CARDIOMYOPATHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
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., 1960Cardiomyopathy: 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: 0-597-84366-X 1. Cardiomyopathy-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 cardiomyopathy. 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 CARDIOMYOPATHY .................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Cardiomyopathy............................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 70 CHAPTER 2. NUTRITION AND CARDIOMYOPATHY....................................................................... 119 Overview.................................................................................................................................... 119 Finding Nutrition Studies on Cardiomyopathy......................................................................... 119 Federal Resources on Nutrition ................................................................................................. 126 Additional Web Resources ......................................................................................................... 126 CHAPTER 3. ALTERNATIVE MEDICINE AND CARDIOMYOPATHY ................................................ 129 Overview.................................................................................................................................... 129 National Center for Complementary and Alternative Medicine................................................ 129 Additional Web Resources ......................................................................................................... 135 General References ..................................................................................................................... 138 CHAPTER 4. DISSERTATIONS ON CARDIOMYOPATHY .................................................................. 139 Overview.................................................................................................................................... 139 Dissertations on Cardiomyopathy.............................................................................................. 139 Keeping Current ........................................................................................................................ 140 CHAPTER 5. CLINICAL TRIALS AND CARDIOMYOPATHY ............................................................. 141 Overview.................................................................................................................................... 141 Recent Trials on Cardiomyopathy.............................................................................................. 141 Keeping Current on Clinical Trials ........................................................................................... 156 CHAPTER 6. PATENTS ON CARDIOMYOPATHY ............................................................................. 159 Overview.................................................................................................................................... 159 Patents on Cardiomyopathy....................................................................................................... 159 Patent Applications on Cardiomyopathy ................................................................................... 182 Keeping Current ........................................................................................................................ 212 CHAPTER 7. BOOKS ON CARDIOMYOPATHY................................................................................. 213 Overview.................................................................................................................................... 213 Book Summaries: Federal Agencies............................................................................................ 213 Book Summaries: Online Booksellers......................................................................................... 214 Chapters on Cardiomyopathy..................................................................................................... 217 CHAPTER 8. PERIODICALS AND NEWS ON CARDIOMYOPATHY ................................................... 223 Overview.................................................................................................................................... 223 News Services and Press Releases.............................................................................................. 223 Academic Periodicals covering Cardiomyopathy ....................................................................... 228 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 229 Overview.................................................................................................................................... 229 U.S. Pharmacopeia..................................................................................................................... 229 Commercial Databases ............................................................................................................... 230 Researching Orphan Drugs ....................................................................................................... 231 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 235 Overview.................................................................................................................................... 235 NIH Guidelines.......................................................................................................................... 235 NIH Databases........................................................................................................................... 237 Other Commercial Databases..................................................................................................... 239 The Genome Project and Cardiomyopathy................................................................................. 239 APPENDIX B. PATIENT RESOURCES ............................................................................................... 245
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Overview.................................................................................................................................... 245 Patient Guideline Sources.......................................................................................................... 245 Associations and Cardiomyopathy............................................................................................. 249 Finding Associations.................................................................................................................. 251 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 253 Overview.................................................................................................................................... 253 Preparation................................................................................................................................. 253 Finding a Local Medical Library................................................................................................ 253 Medical Libraries in the U.S. and Canada ................................................................................. 253 ONLINE GLOSSARIES................................................................................................................ 259 Online Dictionary Directories ................................................................................................... 262 CARDIOMYOPATHY DICTIONARY ...................................................................................... 265 INDEX .............................................................................................................................................. 355
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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 cardiomyopathy 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 cardiomyopathy, 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 cardiomyopathy, 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 cardiomyopathy. 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 cardiomyopathy, 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 cardiomyopathy. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON CARDIOMYOPATHY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on cardiomyopathy.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and cardiomyopathy, 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 “cardiomyopathy” (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: •
Uremic Cardiomyopathy: Reducing the Cardiac Burden in End-Stage Renal Disease Source: Journal of Critical Illness. 13(10): 613-615, 619-623. October 1998. Contact: Available from Cliggott Publishing Company. 55 Holly Hill Lane, Greenwich, CT 06831-0010. (203) 661-0600. Summary: Left ventricular (LV) hypertrophy and dilatation and systolic dysfunction are common in patients receiving hemodialysis and are associated with significantly decreased survival and increased morbidity. In this article, the authors discuss abnormalities of LV structure and function. They cover the diagnosis of uremic cardiomyopathy, review data on the prevalence and outcomes of LV dysfunction, and explore interventions relevant to the management of these patients. Echocardiography is the standard diagnostic tool for cardiomyopathy in patients with end-stage renal
4
Cardiomyopathy
disease (ESRD). The use of echocardiography to differentiate diastolic from systolic dysfunction can help guide patient management. With few controlled clinical trials specifically examining cardiomyopathy in uremic patients, management generally follows guidelines from studies in the general population. Aims of therapy are to improve quality of life by controlling symptoms of heart failure, ischemic heart disease, cardiac arrhythmias, and dialysis-associated hypotension; and to correct modifiable risk factors, such as hypertension, anemia, uremia, malnutrition, and aortic stenosis. Drug therapy requires great caution in this patient population, and should be begun only after careful consideration of risk and benefit. 1 figure. 6 tables. 38 references. (AA-M). •
Diabetic Cardiomyopathy: A Unique Entity or a Complication of Coronary Artery Disease? Source: Diabetes Care. 18(5): 708-714. May 1995. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article explores diabetic cardiomyopathy. The author notes that the three major factors in diabetic heart disease are coronary artery disease, autonomic neuropathy causing cardiac denervation, and diabetic cardiomyopathy. The article covers autopsy studies, animal studies, clinical studies, noninvasive and invasive human cardiac studies, the etiology of diabetic cardiomyopathy, and treatment issues. The author concludes that increased mortality from cardiac disease in the diabetic population is not entirely attributable to ischemic heart disease and may well be caused by diabetic cardiomyopathy. Treatment of diabetic cardiomyopathy should include glycemic control, use of appropriate antihypertensive therapy, and early detection and correction of myocardial ischemia. 79 references.
Federally Funded Research on Cardiomyopathy The U.S. Government supports a variety of research studies relating to cardiomyopathy. 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 cardiomyopathy. 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 cardiomyopathy. The following is typical of the type of information found when searching the CRISP database for cardiomyopathy:
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
•
