, 61, 213 Radiation, 109, 153, 176, 189, 213, 218 Radioactive, 171, 183, 186, 187, 189, 201, 213 Radiological, 204, 213 Radius, 213 Randomized, 18, 19, 47, 54, 56, 175, 213 Reabsorption, 185, 213 Receptor, 9, 23, 106, 111, 150, 154, 161, 166, 168, 172, 174, 213, 217 Recombinant, 37, 213, 226 Rectum, 49, 153, 155, 160, 167, 172, 180, 181, 191, 210, 213, 217, 221 Recurrence, 4, 24, 30, 159, 204, 213 Red blood cells, 114, 177, 184, 213 Reductase, 193, 213, 218 Reentry, 27, 28, 213 Refer, 1, 161, 167, 173, 176, 185, 193, 199, 213, 224 Refraction, 213, 219 Regimen, 175, 213, 215 Relaxant, 180, 203, 206, 213, 221 Remission, 159, 193, 213 Renal failure, 74, 184, 213 Renin, 162, 213, 214 Renin-Angiotensin System, 162, 214 Reperfusion, 5, 76, 197, 214
242
Verapamil
Reperfusion Injury, 5, 76, 214 Resolving, 101, 214 Respiration, 162, 192, 196, 214 Respirator, 194, 214, 226 Respiratory Physiology, 214, 226 Restoration, 17, 111, 197, 214 Resuscitation, 58, 93, 214 Retina, 105, 106, 164, 165, 168, 169, 191, 202, 206, 214, 215, 217, 227 Retinal, 56, 107, 168, 202, 206, 214, 227 Retinal Artery, 107, 214 Retinal Ganglion Cells, 202, 214 Retinol, 214, 215 Retreatment, 54, 76, 215 Reversion, 59, 163, 215 Rhabdomyolysis, 37, 74, 215 Rheumatism, 215 Rheumatoid, 26, 165, 215 Rheumatoid arthritis, 26, 165, 215 Rhythmicity, 4, 215 Ribose, 150, 215 Rifamycins, 11, 215 Rigidity, 4, 204, 207, 215 Ritonavir, 34, 215 Rod, 107, 158, 166, 215 Rodenticides, 205, 215 Ryanodine, 9, 15, 215 S Saline, 11, 88, 215 Salivary, 170, 215 Salivary glands, 170, 215 Saphenous, 23, 39, 54, 169, 215 Saphenous Vein, 23, 39, 54, 169, 215 Sarcolemma, 10, 197, 215 Sarcoplasmic Reticulum, 15, 215 Schizoid, 215, 228 Schizophrenia, 161, 175, 215, 216, 228 Schizotypal Personality Disorder, 216, 228 Sclera, 106, 165, 169, 216 Sclerosis, 156, 216 Screening, 166, 216 Scurvy, 119, 216 Sebaceous, 172, 216 Sebaceous gland, 172, 216 Second Messenger Systems, 5, 216 Secondary tumor, 195, 216 Secretion, 41, 42, 106, 172, 185, 188, 189, 196, 201, 216 Sedentary, 16, 216 Seizures, 162, 173, 182, 204, 206, 216 Semen, 92, 175, 210, 216 Semisynthetic, 153, 178, 190, 216
Sensibility, 153, 186, 216 Sequester, 216, 222 Serotonin, 155, 161, 192, 199, 216, 225 Serrata, 165, 217 Serum, 19, 30, 55, 99, 109, 151, 153, 167, 191, 217 Sex Characteristics, 212, 217 Sharpness, 217, 227 Shock, 5, 24, 197, 217, 225 Sick Sinus Syndrome, 52, 217 Side effect, 93, 97, 104, 105, 106, 113, 125, 150, 155, 170, 194, 217, 224 Sigmoid, 49, 217 Sigmoid Colon, 49, 217 Signal Transduction, 5, 188, 217 Signs and Symptoms, 111, 213, 217 Silicon, 104, 115, 217 Silicon Dioxide, 104, 115, 217 Silymarin, 76, 195, 217 Simvastatin, 40, 218 Sinoatrial Node, 217, 218 Skeletal, 166, 196, 197, 212, 215, 218, 219, 221 Skeleton, 149, 179, 190, 210, 218 Skin Aging, 108, 218 Skull, 170, 218, 222 Small cell lung cancer, 218 Small intestine, 163, 185, 189, 218 Smallpox, 218, 226 Smooth muscle, 58, 89, 97, 107, 109, 158, 161, 168, 179, 180, 185, 190, 196, 200, 203, 214, 218, 219, 221 Social Environment, 212, 218 Sodium, 