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Project Title: 4-DIMENSIONAL LV TISSUE TRACKING IN CAD FROM TAGGED MRI Principal Investigator & Institution: Amini, Amir A.; Assistant Professor; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: (Adapted from Applicant's Abstract): The applicants propose to develop and validate new image analysis methods aimed at a more accurate, reproducible, and automated approach to assessment of regional left ventricular (LV) function and visualization of 3D cardiac motion from tagged MRI data of patients with coronary artery disease (CAD). The applicants have developed a number of methods for analysis of tagged MRI data which have been validated in phantoms and animal models of myocardial infarction (MI). They propose to continue development of these techniques which utilize all of the available stripe information, including tag intersections and linear tag lines, in automatically taking LV deformations and reconstructing dense displacements at all myocardial points, with the goal of routinely applying these techniques to patient data. The advantage of the developed methods is that since displacement vectors will be available at all myocardial points, indices of LV function will also be available everywhere in the myocardium. These indices can be summed over local myocardial regions resulting in segmental function scores. In human studies, the developed methods will be applied to images acquired from normal volunteers, patients with pharmacologic stress-induced myocardial ischemia, patients with old, healed MI, and patients with ischemic dilated cardiomyopathy. In each case, segmental wall motion as assessed by the algorithms will be compared and correlated with validated clinical techniques such as 2D echocardiography, cine-MRI, and Gadolinium (Gd) contrast MRI. Thus, the specific aims are: (a) To measure statistical distribution (mean and standard deviation) of segmental function scores from 3D + t (short-axis and long-axis) tagged MRI at rest and under pharmacologic (dobutamine) stress in normal controls. (b) To measure the function scores as determined from 2D + t (short-axis) tagged MRI during pharmacologic stress and classified into normal, hypokinetic, or akinetic classes in patients with stress-induced ischemia. These labels will then be statistically correlated to labels assigned to the same segments by 2D echocardiography and cine-NIRI. (c) To measure segmental function scores as determined from 3D + t (short-axis and long-axis) tagged NIRI at rest and classified into normal, hypokinetic, akinetic, or dyskinetic classes in patients with an old, healed MI. The labels will be statistically compared to non-nal or akinetic labels assigned to the same segment from 2D echocardiography and cine-MRI, and with Gd contrast MRI. (d) To measure the segmental function scores from 3D + t (short-axis and long-axis) tagged MRI at rest and classified into normal, hypokinetic, akinetic, or dyskinetic classes in patients with ischemic, dilated cardiomyopathy. The labels will be statistically compared to labels assigned to the same segment from 2D echocardiography and cine-MRI. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: AGING, CARDIOMYOPATHY
INSULIN
RESISTANCE,
AND
DILATED
Principal Investigator & Institution: Shannon, Richard P.; Professor of Medicine; Allegheny-Singer Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Congestive heart failure is a leading cause of morbidity and mortality in the elderly, although the mechanisms to explain the
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Cardiomyopathy
enhanced proclivity are poorly understood. It remains debatable as to whether the ageassociated propensity to cardiovascular dysfunction is attributable to aging per se or the accumulation of cardiovascular risk factors that accrue over time. In particular, aging has been closely associated with the development of increased visceral adiposity that has been implicated in the pathogenesis of age associated insulin resistance. Whether age associated insulin resistance contributes to the progression of cardiac dysfunction following myocardial injury has not been explored systematically. The altered cellular actions of insulin that underlie physiological insulin resistance may have significant consequences to the failing heart. The injured myocardium develops an evolving dependence on glucose as its preferred metabolic substrate. The preference is dependent upon the efficiencies of oxidation of glucose in the generation of high-energy phosphates. This preference becomes a requirement as the ability to oxidized fat acids is limited through a series of molecular switches in key regulatory components of fatty acid transport and oxidation. We have determined that advanced, decompensated stages of dilated cardiomyopathy are associated with the development of myocardial insulin resistance, which limits myocardial glucose uptake and oxidation. These physiological features are associated with cellular insulin signaling abnormalities in the myocardium that are distinct from those observed in skeletal muscle and adipose tissue in other insulin resistant states. Together, aging and heart failure share the common pathophysiological features of insulin resistance. Whether the effects are additive or synergistic in explaining the increased incidence and severity of heart failure in the elderly remains to be determined. We will determine if aging is associated with accelerated progression of heart failure in conscious dogs with pacing induced dilated cardiomyopathy. We will define the physiological and cellular effects of insulin resistance in the senescent myocardium during the evolution of dilated cardiomyopathy. Finally, we will determine if overcoming myocardial insulin resistance in the aging and failing heart will prevent the progression of dilated cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AKT CARDIOMYOPATHY
ACTIVATION
AS
TREATMENT
FOR
DILATED
Principal Investigator & Institution: Sussman, Mark A.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (the applicant's description verbatim): Primary degenerative changes in the failing heart include remodeling associated with loss of structural organization and cardiomyocyte apoptosis. Optimal treatment strategies must approach the long term goal of a molecular approach that promotes myocardial integrity and inhibits apoptosis to prevent ventricular dilation. Myocardial pathogenesis is inhibited by activation of Akt kinase, although the potential therapeutic effect of Akt activation has never been examined in the context of dilated cardiomyopathy. Recent results have demonstrated nuclear translocation of activated Akt correlates with prevention of dilation in mouse transgenic models of cardiomyopathy. The hypothesis of this proposal is that nuclear translocation of activated Akt inhibits the initiation and progression of dilation and heart failure. Insulin-like growth factor-1 (IGF-1) or the cellular oncogene Tcl-1 initiate nuclear translocation of Akt. In addition, we have discovered similar Akt activation by genistein, a phytoestrogen compound found in soy-based dietary products that exhibits estrogen agonist properties. Innovative approaches to be used involve mice that are genetically engineered or pharmacologically treated to activate Akt, with concurrent experiments to demonstrate beneficial effects of Akt activation in rescuing a transgenic
Studies
7
mouse model of dilated cardiomyopathy. The specific aims are: 1) to reproducibly and precisely induce Akt activation by IGF-1, genistein treatment, and Tcl-l expression; 2) to prevent pathologic and degenerative changes by activation of Akt; 3) to show that beneficial effects of Akt activation are dependent upon induction of phosphoinositide 3kinase. Biochemical, molecular, and confocal microscopic approaches used in combination will demonstrate the efficacy of Akt activation by the various inductive stimuli as well as the impact of the different treatments upon the pathogenesis of dilation. The significance of the study is the identification and characterization of a therapeutic pathway for treatment of heart failure, along with new approaches for the activation of Akt in the heart. This study will demonstrate the relationship between Akt activation and inhibition of cardiomyopathy, providing novel directions for therapeutic treatment to induce Akt translocation and mitigate heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALCOHOL MODULATION OF CARDIAC CALCIUM CHANNELS Principal Investigator & Institution: Aistrup, Gary L.; Mol Pharm & Biol Chemistry; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Alcohol exerts a variety of actions on the cardiovascular system, the nervous system, and other organs. Clinical studies, have linked alcohol consumption with a number of asymptomatic and overt cardiovascular abnormalities, including cardiomyopathy, hypertension, arrhythmias, heart failure, and stroke. The mechanisms responsible for these various problems are not well understood. In the nervous system, voltage activated calcium channels and certain ligand-gated channels arc particularly sensitive targets of alcohol. These channels are suspected of being instrumental in acute intoxication and withdrawal. In cardiac tissues, calcium channels play a key role in rhythmicity, conduction, and excitation-contraction coupling. These channels are a major site of control by endogenous hormones and transmitters, and by therapeutic drugs. Calcium channels have been directly linked to a number of the actions of ethanol on the heart. Ethanol interferes with contractility in a variety of models, and it reduces electrically-stimulated calcium transients in ventricular myocytes. Our preliminary data with rat myocytes, and results from other laboratories, have confirmed that ethanol blocks L-type calcium channels in isolated cardiac cells. Defining how alcohol affects the physiology and regulation of these channels is essential in explaining immediate consequences of alcohol ingestion, as well as events that occur during prolonged periods of alcohol ethanol abuse. The overall objective of the proposed studies is to use whole-cell patch clamp techniques to analyze ethanol modulation of cardiac calcium channels. Ventricular myocytes will be dissociated from cardiac tissues of adult rats, and subjected to acute alcohol exposure. Biophysical and pharmacological experiments will evaluate calcium channel function under these conditions, and impossible mechanisms of channel modulation. Certain second messenger systems are known to exert regulatory control over calcium channel function in heart cells. Among these, the betaadrenergic/cAMP/PKA pathway is a critical mechanism for enhancing L-type calcium channels and stimulating cardiac contractility. We will therefore test the hypothesis that ethanol alters regulation of channels through this signal transduction system. Our preliminary data have shown that ethanol not only blocks currents stimulated via the beta-adrenergic system, but it also inhibits desensitization of the coupling process. We have also just completed exciting new preliminary studies demonstrating that ethanol is capable of reversing or occluding nifedipine-induced channel block. This novel action may have major implications, given the widespread clinical use of dihydropyridines
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Cardiomyopathy
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: ANIMAL MODELS OF HYPERTROPHIC CARDIOMYOPATHY Principal Investigator & Institution: Robbins, Jeffrey; Professor and Director; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the Investigator's Abstract) Familial hypertrophic cardiomyopathy, a major cause of sudden death, is caused by mutations in the genes encoding various components of the cardiac contractile apparatus. The applicant proposes to use a combination of molecular, genetic and functional approaches to understand the pathological processes that occur in the heart as a result of the expression of the mutant proteins in patients with FHC. Using the technique of cardiac specific transgenic overexpression, specific contractile protein isoforms in the cardiac compartment can be replaced in transgenic animals and thereby the functional consequences of the mutations over the lifetime of the animal can be established. Specifically, four constructs will be used, each of which contains a mutation in the sequence known to be associated with FHC:. ELC (essential light chain) (MET 149 VAL), MLC regulatory light chain (GLU 22 LYS), the ILE79ASN mutation in cardiac troponin T, and the truncation mutation in MHC binding protein C (delta 845-1189). The dosedependent consequences of the expression of these mutant proteins will be studied by analyzing multiple transgenic lines. A rabbit model of FHC will be generated using the two light chain constructs, since rabbit heart is more representative of the human organ. The data to be obtained from the rabbit lines when compared with the ongoing mouse studies will allow an assessment of the murine models applicability to the large animal heart and together these models should prove to be invaluable in increasing our understanding of how the primary genetic etiology contributes to the developing hypertrophic response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ANNEXIN II EXPRESSION DURING CARDIOVASCULAR CELL INJURY Principal Investigator & Institution: Hajjar, Katherine A.; Professor & Chairman; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: Vascular cells within the heart and blood vessels are subject to an array of signals which induces adaptive responses for the maintenance of homeostasis. Because cardiomyocytes are incapable of self-renewal, the heart possesses limited means of responding to biochemical, inflammatory, oxidative, or ischemic stresses. Annexin II is a calcium- regulated, phospholipid-binding endothelial cell surface protein that serves as a co-receptor for endothelial cell derived tissue plasminogen activator and its circulating substrate, plasminogen. Purified annexin II stimulates the catalytic efficiency of plasmin generation by approximately 60-fold. We have developed an annexin II-deficient mouse and observed that these animals develop a degenerative cardiomyopathy with impaired myocardial function. We have further observed that, in endothelial cells propagated in vitro, annexin II is exported to the cell surface via a non- classical secretion pathway in response to stress. The overall goal of this project is to understand the role of annexin II in cardiac function both at baseline and during states of cellular stress. We hypothesize
Studies
9
that annexin II may play a critical cardioprotective role by maintaining the integrity of the myocardial microvascular circulation. Aim I will to determine the cardiovascular consequences of annexin II deficiency in mice. Using our recently developed annexin II knockout mouse, we will study the mechanism by which annexin II deficiency may lead to reduced myocardial contractility, abnormal ventricular architecture and cardiac arrthymia. Aim II will be able to determine the mechanism by which annexin II participates in the endothelial cell stress response. Preliminary data indicate that heat shock and other endothelial stresses lead to protein synthesis-independent, rapid release of annexin II to the cell surface with a concomitant increase in cell surface fibrinolytic activity. This export process does not require an intact endoplasmic reticulum-Golgi axis, and is inhibited by PD98059, an agent that blocks activation of the Erk1/Erk2 MAP kinase signaling cascade. We plan to elucidate this export mechanism and to determine its effect on endothelial cell function. Aim III, finally, will e to determine whether annexin II is cardioprotective during cardiovascular stress states in vivo. Annexin II has been found to be up-regulated in the hearts of humans and animals with cardiac dysfunction. Using models of acute, subacute and chronic stress induced by adrenergic stimuli, exercise, heat stress, biome3chanical compromise, or oxidant agents, we will determine whether annexin II protects against cardiovascular compromise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: APOPTOSIS CARDIOMYOPATHY
AND
CONTRACTILITY
IN
ISCHEMIC
Principal Investigator & Institution: Canty, John M.; Professor; Medicine; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2002; Project Start 10-JAN-2000; Project End 31-DEC-2003 Summary: Ischemic cardiomyopathy is the most common etiological cause of heart failure but the factors responsible for initiating decompensated LV dysfunction are unknown. Although considerable work has focused on irreversible injury following infarction, many patients have symptoms of heart failure in association with viable dysfunctional or "hibernating" myocardium. Pathological studies support the notion that the degree of dysfunction frequently exceeds the amount of structural fibrosis identified at postmortem exam. Preliminary studies by the applicant have reproduced the physiological features of hibernating myocardium in pigs with a chronic LAD stenosis. While this occurs with normal LV function and without infarction, there is increased regional myocyte apoptosis, a 30 percent loss of myocytes and compensatory myocyte hypertrophy after a period of 3 months. At the molecular level, there is a regional downregulation of SR calcium uptake proteins. These changes, arising from reversible ischemia (i.e. angina pectoris) and with normal global LV function, are identical to the abnormalities found in end-stage heart failure. Thus, the overall hypothesis of this application is that myocyte apoptosis and SR dysfunction arise in areas with chronically reduced coronary flow reserve and are early rather than late events in the pathogenesis of ischemic cardiomyopathy. Aim 1 will define the role of apoptosis mediated myocyte loss and LV remodeling from reversible ischemia in hibernating myocardium. A 2-vessel stenosis model that progresses to global LV dysfunction with LV dilatation and increased LV filling pressure will be used to determine how diastolic stretch and the size of the dysfunctional region modulates apoptosis and LV remodeling. Aim 2 will identify the temporal progression of apoptosis in ischemic and normal regions in relation to the expression of the pro- and antiapoptotic proteins Bax and Bcl-2 which will be quantified in vivo on a regional basis. Aim 3 will define the extent that apoptosis mediated myocyte loss and altered SR
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Cardiomyopathy
protein expression affects the reversibility of function in hibernating myocardium after surgical revascularization and after stimulating angiogenesis with basic fibroblast growth factor (FGF-5). Aim 4 will determine whether apoptosis and altered SR protein expression can be prevented pharmacologically with beta blockade, by stimulating angiogenesis prior to the development of myocyte loss and by overexpressing Bcl-2 in vivo. This integrative approach should provide a better understanding of the events that lead to the progression of ischemic LV dysfunction at a time when therapeutic interventions such as revascularization and in vivo gene transfer can be used to interrupt the progressive myocyte loss, contractile dysfunction and irreversible structural fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BETA-ADRENERGIC HYPERTROPHY/FAILURE
RESPONSE
IN
CARDIAC
Principal Investigator & Institution: Bond, Meredith; Professor and Chair; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-MAY-2005 Summary: (provided by applicant): Alterations in the signal transduction pathways which regulate Ca2+ dependent force in the heart contribute to the impaired contractile function in heart failure. These functional changes are likely to be mediated by altered phosphorylation of cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) substrates. One of the major PKA/PKC substrates in the cardiac muscle cell is the thin filament regulatory protein, troponin I (TnI). As a result of conformational changes in the TnI molecular upon phosphorylation of the different PKA and PKC sites TnI, interactions between TnI with other proteins of the thin filament - and thus contractile function - are altered. In other words, TnI and its phosphorylation fingerprint represent a critical control point in the pathway regulating contractile state as a function of the incominb Ca2+ signal. We have shown that PKA phosphorylation of TnI is decreased by 25% in human heart failure. This results in increased Ca2+ affinity of troponin C (TnC), and may contribute to enhanced myofilament Ca2+ sensitivity, and prolonged relaxation of failing hearts. In contrast, PKC is reportedly increased in failing hearts; increased PKC phosphorylation of one or more sites on TnI decreases maximal actomyosin (AM) ATPase activity and thus could also contribute to impaired contraction in heart failure. However, reports on the effect of elevated PKC activity on TnI phosphorylation and cardiac function are conflicting. Finally, activity of protein phosphatases - protein phosphatase 1 (PP1) and/or PP2A - will also determine the phosphorylation state of TnI. In Specific Aim 1, we will identify the complete phosphorylation profile of TnI in failing human hearts with dilated cardiomopathy (DCM) and compare this with non-failing hearts. Electrospray ionization mass spectrometry (ESI/MS) will be used to quantify stoichiometry of the phosphorylated residues in tryptic digests of TnI obtained from failing and non-failing hearts, by a rapid one-step isolation to trop the in vivo phosphorylation state. In Specific Aim 2, we will (a) examine conformational changes that result from the combined changes of PKC and PKA phosphorylation of TnI in failing vs non-failing hearts. This will be achieved by measurement of fluorescence quenching tryptophan residues in cTnI, with selected serines and threonine mutated to aspartates or alanines, then reconstituted with human cardiac TnT and TnC. (b) The functional consequences of altered TnI phosphorylation will be assessed by measurement of Ca2+ dependent force in skinned cardiac trabeculae from failing and non-failing hearts. Specific Aim 3 will test the hypothesis that activity of TnI targeted phosphatases is altered in failing hearts. These studies should provide
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new information on the complete complement of changes in PKA and PKC-dependent TnI phosphorylation in human heart failure. Structural and functional outcomes of these changes plus identification of the altered phosphatase activity will shed light on mechanisms responsible for the functional decline in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOMEDICAL STRESS PATHWAYS AND CARDIOMYOPATHY Principal Investigator & Institution: Chien, Kenneth R.; Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 25-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The interaction between biomechanical stimuli, such as pressure and volume overload, with discrete hypertrophy, survival, and cell death pathways, plays an important role in the initiation of cardiomyopathy and heart failure. Project 1, ?Biomechanical Stress Pathways and Cardiomyopathy? (K.R. Chien), focuses on molecular pathways that mediate biomechanical stress-induced cardiac responses, based on new genetic pathways for cardiac hypertrophy and cardiomyopathy. The project utilizes unique genetically engineered animal models and novel physiological technology to dissect complex phenotypes in living animals, cardiac papillary muscle preparations, and single cardiac myocytes. Continuing our longstanding interest in pg130 pathways for cardiac hypertrophy and myocyte survival, we have recently identified a downstream component (SOCS3) in the gp130 pathway as being rapidly and markedly induced following in vivo pressure overload. SOCS3 is part of a stressinducible negative feedback loop that prevents the hyper-stimulation of the gp130 pathway. These studies will examine the role of SOCS3 inhibition as a new therapeutic strategy to promote myocyte survival and to prevent the onset of diverse forms of cardiomyopathy. In continuation of our previous studies on the role of mutations in the Z disc protein MLP in dilated cardiomyopathy, we have recently identified MLP as part of the endogenous titin-telethonin complex. This MLP-telethonin interaction is critical for the maintenance of the stretch induced hypertrophy response. We have recently uncovered a mutation in MLP that is associated with human dilated cardiomyopathy in patients with idiopathic forms of the disease. The point mutation results in a severe charge change in a highly conserved residue in the telethonin interacting domain of MLP located in the aminoterminus and interrupts the ability of MLP to interact with telethonin, a known genetic cause of human cardiomyopathy. Similarly, we have identified patients with a deletion in the MLP interacting domain of telethonin. Accordingly, the specific aims are: 1) to identify the effects of the SOCS3 negative feedback loop on cardiac hypertrophy, myocyte survival, and cardiomyopathy in multiple model systems via studies of cardiac restricted SOCS3 KO mice; 2) to directly examine the effects of human mutations in MLP on biomechanical stretch responses and specific features of dilated cardiomyopathy; and 3) to examine the effects of mutations in specific domains of telethonin and telethonin phosphorylation on MLP binding, stretch activation responses, and dilated cardiomyopathy in genetically engineered mouse model systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CALCIUM CYCLING AND REGULATION OF THE CARDIAC AP Principal Investigator & Institution: Winslow, Raimond L.; Professor; Biomedical Engineering; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 31-MAR-2006
12
Cardiomyopathy