51, 86, 97, 103, 111, 151, 183, 185, 200, 206, 212, 213, 218, 221, 226 Sodium Channels, 206, 212, 218, 226 Soft tissue, 160, 218 Solid tumor, 174, 218 Solvent, 149, 158, 178, 195, 202, 205, 218 Somatostatin, 201, 218 Sorbitol, 194, 219 Sotalol, 52, 219 Sound wave, 168, 219 Spasm, 45, 91, 98, 115, 185, 195, 219, 222 Spasmodic, 32, 161, 219 Spastic, 190, 219 Specialist, 139, 173, 219 Species, 79, 152, 167, 170, 177, 193, 194, 196, 202, 203, 212, 219, 221, 225, 227 Specificity, 151, 162, 176, 219 Spectrum, 97, 219 Sperm, 92, 219
243
Sperm Capacitation, 92, 219 Spermatozoa, 216, 219 Spermatozoon, 219 Sphincter, 115, 191, 219 Spinal cord, 156, 160, 164, 165, 181, 184, 198, 199, 204, 219, 221 Spleen, 153, 170, 193, 219 Sporadic, 60, 122, 220 Squamous, 42, 201, 220 Squamous cell carcinoma, 201, 220 Stabilization, 206, 220 Steady state, 31, 66, 74, 220 Steel, 166, 220 Stent, 60, 220 Sterile, 203, 220 Sterility, 170, 188, 220 Steroid, 169, 218, 220 Stifle, 113, 220 Stimulant, 161, 185, 190, 220 Stimulus, 168, 175, 178, 188, 199, 220, 223 Stomach, 149, 172, 178, 181, 185, 191, 198, 205, 218, 219, 220 Stool, 115, 167, 190, 191, 220 Stress, 8, 26, 109, 157, 163, 190, 198, 203, 215, 220 Stria, 8, 220 Stroke, 4, 5, 9, 16, 93, 94, 132, 162, 163, 220 Stroma, 190, 220 Subacute, 187, 220 Subarachnoid, 183, 220 Subclinical, 187, 216, 221 Subcutaneous, 111, 112, 175, 201, 204, 221 Subspecies, 219, 221 Substance P, 178, 195, 216, 221 Substrate, 9, 11, 12, 13, 59, 177, 221 Succinylcholine, 76, 221 Sudden death, 39, 221 Sulfadiazine, 17, 221 Suppositories, 181, 221 Suppression, 26, 221 Supraventricular, 34, 52, 60, 63, 107, 109, 221 Suspensions, 114, 221 Sweat, 172, 221 Sweat Glands, 172, 221 Sympathetic Nervous System, 52, 157, 221 Sympathomimetic, 174, 177, 201, 221 Symptomatic, 25, 58, 59, 61, 111, 152, 180, 221, 222 Symptomatic treatment, 61, 152, 222 Synapses, 222 Synapsis, 222
Synaptic, 8, 199, 217, 222 Synaptic Vesicles, 8, 222 Systemic lupus erythematosus, 165, 222 Systemic therapy, 165, 222 Systolic, 43, 186, 222 T Tachycardia, 20, 27, 28, 31, 34, 39, 42, 44, 47, 52, 58, 60, 63, 67, 109, 222 Tardive, 28, 155, 222 Temazepam, 32, 36, 222 Temporal, 107, 183, 222 Teratogenic, 151, 173, 222 Tetany, 203, 222 Theophylline, 212, 222 Therapeutics, 19, 24, 26, 29, 30, 33, 35, 40, 41, 49, 54, 60, 72, 126, 223 Thermal, 88, 110, 173, 199, 223 Thigh, 179, 223 Thoracic, 25, 61, 172, 223 Threshold, 178, 186, 223 Thrombin, 23, 179, 207, 211, 223 Thrombocytes, 94, 114, 207, 223 Thrombomodulin, 211, 223 Thrombosis, 23, 94, 211, 220, 223 Thromboxanes, 156, 223 Thrombus, 52, 169, 187, 197, 207, 223, 226 Thymus, 193, 223 Thyroid, 186, 203, 223, 225 Thyroid Gland, 186, 203, 223 Thyroid Hormones, 223, 225 Thyrotropin, 42, 223 Thyroxine, 151, 223 Timolol, 58, 91, 98, 106, 223 Timolol Maleate, 58, 223 Tissue, 5, 7, 14, 49, 84, 86, 87, 88, 94, 106, 152, 154, 157, 158, 159, 160, 162, 163, 165, 166, 168, 170, 174, 175, 177, 179, 180, 182, 183, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 201, 204, 205, 206, 207, 214, 216, 217, 218, 220, 222, 224, 225 Tolazoline, 25, 224 Tomography, 9, 224 Tonic, 108, 224 Topical, 25, 58, 87, 88, 98, 105, 106, 108, 115, 121, 178, 205, 224 Torsion, 187, 224 Torticollis, 32, 224 Toxic, iv, 96, 99, 151, 157, 158, 166, 171, 174, 176, 183, 184, 186, 195, 199, 200, 207, 224 Toxicity, 8, 23, 26, 34, 163, 174, 186, 224