Summary: Dilated cardiomyopathy (DCM) is the most common form of primary cardiac muscle disease, with prevalence estimated at 36.5 cases per 100,000. DCM is characterized by ventricular dilation, decreased myocardial contractility and cardiac output, and increased risk of sudden cardiac death. Ventricular myocytes isolated from failing hearts exhibit changes in expression levels of proteins involved in repolarization of the action potential (AP) and intracellular calcium (Ca2+) cycling. These changes are accompanied by reduction of junctional sarcoplasmic reticulum (JSR) Ca2+ concentration, peak intracellular Ca2+ transient amplitude, slowed diastolic Ca2+ extrusion and prolongation of AP duration. We have previously formulated a "minimal" computational model of the failing canine ventricular myocyte that incorporates experimental data on down-regulation of potassium (K+) currents and the SR Ca2+ATPase, and up-regulation of the Na+-Ca2+ exchanger. This model is able to qualitatively reconstruct changes in AP and Ca2+ transient morphology observed in failing myocytes. Model simulations predict that down- regulation of the SR Ca2+ATPase by itself produces significant prolongation of AP duration by reducing JSR Ca2+ level, JSR Ca2+ release and the magnitude of Ca2+-dependent inactivation of L-type Ca2+ current (ICa,L). This decreased Ca2+-dependent inactivation increases ICa,L during the plateau phase, thereby increasing AP duration. These model predictions are supported by results of preliminary experiments. This has led us to hypothesize that JSR Ca2+ level through effects on JSR Ca2+ release and Ca2+-dependent inactivation of ICa.L, modulates AP duration, and that this modulation is important under a range of conditions producing changes in JSR Ca2+ level, including heart failure. The general goal of the proposed research is to test this hypothesis by means of experiments coupled with computational modeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CALMODULIN CARDIOMYOPATHY
KINASE
AND
ARRHYTHMIAS
IN
Principal Investigator & Institution: Anderson, Mark E.; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Arrhythmias cause 50% of deaths in patients with cardiomyopathy and heart failure. Recent findings have highlighted the importance of Ca2+-activated kinases and phosphatases in activating gene programs driving morphological and functional changes in cardiomyopathy. One focus of our previous studies has been the arrhythmogenic potential of Ca2+/calmodulin-activated protein kinase (CaMK) II in normal cardiomyocytes with drug-induced action potential prolongation. More recently, we have developed evidence for an arrhythmogenic phenotype in cardiomyopathy that consists of increased CaMKII expression and activity, action potential and QT interval prolongation, disordered intracellular Ca2+ homeostasis, and arrhythmias or sudden death. The goal of this Project is to test the hypothesis that CaMKII is a molecular link between functional and morphological phenotypes, and thus a contributor to arrhythmia susceptibility in cardiomyopathy. To accomplish this goal, two distinct and well-characterized mouse models with cardiomyopathy, increased CaMKII activity, and arrhythmias will be interbred with mice that we have developed with cardiac-specific expression of a CaMKII inhibitory protein, or an inactive control. Using these tools, we will determine the effect of chronic CaMKII inhibition on the arrhythmogenic and the morphological and functional phenotypes in cardiomyopathy. To further understand the mechanisms underlying the salutary effects of CaMKII inhibition, we will determine the effect of chronic, cardiac-
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targeted CaMKII inhibition on potential downstream signaling pathways. These experiments will target an arrhythmogenic molecular mechanism and build from single molecule assays to biochemical, histological, and functional studies in the whole heart. Delineation of the role of CaMKII in arrhythmogenesis will be an important step in developing new antiarrhythmic therapies in patients with heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIAC DISEASE IN COOLEYS ANEMIA--MOLE AND CLIN STUDIES Principal Investigator & Institution: Brittenham, Gary M.; Professor of Medicine; Anatomy and Cell Biology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2004 Summary: The proposed research project is designed to characterize the molecular pathophysiology and clinical consequences of iron-induced cardiac disease using a coordinated series of studies of cardiac myocytes in culture, of the first animal model of the cardiomyopathy of iron overload, and of patients with thalassemia major. Ironinduced myocardial disease is the most frequent cause of death in thalassemia major and is a major life-limiting complication of other transfusion- dependent refractory anemias hereditary hemochromatosis and other forms of iron overload. We hypothesize that (i) the body iron burden is a principal determinant of the magnitude of cardiac iron deposition in patients with thalassemia major, (ii) the nonuniform pattern of iron deposition in the heart results in variability in iron concentrations within cardiac myocytes, and (iii) the increased intracellular iron selectively affects specific ion channels in cardiac myocytes, producing abnormalities in sodium and potassium currents that result in aberrant ventricular repolarization and contribute to arrhythmogenesis. The proposed research has three specific aims: (1) to determine the pathophysiologic mechanisms responsible for iron-induced abnormalities of Na+ and K+ currents in cultured neonatal rat cardiac myocytes and the effects of iron chelators, antiarrhythmic drugs and other agents; (2) to examine the effects of excess iron, iron chelators, antiarrhythmic drugs and other agents on cardiac electrophysiology and function in a gerbil model of iron overload both in the intact animal and in isolated heart preparations; and (3) to determine the relationship in patients with thalassemia major between body iron burden, as measured by non- invasive magnetic susceptometry, and abnormalities of cardiac rhythm and function, as assessed as assessed by the signalaveraged electrocardiogram, T wave alternans, dynamic measures of the QT interval and echocardiography. This research will result in new fundamental information about the molecular basis for the effects of iron on cardiac ion channels, will provide the first electrophysiolgical and functional studies in a new animal model of iron overload, and will develop new non-invasive means of identifying those patients at the highest risk for iron-induced cardiac disease to permit intensive iron chelation therapy and other preventive interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIAC REGULATION
HYPERTROPHY
INDUCED
METABOLIC
GENE
Principal Investigator & Institution: Barger, Philip M.; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 08-APR-1998; Project End 31-MAR-2003
14
Cardiomyopathy
Summary: Cardiac hypertrophy and congestive heart failure are significant causes of morbidity and mortality in the United States. The human heart undergoes hypertrophic growth in response to pathophysiologic stimuli such as chronic hypertension and valvular disease. The transition from normal to hypertrophied ventricle is marked by characteristic molecular phenotypic changes, including a switch in the energy metabolic gene regulatory program from predominantly fatty acid beta-oxidation (FAO) to the more oxygen-efficient glycolysis, a reactivation of fetal metabolism. Little is known about the hypertrophy signaling pathway linked extracellular stimulus to transcriptional regulation. The broad goals of this proposal are to delineate the molecular regulatory signals which ultimately contribute to down-regulation of FAO during hypertrophy. This proposal is specifically designed to i) characterize alterations in fatty acid beta-oxidation gene transcription in cultured rat neonatal cardiocytes undergoing hypertrophy and to delineate the specific cis-acting elements mediating that response utilizing Northern and Western blot analysis, RNase protection, and transient gene transfer studies with FAO enzyme gene promoters; ii) identify the specific transcriptional regulators that bind to the responsive elements in the promoters of betaoxidation genes during cardiocyte hypertrophy utilizing electrophoretic mobility shift assay, cotransfection, Northern and Western blot analysis, RNase protection, and immunofluorescence; iii) determine whether the activity of the regulators are increased during hypertrophy by phosphorylation events utilizing in vitro and in vivo phosphorylation studies, inhibitors of known signal transduction cascades, and phosphorylation site mutations with emphasis on the mitogen-activated protein kinase pathway. The longterm goals will be to determine whether reactivation of this fetal metabolic gene program and/or downregulation of fatty acid beta-oxidation leads to a maladaptive hypertrophied phenotype and thus promotes the transition to heart failure. If so, the studies outlined above will have identified potential targets for therapeutic interventions aimed at delaying or even preventing progression to end-stage cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIAC KATP CHANNELS IN HEALTH AND DISEASE Principal Investigator & Institution: Terzic, Andre; Professor of Medicine and Pharmacology; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2004; Project Start 01-APR-2000; Project End 31-MAR-2008 Summary: (provided by applicant): Cardiac ATP-sensitive K (KATP) channels, formed by the pore-forming Kir6.2 and regulatory SUR2A subunits, are characterized by nucleotide-dependent regulation that allows the channel complex to adjust membrane excitability in response to changes in the cellular energetic state. However, it is unknown how cardiac KATP channels translate nucleotide signals into pore gating, what is the full impact of channel activity on cardiac homeostasis, and ultimately whether channel defects contribute to heart disease. In the previous funding period of this proposal we identified an ATPase activity intrinsic to the SUR2A subunit, demonstrated that deficient KATP channel function reduces cardiac tolerance to adrenergic challenge, and discovered KATe channel mutations in initial screening of patients with heart failure. Based on these findings, we here put forward the novel concept that cardiac KATP channels operate as a bi-functional channel/enzyme molecular combination serving a vital role under diverse stressors. Aim #1 will define the molecular mechanisms governing the SUR2A catalysis-based nucleotide gating of the Kir6.2 pore. Aim #2 will establish the impact of KATP channels on prevention of maladaptive structural remodeling, and preservation of energetic and electrical stability
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in the physiologically and pathologically stressed myocardium. Aim #3 will determine the spectrum of cardiac KATP channel mutations in patients with idiopathic dilated cardiomyopathy, and define the consequences of these mutations on the KATP channel/enzyme phenotype, metabolic sensing and cell adaptation to stress. To this end, we will employ murine knockout and disease models, along with genomic specimens from an existing cohort of patients with cardiomyopathy. The complementary technologies of enzymology, electrophysiology, physiological genomics, high-throughput DNA screening and functional proteomic analysis will be applied to study the cardiac KATP channel at the organism, organ, cellular and molecular levels. Thus, this proposal will provide an integrated understanding of cardiac KATP channels in metabolic signal decoding, stress adaptation, and their impact for clinical medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIOMYOPATHY IN DIABETES Principal Investigator & Institution: Lewinter, Martin M.; Professor of Medicine and Molecular Phys; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Patients with diabetes mellitus (DM) are subject to a high incidence of death and morbidity due to heart failure, especially following myocardial infarction (MI). These observations suggested and subsequent studies confirmed the presence of a diabetic cardiomyopathy (DBCM), indepenent of macrovascular CAD. In experimental DBCM, multiple mechanial abnormalities and potential mechanisms have been documented. However, the manifestations and mechanisms of DBCM in patients are not well understood. Using strips of myocardium obtained from patients with CAD and DM (CAD/DM) undergoing coronary bypass grafting, we have recently shown depression of the force-frequency relationship (FFR despite the fact that basal ventricular function was normal. This myocardial abnormality in CAD/DM is similar but less severe than that observed in dilated cardiomyopathy and mitral regurgitation and is reversible by forskolin, indicating that its proximate mechanism is likely a defect(s) in excitation-contraction coupling (ECC). This proposal has three aims, to be undertaken in CAD/DM patients and CAD controls: 1) delineate whether there is an in vivo counterpart of in vitro FFR depression in CAD/DM, 2) systematically study the processes involved in ECC in CAD/DM and determine if identified defects cause FFR depression, and 3) test for correlations between abnormal FFR/ECC and markers of both the metabolic effects of DM and associated vasculopathy in order to begin to characterize upstream mechanisms of DBCM. Patients will be recruited at both the University of Vermont and the New York Hospital-Cornell Medical Center. We will employ an integrated, collaborative approach including in vivo and in vitro determination of the FFR, in vitro quantification of ECC, and assessment of defects in glycolysis and vasculopathy in DM myocardium. A major strength of our experimental strategy is correlation, on an individual patient basis, of in vitro FFR depression with other variables of interest. Our long- term plan is to define the steps linkin abnormal carbohydrate metabolism and/or vasculopathy in DM to DBCM and ultimately design rational treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Cardiomyopathy