244
Verapamil
Toxicology, 15, 23, 52, 61, 134, 224 Toxin, 8, 176, 224 Toxoplasmosis, 157, 221, 224 Trace element, 217, 224 Traction, 166, 224 Tramadol, 100, 224 Transdermal, 59, 60, 98, 108, 224 Transduction, 5, 88, 217, 224 Transfection, 159, 224 Translation, 178, 224 Translocation, 178, 224 Transmitter, 149, 156, 174, 194, 201, 222, 224 Transplantation, 19, 21, 22, 28, 39, 40, 53, 62, 76, 91, 165, 191, 225 Trauma, 5, 198, 225 Tremor, 195, 204, 223, 225 Trifluoperazine, 17, 225 Tryptophan, 167, 216, 225 Tuberculosis, 168, 193, 225 Type 2 diabetes, 46, 225 Tyrosine, 174, 211, 225 U Ulcer, 115, 225 Unconscious, 153, 186, 225 Uremia, 191, 213, 225 Ureters, 225 Urethra, 158, 204, 210, 225 Uric, 152, 183, 212, 225 Urinary, 95, 158, 170, 172, 185, 201, 208, 225, 228 Urinary Retention, 158, 208, 225 Urinary tract, 95, 172, 225 Urine, 27, 63, 95, 155, 158, 159, 172, 173, 190, 191, 201, 211, 225 Urodynamic, 95, 225 Uterus, 164, 165, 169, 171, 181, 225, 226 V Vaccination, 225, 226 Vaccine, 150, 211, 225, 226 Vaccinia, 97, 226 Vacuole, 6, 14, 226 Vagina, 165, 172, 226 Valproic Acid, 108, 226 Variola, 226 Vascular, 89, 93, 94, 106, 107, 109 Vascular endothelial growth factor, 62, 226 Vascular Resistance, 30, 89, 152, 179, 226 Vasculitis, 94, 226 Vasoactive, 105, 226 Vasoconstriction, 177, 226
Vasodilatation, 190, 200, 226 Vasodilation, 89, 158, 200, 203, 226 Vasodilator, 54, 100, 160, 174, 179, 181, 185, 190, 192, 197, 199, 200, 203, 204, 206, 224, 226 Vector, 224, 226 Vein, 94, 153, 189, 201, 215, 226 Venlafaxine, 18, 226 Venous, 94, 95, 111, 160, 200, 201, 211, 226, 227 Venous Pressure, 111, 226 Venous Thrombosis, 94, 95, 226, 228 Ventilation, 7, 226 Ventilator, 194, 214, 226 Ventricle, 10, 157, 212, 218, 222, 226, 227 Ventricular, 4, 10, 67, 107, 109, 118 Ventricular fibrillation, 39, 227 Ventricular Function, 31, 227 Venules, 160, 162, 227 Vertigo, 93, 180, 227 Vesicular, 8, 185, 218, 226, 227 Veterinary Medicine, 133, 227 Vinblastine, 73, 112, 113, 227 Vinca Alkaloids, 227 Vincristine, 28, 57, 73, 75, 76, 227 Viral, 9, 97, 119, 155, 224, 227, 228 Virulence, 157, 224, 227 Virus, 119, 155, 157, 164, 185, 189, 207, 218, 224, 226, 227, 228 Virus Diseases, 155, 227 Visual Acuity, 105, 169, 227 Visual field, 105, 202, 227 Vitreous Body, 214, 227 Vitro, 7, 9, 13, 17, 72, 73, 76, 84, 184, 227 Vivo, 7, 13, 14, 74, 88, 89, 227 Voltage-gated, 6, 10, 227 W Warfarin, 100, 227 Warts, 185, 208, 228 White blood cell, 114, 149, 154, 191, 193, 196, 207, 228 Withdrawal, 4, 66, 228 X Xanthine, 152, 228 Xanthine Oxidase, 152, 228 Y Yeasts, 162, 206, 228 Z Zoster, 119, 228 Zygote, 168, 228 Zymogen, 211, 228
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Verapamil
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248
Verapamil