Project Title: CARDIOMYOPATHY:PRO-OXIDANT ROLE OF AZT & MGDEFICIENCY Principal Investigator & Institution: Weglicki, William B.; Professor and Chair; Medicine; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-MAR-2004 Summary: (Abstract): The pathogenesis of HIV-related cardiomyopathy remains unclear and most likely may have multifactorial causes. Clinical data have revealed that both the virus and myocarditis are present, but often in separate areas, suggesting that HIV may play an indirect cytotoxic role. Both the HIV infection and drug therapy (AZT, pentamidine) may contribute to oxidative stress and Mg wasting. Clinical studies have indicated that HIV/AIDS patients may be deficient in Mg. In our studies, we have documented that Mg-deficiency triggers oxidative cardiomyopathic inflammation. We hypothesize that the drug therapy with AZT may synergize with pentamidine and Mgdeficiency to initiate neurogenic inflammatory events leading to oxidative stress and eventual cardiomyopathy. To test this hypothesis, we propose to use a rat model and cultured cardiovascular cells to determine the prooxidant effects of AZT (Aim 1) or with co-existing Mg-deficiency to induce cardiomyopathy, and cardiac dysfunction with imposed ischemia/reperfusion (I/R) stress (Aim 2). We will assess the therapeutic interventions by NMDA and NK-1 receptor blockade and by vitamin E (Aim 3). In collaboration with Dr. A. Basile of NIH, we will also employ the murine AIDS (MAIDS) model to assess the synergistic contributions of the virus and Mg-deficiency to the oxidative pathogenesis and possible interventional therapy (Aim 4). We will employ sensitive immunochemical techniques to quantify neuropeptides and cytokines, and in collaboration with Dr. Haudenschild of the American Red Cross Holland Laboratory, to characterize histopathological progression in cardiac and skeletal muscles. Oxidative stress will be determined by measuring tissue glutathione and thiol status, accumulation of lipid peroxidation and nitric oxide products, and by free radical production and injury to isolated perfused I/R hearts. We anticipate that the information from these in vivo animal, tissue, and cellular studies may lead to potential diagnostic criteria and therapy for patients at risk of developing cardiomyopathy due to HIV disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZING RGS MUTATIONS IN CARDIOMYOPATHY Principal Investigator & Institution: Kurrasch-Orbaugh, Deborah M.; Pharmacology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-OCT-2003 Summary: (provided by applicant): The hypothesis of this proposal is that the RGS 16 protein is an integral component of the G-alpha-q/11 signaling complex, serving as a feedback inhibitor of G-alpha-q/11 signaling in stressed cardiomyocytes, thus helping to maintain cardiac homeostasis. We propose that a point mutation in the RGS box of RGS16 (D179Y) found in patients with dilated cardiomyopathy alters the conformation of the interaction surface with G-alpha-q/11 and/or other proteins in the signaling complex, rendering RGS16 D179Y to function as a dominant negative protein, ultimately contributing to dilated cardiomyopathy. To test this hypothesis, we shall explore the following specific aims: Aim 1. We shall examine the GAP and potential dominant negative activity of D179Y and wild type RGS16 proteins in several in vitro assays, including single-turnover assays, transition-state analog binding assays, and G-alpha-q Coupled steady state assays, and G-alpha-q -coupled MAPK activation; Aim 2. We will overexpress D179Y and RGS 16 proteins specifically in cardiomyocytes by employing
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the alpha-MHC promoter in transgenic mice and then characterize the onset of cardiomyocytes hypertrophy; Aim 3. We will create Rgs 16 D179Y knock-in mice and characterize the onset of dilated cardiomyopathy; Aim 4. We will continue to screen cardiac patients and healthy individuals to identify additional Rgs mutation. The primary objective of this proposal is to evaluate the causative role of the D179Y allele of RGS16 in the progression of dilated cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL EVALUATION OF NOVEL MARKERS OF MI Principal Investigator & Institution: Gerszten, Robert E.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Presently available serum markers of cardiac injury, such as the troponins, were developed as extensions of studies of these candidate proteins in basic cardiac physiology. In this proposal, we will test the following hypotheses: 1) That analysis of serum proteins from patients undergoing "planned myocardial infarction (PMI)," using unbiased proteomics technologies, will lead to the discovery of both novel markers of cardiac injury and novel serum response proteins which shed insight onto disease pathogenesis; 2) That novel markers and response proteins discovered in the setting of PMI will be valid in a heterogeneous population of myocardial infarction (MI) patients; and 3) That levels of novel markers and response proteins discovered in PMI will predict clinical outcomes in the heterogeneous MI population. Towards the goal of developing new cardiac markers, we first characterized serum from patients undergoing an alcohol septal ablation for hypertrophic cardiomyopathy, an in vivo model of human MI. In this population, we have identified peptide spectra and specific proteins that appear in the serum after myocardial injury. However, findings from this controlled patient subset must be validated in a heterogeneous patient cohort. Therefore, we will apply our preliminary data from the PMI group to the CLARITY-TIMI 28 trial, a large, double-blind, randomized clinical trial studying patients with acute ST elevation myocardial infarction (STEMI). In Specific Aim 1, we will characterize the recently identified peptide markers in the entire cohort of PMI patients. In Specific Aim 2, we will validate the novel markers in a diverse patient population of "normal myocardial infarction" in the TIMI trial. In Specific Aim 3, we will correlate elevations in novel protein markers and response proteins with outcomes in patients with acute MI in the TIMI trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTRAST MRI AND CHRONIC MYOCARDIAL INJURY IN HUMANS Principal Investigator & Institution: Kim, Raymond J.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-DEC-2005 Summary: (Verbatim from the Applicant's Abstract): Two important changes regarding contrast enhanced MRI (ceMRI) of the heart have recently occurred. First, it is now recognized that segmented k-space inversion-recovery imaging pulse sequences result in image intensities in "hyperenhanced" regions which are typically 500 percent higher than in "non hyperenhanced" regions, greatly reducing observer subjectivity. Second, recent data suggest that healed myocardial infarcts hyperenhance. In preliminary studies, the applicants found that ceMRI detects both acute and chronic infarcts with a
18
Cardiomyopathy
sensitivity approaching that of serum assays for cardiac enzymes. Unlike cardiac enzymes which are cleared from the blood in a few days, however, ceMRI provides a permanent record of infarction, localizes the infarct to a specific coronary artery territory, and can be combined with cine MRI to document the effect of the infarct on wall motion with perfect registration. In addition, preliminary results suggest that hyperenhancement may be specific for ischemic injury. The applicant studied patients with non-ischemic cardiomyopathy determined by coronary angiography. Despite profound ventricular dysfunction, hyperenhancement was not observed in these patients. Detailed analysis of the data from patients with ischemic and non-ischemic cardiomyopathy strongly suggested that, for patients with ischemic disease, the presence or absence of irreversible injury. To investigate this further, the applicants examined wall motion in patients before and after revascularization by CABG or PTCA. For the 804 segments with a baseline wall motion abnormality, the likelihood of recovery of wall motion after revascularization was strongly predicted by the presence or absence of hyperenhancement. These preliminary data underscore that ceMRI in combination with cine MRI can provide detailed diagnostic information. The applicants propose to establish the sensitivity of ceMRI to detect chronic infarction in patients (Aim 1), to test the hypothesis that recovery of wall motion following revascularization is predicted by ceMRI (Aim 2), and determine if ceMRI can distinguish between patients with ischemic and non-ischemic cardiomyopathy (Aim3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CHEMISTRY Principal Investigator & Institution: Han, Xianlin; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Numerous animal studies have demonstrated that the diabetic states induces a fatty acid-based metabolic dysfunction which has complex effects on multiple endorgan systems. Both accelerated atherosclerosis and diabetic cardiomyopathy are the major etiologic agents in the excessive cardiovascular mortality and morbidity present in diabetic patients. A central theme in diabetic cardiovascular disease is the dysfunctional accumulation of lipids in multiple critical cell types. The proposed research in the component projects focuses on the role of alterations in peroxisomal regulatory proteins (e.g., peroxisomal phospholipases) and proliferative elements (e.g., PPARalpha and PPARgamma) which accelerate atherosclerosis and predispose critical cells in the cardiovascular system to maladaptive metabolic alterations. Core A of the program project embodies five major technical advances either made in our early research or developed in the current chemistry Core. Provision of lipid-analytical, synthetic, and proteomic services to the component projects will facilitate the costeffective accrual of vital scientific information for the elucidation of the molecular mechanisms underlying altered lipid metabolism in the diabetic state. The Core will offer a wide variety of state-of-the-art analytic (mass spectrometry, evaporative light scattering detection (ELSD), fluorescence spectrometry, quantitative PCR) and synthetic (chiral BEL, fluorescence probe for real-time PLA2 assays) expertise. Specifically Core A will perform: 1) analysis of polar and neutral lipid individual molecular species including free fatty acids, triacylglycerides, cholesterol, acylcarnitines, and all types of phospholipids from biological sources using state-of-the-art ESI/MS and ELSD with sensitivity at the subpicomole to picomole range; 2) proteins sequencing and protein post- translational modification determinations utilizing LC/MC (proteomics); 3) the synthesis of the iPA2 suicide inhibitor (i.e., BEL) and its resoled enantiomers which
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selectively inhibit iPA2beta dn iPLA2gamma; 4) real-time PLA2 activity assays utilizing novel fluorescence substrates we have developed; and 5) quantitative PCR utilizing Taqman methodology. As it has done during the current grant interval, the Core will continue to provide methodologic advances to facilitate the study of lipid and protein alterations in the diabetic state (see Progress Report). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINES CARDIOMYOPATHY
AND
LV
RECOVERY
IN
RECENT
ONSET
Principal Investigator & Institution: Mcnamara, Dennis M.; Director, Heart Failure Research Program; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant): For patients presenting with the recent onset of primary dilated cardiomyopathy, the presence of myocardial inflammation may suggest a potentially self limited and reversible process, and patients with acute "myocarditis" may actually have a better probability of left ventricular recovery than those with more chronic disease. The poor sensitivity of endomyocardial biopsy has limited its clinical utility, and circulating plasma cytokines are potentially more sensitive indicators of a reversible myocardial inflammatory process. This proposal will investigate the hypothesis that the assessment of plasma cytokines in recent onset dilated cardiomyopathy, can help to prospectively delineate patients with greater likelihood of myocardial recovery. Specific Aim 1 will assess the correlation of baseline plasma cytokine levels (TNFa, TNF receptors, and IL-6) with echocardiographic measures of left ventricular systolic and diastolic function. The study will enroll 120 patients with recent onset idiopathic dilated cardiomyopathy or myocarditis with an LVEF less than or equal to 0.40. This will evaluate the hypothesis that plasma cytokines in recent onset cardiomyopathy are markers of cardiac inflammation and will correlate with more profound perturbations of myocardial function. Specific Aim 2 will evaluate the hypothesis that patients with more active myocardial inflammation (higher plasma TNFa) upon presentation, are more likely to have significant recovery of left ventricular systolic function at 12 month follow up. Echocardiographic assessment will be repeated at 6 and 12 months after entry. In addition we will evaluate the hypothesis that patients with higher plasma IL-6 levels will have a poorer event free survival during subsequent follow up. Specific Aim 3 will explore the hypothesis that polymorphisms of cytokine genes, in particular those in the TNFa and IL-6 promoters, will effect levels of their respective mediators, and will subsequently influence clinical outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOSKELETAL INTERACTIONS OF DYSTROPHIN Principal Investigator & Institution: Ervasti, James M.; Professor; Physiology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-JUL-1994; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract): The objective of this project is to determine the cytoskeletal interactions of the dystrophin-glycoprotein complex in the skeletal muscle to understand how its absence or abnormality leads to Duchenne (DMD) and Becker (BMD) muscular dystrophies and some forms of cardiomyopathy. Rather than just simply serving to anchor its associated glycoprotein complex to the cortical actin, our previous studies lead us to hypothesize that dystrophin also plays an
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important role in stabilizing the cortical cytoskeleton through an extended lateral association with actin filaments. We further hypothesize that the dystrophin homologue utrophin is missing an actin binding suite important for F-actin stabilization. These hypotheses will be tested, both in vitro and in vivo, through the pursuit of 3 complementary specific aims. The F-actin binding properties of full-length and truncated forms of recombinant dystrophin and utrophin will be measured by established biochemical and spectroscopic procedures (Aim 1). Completion of this aim will yield the first direct structure/function comparison for dystrophin and utrophin up-regulation to effectively compensate for dystrophin deficiency. Recombinant dystrophin/utrophin will be visualized alone and in complex with actin filaments using electron microscopy combined with three-dimensional reconstruction techniques (Aim 2). These studies will yield important new information about the shape, dimensions and flexibility of dystrophin and utrophin and will independently determine how much (and which sub-domains) of dystrophin lie in close apposition with F-actin. Analysis by three-dimensional reconstruction will also identify changes in actin monomer and filament structure that may lead to more stable association of other costameric proteins with F-actin. Finally, we will relate the in vitro features of the dystrophin/F-actin interaction with its role in stabilizing costomeric actin in vivo (Aim 3). Sarcolemmal membranes will be mechanically isolated from muscles of transgenic mdx mice expressing dystrophin constructs deleted in different domains and the status of costameric actin determined by confocal microscopy. We will also determine whether the absence of dystrophin results in an unstable sarcolemmal association of other costameric actin binding proteins. Completion of these aims will result in a highly detailed and integrated understanding of dystrophin's role in stabilizing the muscle membrane cytoskeleton through its interaction with cortical actin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT AND MAINTENANCE OF LENS TRANSPARENCY Principal Investigator & Institution: Clark, John I.; Professor and Acting Chairman; Biological Structure; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-JUN-1982; Project End 31-JUL-2008 Summary: (provided by applicant): Human alphaBeta crystallin is the archetype for small heat shock proteins, sHSP, that are involved in protein aggregation and filament assembly diseases including cataracts, neurodegeneration, cardiomyopathy and desmin related myopathy. Interactions between alphaBeta crystallin are necessary for normal filament assembly and organization of crystallins in lens cells. In aim 1, characterization of the interactive sites for subunit assembly, for cytoskeletal proteins and for target peptides on human alphaBeta crystallin, the peptide sequences of the interactive domains on human alphaBeta crystallin will be identified using a protein multipin arrays. The affinities between the interactive domains will be quantified using surface plasmon resonance (SPR) and characterized functionally using in vitro and in vivo assays for chaperone activity. The results are expected to provide new information on the structural basis for the assembly of sHSP subunits to functional complexes and for their interaction with chaperone target proteins and with cellular filaments and cytoskeletal elements. In aim 2, in vivo evaluation of retina - lens relationships that may influence development and maintenance of lens transparency in transgenic mice, the historical hypothesis that a lens - retina relationship is important for normal development of lens cell transparency will be studied. Electroretinograms (ERG) and digital slit lamp recordings of opacity in selected animal models will quantify
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transparency with retinal function during the development of the lens and during loss of transparency in models for cataract formation. Lastly, the hypothesis that lens cytoskeleton provides a scaffold for development and maintenance of transparent lens fiber structure will be investigated in aim 3, observe the cellular organization of major structural proteins in differentiating lens fibers during development of lens transparency and during loss of transparency in the selenite rat and in selected transgenic mouse models using confocal microscopy and electron microscopy (EM). The patterns and distribution of the cytoskeleton and crystallins during differentiation of transparent lens fibers will be investigated using electron microscopy and confocal immunocytochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF DIABETIC CARDIOMYOPATHY IN GLUT4 +/MICE Principal Investigator & Institution: Charron, Maureen J.; Professor of Biochemistry; Biochemistry; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 31-MAR-2005 Summary: (Scanned from the applicant's abstract) Mice with a single knockout allele of GLUT4(+/-) on a low fat diet develop type II diabetes including hyperinsulinemia, hyperglycemia, hyperleptinemia, mild hypertension, cardiomyopathy and liver steatosis with age. These pathologies occur independent of obesity, dyslipidemia, pancreatic failure and hepatic insulin resistance. We propose to conduct the first in vivo longitudinal study which examines critical molecular/metabolic/energetic alterations leading to diabetic cardiomyopathy. This addresses the important interplay between whole body metabolism and circulating factors that regulate cellular processes which result in end organ pathology. The central hypothesis is global reduction of GLUT4 expression and/or function leads to alterations in cardiac insulin action, glucose metabolism and energetics mediated by reductions in the activity of PPARgamma and Akt/PKB which result in altered contractile function and diabetic cardiomyopathy. Altered substrate use with increased reliance upon fatty acid metabolism is associated with increased oxidative stress and mitochondrial uncoupling that result in diminished energy reserves. Insulin sensitizer treatment with BRL49653, a thiazolidinedione (TZD) that activates PPARg, will improve whole body glucose homeostasis and cardiac function through alterations in AktJPKB activity, substrate usage and expression of uncoupling protein (UCP) and glucose transporter (GLUT) genes/proteins. These studies will provide unique insight into molecular, metabolic, and morphologic alterations in GLUT4+/- hearts as mice progress to diabetes that should facilitate development of therapeutics to prevent and/or minimize diabetic cardiomyopathy in humans. To accomplish these goals we have four specific aims. Each aim will identify alterations in insulin action through Akt/PKB, GLUT4- and GLUTx1 translocation, substrate partitioning/trafficking, and GLUT and UCP2/3 gene/protein expression in hearts of GLUT4+/- and control mice. Molecular and cellular analyses will be correlated with morphologic and hemodynamic changes in heart and alterations in whole body glucose homeostasis and circulating serum factors (e.g. leptin, insulin, T3/T4, glucose, free fatty acids) as mice progress from normal (N/N) to prediabetic (N/H) to overt diabetic (H/H) phenotypes. Effects of short term treatment with the TZD BRL49653 (PPARg agonist) on these parameters will be defined before significant alterations in body weight or adiposity can be measured. The latter studies will determine the mechanism of action of TZDs in the heart and may reveal novel therapeutic targets and applications.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIABETIC ALTERATIONS OF CARDIAC METABOLISM AND FUNCTION Principal Investigator & Institution: Chatham, John C.; Associate Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract): Diabetes is associated with an increased risk of heart failure, independently of other risk factors. There is also increased evidence of diabetic cardiomyopathy as an independent entity. The pi and his collaborators have shown a direct link between cardiac dysfunction and metabolic impairments in myocardial metabolism. Evidence from the investigator's laboratory strongly suggests that the provision of substrates for energy production is impaired at the level of the mitochondrion. Based on these observations, the PI has elaborated the hypothesis that this is indeed the case. Specifically, the investigator proposes that this is manifested in alterations at multiple sites such as lactate uptake and oxidation, fatty acid entry and oxidation, pyruvate oxidation and anaplerosis and citrate cataplerosis. These changes then lead to clinical problems under conditions of increased demand when energy provision cannot match utilization. The tools the PI proposes to use include: 1) The spontaneously diabetic BB/Wor rat and the diabetes-resistant controls. 2) The perfused working heart model with measurement of contractile efficiency, which has now been implemented in the laboratory. 3) Perfusion with buffer containing RBC's to increase oxygen carrying capacity and decrease perfusion rate so that a-v differences can be measured. Simultaneous use of C13 labeled substrates, and in situ and high resolution NMR spectroscopy and GCMS in perfusate and extracted myocardial samples to determine metabolite flux rates using isotopomer analyses. Complementary measurements of enzyme activities, transporters (lactate, fatty acid) and their expression in the myocardial tissue extracts. Finally, linkage of all of the above data using metabolic control analysis to establish the principal control points. It is underlined that the understanding of the relationship between cardiac function and metabolism is essential in instituting appropriate treatment so that therapeutic interventions to improve contractile function do not exacerbate the metabolic problems, ultimately increasing tissue injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIABETIC CARDIOMYOPATHY: TGFBETA ACTIVATION AND FIBROSIS Principal Investigator & Institution: Murphy-Ullrich, Joanne E.; Professor; Pathology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: (provided by applicant): Diabetic cardiomyopathy, characterized by myocyte hypertrophy and interstitial fibrosis, is a potentially life-threatening complication resulting from lack of glycemic control. Hypertension associated with diabetes increases disease severity. TGF-beta is the primary effector of fibrosis in response to hyperglycemia. Bioactivation of latent TGF-beta is a major regulatory step in controlling TGF-beta and a logical point for therapeutic intervention. Yet, regulation of TGF-beta bioactivity in these diseases is not well understood. The platelet/matrix protein, thrombospondin l (TSP 1), is a physiologic regulator of latent TGF-beta activation. TSP 1 regulates glucose-stimulated increases in TGF-beta bioactivity and matrix protein
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synthesis in mesangial cells. TSP-dependent TGF-beta activation is also important for the diabetic myocardium, since high glucose stimulates TSP1 and TGF-beta bioactivity in rat cardiac fibroblasts and increases in TGF-beta bioactivity are blocked with TSP antagonist peptides. Similarly, data show that angiotensin II (Ang 11)-stimulates increased TSP 1 expression and TGF-beta bioactivity that can be blocked by addition of the antagonist peptides. Both glucose and Ang II up-regulate TSP 1 expression, potentially through modulation of PKC and nitric oxide (NO). These data support the hypothesis that glucose-mediated modulation of PKC, NO, ROS, and Ang II are involved in the regulation of TSP1 expression, leading to latent TGF-beta activation, matrix protein synthesis, and myocardial fibrosis. In this proposal, we will use a cultured cardiac fibroblast system to determine 1) the interrelationships between glucose, PKC activity, and oxidative balance in regulation of TSP 1 expression, TGF-beta bioactivity, and matrix protein synthesis and; 2) the role of Ang II in regulation of TSP 1dependent TGF-beta activation and its relation to glucose stimulation. In addition, rats with diabetes (streptozotocin) and hypertensive diabetes will be used to determine 3) whether peptide antagonists of TSP-mediated TGF-beta activation ameliorate diabetic myocardial fibrosis under normo- and hypertensive conditions. These studies will further our understanding of how TGF-beta is regulated in diabetes and hypertension, and will potentially identify new strategies for therapeutically attenuating myocardial fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL EFFECTS OF SR CA2+ RELEASE IN CARDIAC MYOCYTES Principal Investigator & Institution: Wasserstrom, J A.; Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): One of the most serious secondary effects of alcohol abuse is the development of specific alcohol-induced cardiomyopathies which often lead to congestive heart failure. Previous findings suggest that one of the mechanisms underlying reduced cardiac function by ethanol (EtOH) may involve the direct suppression of cardiac excitation-contraction (E-C) coupling. Interestingly, this direct effect does not appear to involve alterations in the trigger for cardiac contraction (via Ltype Ca 2+ current) raising the possibility that the primary negative inotropic effects of EtOH might reside in an altered response to that trigger. The goal of this project is to investigate how EtOH affects Ca2+ release from internal stores in the sarcoplasmic reticulum (SR) during the cardiac cycle. This will be accomplished through measurement of Ca 2+ sparks, which are thought to represent the fundamental Ca 2+ release units responsible for contraction. The Specific Aims of this project are: 1) to determine if the cardiodepressant effects of EtOH occur as the result of a direct suppression of SR Ca 2+ release; and 2) to investigate whether or not these changes in SR Ca 2+ release contribute to the depression in cardiac function that occurs in a chronic model of alcohol-induced cardiomyopathy. Ca 2+ sparks will be measured in rat ventricular myocytes with the Ca2+-sensitive fluorescent indicator fluo-4 using laser scanning confocal microscopy in combination with whole cell voltage clamp techniques. Some experiments will be performed in saponin-permeabilized myocytes exposed to different cytosolic Ca2+ concentrations in order to assess Ca 2+ sensitivity of Ca 2+ sparks activated purely by Ca 2+ in the absence of functional sarcolemmal Ca 2+ current. These methodological approaches will allow the investigation of how EtOH affects SR Ca 2+ release that occurs both as a result of its normal trigger (L-type Ca 2+
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channels) and in response to the final common pathway for E-C coupling, direct activation by Ca 2+. In addition to the study of direct effects of EtOH on the physiological and biophysical processes responsible for SR Ca 2+ release, we will also correlate these changes in SR Ca 2+ signaling with the development of alcohol-induced cardiomyopathy in order to determine if the reduction of cardiac output at the whole organ level occurs as the result of a suppression of E-C coupling at the level of the SR. The results of this study will contribute to our understanding of the mechanisms by which EtOH interferes with SR Ca 2+ release and whether or not this mechanism involves the trigger for E-C coupling or the response to that trigger. More importantly, such information can then be applied to understanding how a reduction in SR function by EtOH might contribute to chronic suppression of overall cardiac function, leading to the development of cardiomyopathies and heart failure associated with long-term alcohol abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAMILIAL HYPERTROPHIC CARDIOMYOPATHY--SARCOMERIC DISEASE Principal Investigator & Institution: Warshaw, David M.; Professor and Chariman; Molecular Physiol & Biophysics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 18-FEB-1999; Project End 31-JAN-2004 Summary: Familial hypertrophic cardiomyopathy (FHC), an inherited disease with a high incidence of premature death due to cardiac failure, has its genetic loci in the contractile proteins in the heart. Thus, FHC may be a disease of the sarcomere, muscle's most basic contractile unit. In the sarcomere, myosin, a molecular motor, interacts with actin to generate the power of the heart. This Program Project (3 projects and 3 cores) focuses on mutations to myosin and the actin regulatory proteins, troponinT, and tropomyosin. Using state-of-the-art techniques, we will characterize FHC from the mechanics of the whole heart down the molecular mechanics of a single contractile protein, to assess how structural alterations to these proteins affect the mechanical properties of the sarcomere, the muscle fiber, and the whole heart. Project #1 will study the mechanical properties of the whole heart and papillary muscles obtained from transgenic mice with mutations in either myosin, troponinT, or alpha- tropomyosin. Project #2 will genetically engineer FHC mutations into myosin using an in vitro protein expression system. Project #2 will biochemically characterize these proteins, while project #3 will use the laser optical trap to assess the force and motion generating capacity of these mutants at the single molecule level. All projects use the Analytical and Modeling Core (Unit B) for expertise in data collection, analysis, and modeling. In addition, the Mouse Production and Ventricular Function Core (Unit C) will generate mice with FHC mutant hearts that will be studied at all anatomical levels by the various projects. In addition, this Core will also characterize the in vivo ventricular performance of the hearts within the transgenic mice. The long-term goals are: 1) to utilize FHCrelated point mutations as a means of identifying key structural domains within the mutant sarcomeric proteins and to determine how these domains relate to the protein's molecular function; 2) to understand how point mutations in contractile proteins compromise sarcomere function, and how these mutations, in turn, may trigger cardiac hypertrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FRIEDRIECHS ATAXIA, MITOCHONDRIA AND CELL DEATH Principal Investigator & Institution: Cortopassi, Gino A.; Associate Professor; Vet Molecular Biosciences; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAR-2004 Summary: (adapted from Investigator's abstract) The human disease Friedreich's ataxia (FA) causes progressive age-related neurodegeneration and cardiomyopathy associated with increased mitochondrial oxidative stress and damage. This human cellular model allows intensive experimental testing of cause and effect relationships between increased mitochondrial reactive oxygen species (ROS), and downstream molecular damage, pathophysiology and cell death. Specific aims of this study are: (1) to characterize the type of increased ROS that occurs in FA, (2) to quantify the contribution of increased ROS to damage of mitochondrial lipids, mtDNA, and proteins, (3) to quantify the effects of this damage on the major possible mitochondrial physiological endpoints, and (4) to rescue phenotypes by inhibitors specific for each step in the hypothetical chain, and test its validity at the biochemical and cellular level and in knockout organisms constructed in Aim 5. These molecular targets of mitochondrial and oxidative damage in human cells, once identified and validated as pathophysiologically relevant will serve as targets for further analysis in the more complex situation of aging in humans and animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL MR IN ISCHEMIC CARDIOMYOPATHY Principal Investigator & Institution: Grayburn, Paul A.; Professor; Baylor Research Institute 3434 Live Oak St, Ste 125 Dallas, Tx 75204 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Functional mitral regurgitation (MR) is a common complication of ischemic heart disease. Two large clinical trials confirmed an adverse effect of functional MR on survival after a heart attack. However, studies in heart failure are small and mainly limited to patients with nonischemic cardiomyopathy. Recent animal studies have challenged the traditional concept that functional MR is a consequence of mitral annular dilation, instead suggesting that functional MR is due to leaflet tethering by outward expansion of the left ventricular wall (i.e. LV remodeling). This has critical implications regarding the correct surgical approach to correcting functional MR. TO date, no large prospective studies have examined the mechanism(s) of functional MR in ischemic cardiomyopathy, nor has the interaction between mechanism and prognosis been explored. This is a crucial knowledge gap because 1) 70% of heart failure cases are caused by ischemic heart disease, and 2) functional MR occurs in around 60% of patients with ischemic cardiomyopathy. This proposal aims to fill these gaps by defining the mechanism(s) of functional MR by transesophageal echocardiography in a large clinical trial of patients with ischemic cardiomyopathy. The following specific aims will be addressed: Aim 1: To define the mechanism(s) of functional MR in ischemic cardiomyopathyAim 2: To define the effect of therapy on mechanism and severity of functional MRAim 3: To evaluate the effect of functional MR on prognosis is ischemic cardiomyopathyAim 4: To evaluate the effect of myocardial viability on functional MR and its response to treatment We propose to accomplish these aims as a ancillary study to the Surgical Treatment of Ischemic Heart Failure (STICH) Trial. The STICH Trial will compare surgical revascularization versus medical therapy for treatment of heart failure in 2800 patients with ischemic cardiomyopathy,
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and therefore affords a unique opportunity to investigate the mechanism(s) of functional MR. Despite its known clinical utility of assessing the mechanism and severity of MR, TEE is not currently included in STICH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: G PROTEIN COUPLING OF LIPID METABOLISM IN DIABETIC HEART Principal Investigator & Institution: Muslin, Anthony J.; Professor of Internal Medicine, Cell Bio; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Both Type I and Type II diabetes are accompanied by a profound switch in myocardial substrate utilization form one which utilizes nearly equal amounts of glucose and fatty acid to a state which predominantly employs FA for substrate. Gproteins in he heart have important effects in mediated the electrical and contractile proteins for myocardium which depend, in part, on an appropriate membrane microenvironment to carry out their specific functions. In the diabetic state profound changes in lipid synthesis occur including alterations in phosphatidylinositol (to which Gq is coupled through phospholipase C leading to IP3 generation) and in the content of plasmalogen which have dramatic effects on membrane fluidity and dynamics. During the last fie years substantial evidence has been accrued demonstrating the altered activity and function of the G-protein axis in diabetic myocardium. These include decreases in beta adrenergic receptor number, increases in Gq-protein mass, altered Gprotein receptor-effector coupling, increases in PKCepsilon activity and changes in intracellular calcium ion homeostasis. Thus, it seems likely that altered G signaling contributes to, or underlies the propagation of the pathophysiology manifest in the diabetic heart. The primary hypothesis of Project 4 is that diabetic cardiomyopathy develops as a result of abnormal stimulation of Gq and Gi protein- mediated signaling pathways that leads to alterations in intracellular phospholipases, peroxisomal lipid metabolism and lipid second messenger generation. In order to test this model of diabetic cardiomyopathy we will evaluate the functional and biochemical sequelae of increased or decreased G protein-mediated signal transduction in diabetic murine myocardium. In particular, we will determine whether reduced Gq and Gi signaling in the heart inhibits the development of cardiomyopathy in diabetic mice. G protein signaling will be attenuated by use of RGS4, a GTPase activating protein for Gq and Gi family members. The identify of the specific G protein involved will be determined by targeted disruption of individual Galpha subunit genes. In addition, we will evaluate whether increased Gq signaling potentiates the development of diabetic cardiomyopathy. Furthermore, we will determine whether Gq or Gi signal transduction in heart promotes PLA2 activation and changes in lipid metabolism. Finally, we will examine the transduction in heart promotes PLA2 activation and changes in lipid metabolism. Finally, we will examine the physiological role of the sarcolemmal phospholipase cPLA2gamma, in the pathogenesis of diabetic cardiomyopathy and we will determine whether G protein-mediated signaling regulates activation of this phospholipase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY Principal Investigator & Institution: Kimonis, Virginia E.; Children's Hospital (Boston) Boston, Ma 021155737
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Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2004 Summary: (Taken from the application): Limb-Girdle Muscular Dystrophy (LGMD) encompasses a clinically diverse group of disorders characterized by proximal muscle weakness first affecting the hip and shoulder girdle elevated creatinine kinase values, and non-specific changes in the muscle biopsy. In addition to clinical heterogeneity within the LGMD category, genetic heterogeneity is indicated by the existence of dominant and recessive forms. We have identified a large family with autosomal dominant LGMD and early onset Paget disease of bone (PDB). These individuals have bone pain in the hips, shoulders and back from the Paget disease. Individuals eventually become bed bound and die prematurely from progressive muscle weakness +/cardiomyopathy in their forties to sixties. Laboratory investigation indicates elevated alkaline phosphatase levels in affected individuals. CPK is normal to mildly elevated. Muscle biopsy of the oldest affected male revealed non-specific changes and vacuolated fibers. Preliminary molecular analysis excluded linkage to the known loci for the autosomal dominant and recessive forms as well as 2 loci for autosomal dominant PDB and 6 loci for cardiomyopathy. Exclusion of the candidate loci prompted a genomewide scan of 39 family members (9 affected, 24 unaffected, 6 spouses} with 402 polymorphic microsatellite markers (Marshfield Genotyping Services). The disease locus was linked to chromosome 9p21-q21 with marker D9S301 (max LOD=3.64), thus supporting our hypothesis that this family displays a genetically distinct form of LimbGirdle-Muscular-Dystrophy associated with Paget disease of bone and cardiomyopathy. Subsequent haplotype analysis with a high density of microsatellite markers flanking D9S301 refined the disease locus to a 3.76 cM region on chromosome 9p21-13.2. This region excludes the IBM2 locus for autosomal recessive vacuolar myopathy. Two candidate genes mapped to the critical region, NDUFB6 and IL-11RA, are being examined for disease-associated mutations. NDUFB6 encodes a subunit of Complex I of the mitochondrial respiratory chain and the IL11RA gene product influences proliferation and differentiation of skeletogenic progenitor cells. Identification of the genes involved in the LGMDs has led to the elucidation of an entire family of proteins that function in the dystrophin-glycoprotein complex. and a basis for understanding the pathophysiology of this complex. Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR CHRONIC HEART FAILURE Principal Investigator & Institution: Soltesz, Edward G.; Surgery; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 23-DEC-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Congestive heart failure (CHF) is a growing clinical problem nationwide. Despite advances in traditional approaches to its treatment, CHF remains a leading cause of morbidity and mortality. A key abnormality at the cellular level in failing hearts is a defect in sarcoplasmic reticulum (SR) function which is associated with abnormal intracellular calcium handing. Failing hearts from humans and animal models have demonstrated a decrease in the expression and activity of the SR Ca2+ATPase (SERCA2a). Recently, we have shown that restoring depressed levels of SERCA2a restores contractility and normalizes intracellular calcium cycling in a rodent model of CHF. We are now extending our experiments to a porcine model of ischemic cardiomyopathy with clinical-grade vectors and delivery systems. Specifically, we will investigate whether (1) overexpression of SERCA2a can improve hemodynamic function
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in a porcine model of ischemic cardiomyopathy, and (2) long-term overexpression of SERCA2a will induce ventricular and metabolic remodeling without adversely effecting enerqetics in a porcine model of ischemic cardiomyopathy. To answer these questions, we will utilize a porcine model of heart failure where there is depressed LV function and SERCA2a protein levels to examine the response to overexpressing levels of SERCA2a through gene therapy. We will measure hemodynamic function in these animals before and after the delivery of the gene as well as assess the level of SERCA2a expression. We expect to show that gene transfer of SERCA2a to failing porcine hearts will rescue contractility and lead to ventricular and metabolic remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENES TRANSGENICS
THAT
CONTROL
CARDIAC
CELL
NUMBER--EIA
Principal Investigator & Institution: Field, Loren J.; Professor; Medicine; Indiana UnivPurdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Clinical recovery from myocardial infarction is thwarted, in part, by inability of surviving ventricular myocytes to reconstitute functional cardiac mass through a corresponding, compensatory increase in cell number. This highlights the limited capacity to restore cardiac mass by hypertrophy alone, and deleterious effects associated with hypertrophy that further impair survival. On-going myocyte loss also appears likely as an eventual contributor to end-stage heart failure. Conventional therapies for heart failure are aimed at rescuing jeopardized myocardium, optimizing mechanical load, or augmenting the mechanical performance of surviving myocytes. In principle, strategies to increase the number of functional ventricular myocytes have potential for a clinical benefit. (This theme is among the highest priorities expressed by the NHLBI Special Emphasis Panel on Heart Failure Research and the present RFA.) Three complementary, gene-based approaches have been brought to bear on the problem of cardiac cell number in this Collaborative RO1-transdifferentiation, manipulation of cell cycle constraints, and interference with pathways for programmed cell death (apoptosis). Viral delivery of cardiogenic transcription factors and upstream cardiogenic signals will be explored by Dr. Robert Schwartz. Drs. Michael Schneider and Loren Field will use gain-and loss-of- function mutations to dissect the "post-mitotic" phenotype in vivo, and will use co-precipitation or interaction cloning to isolate the endogenous cardiac proteins affecting cell cycle exit. Dr. Konstantin Galaktionov, an expert on Cdc25, will study molecular regulators of the G2/M transition, a second checkpoint that must be overcome for cell number to be increased. Mechanisms and countermeasures for cardiac apoptosis will be tested by Dr. Doug Mann, with emphasis on dilated cardiomyopathy triggered by overexpression of tumor necrosis factor alpha, and on investigations of human myocardium. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF DILATED CARDIOMYOPATHY Principal Investigator & Institution: Jha, Sanjay; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 09-JUL-2001; Project End 31-MAY-2007 Summary: (provided by applicant) Dilated cardiornyopathy (DCN4) is a disease characterized by cardiac chamber dilation and deterioration of systolic function. it accounts for 10,000 deaths annually In the United States, and is an etiologically
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heterogeneous disorder with a strong genetic component. The central goals of this project are to identify genes involved in the pathogenesis of DCM, and to obtain the necessary training in cardiovascular genetics over a proposed five year period, to prepare for a career as an independent investigator. Research will focus on four specific alms critical for identification of genes involved in DCM pathogenesis. 1) Ascertainment and phenotypic characterization of individuals and families with DCM. Families and sporadic cases suitable for genetic analyses will be identified from congestive heart failure and transplant clinics at1he University of Utah and University of Pennsylvania system hospitals. 2) Identification of new DCM loci using genetic linkage analysis in large kindreds. Genome-wide linkage scans using highly polymorphic markers will be performed on large DCM families that do not link to known loci. 3) Positional cloning of a DCM gene on chromosome 3p. The critical genetic interval for a DCM locus previously identified by this laboratory will be cloned. Candidate genes identified in the region will be screened for mutations that co-segregate with the disease phenotype in the family where linkage was established. 4) Identification and mutation screening of candidate genes in familial and sporadic DCM populations. We will identify genes, which on the basis of physiologic rationale, may play central roles in DCM pathogenesis. The candidate genes will be screened for mutations in our patient population. The principle investigator has completed training in clinical cardiology. This application now proposes to build on his research background in Drosophila developmental genetics obtained in the laboratory of Dr. David Hogness. Over a five year period, an expertise in genetic approaches to understanding the molecular pathogenesis of dilated cardlomyopathy will be developed. The candidate's sponsor, Dr. Mark Keating, is a recognized leader in the field of cardiovascular genetics. An advisory committee consisting of two other senior scientists, Dr. Mark Leppert and Dr. Michael Parmacek, will provide additional scientific and career guidance. The Department of Human Genetics at the University of Utah is a center for the study of genetic diseases and provides an outstanding environment for the candidate to develop into an independent investigator. (End of Abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS STUDIES OF FAMILIAL DILATED CARDIOMYOPATHY Principal Investigator & Institution: Mcnally, Elizabeth M.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Many etiologies lead to the development of dilated cardiomyopathy. Idiopathic dilated cardiomyopathy arises from intrinsic muscle disease in the presence of normal coronary arteries and the absence of a clear toxic or immunologic insult. Approximately 30 percent of idiopathic dilated cardiomyopathy patients have first degree relatives that also show evidence of cardiac dilatation with or without symptoms of congestive heart failure. Supporting this, genetic loci have been significantly associated with familial dilated cardiomyopathy (FDC). Positional cloning efforts are underway to increase our understanding of the molecular mechanisms that underlie familial dilated cardiomyopathy. Through genetic linkage analysis, we have identified a region of chromosome 6q23 that is associated with dilated cardiomyopathy, conduction system disease that produces progressive atrio-ventricular block and a mild, adult onset, slowly progressive muscular dystrophy. We have constructed a physical map of this region of chromosome 6 and evaluation of candidate genes is underway. We have also discovered a second region, chromosome 2q22, that is associated with dilated cardiomyopathy and ventricular arrhythmias. We propose to refine the genetic interval,
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identify candidate genes and, through mutation analysis, identify the gene responsible for chromosome 2-associated FDC. The FDC-gene product will be studied for expression patterns in both normal and diseased tissue. The murine homolog of the FDC-gene will be determined. We will also establish a clinical and DNA database of dilated cardiomyopathy patients. This database will be used to determine the role of certain mutations in the development of the cardiomyopathic process. While genetic heterogeneity is present in FDC, the study of genes responsible for this disorder will reveal whether multiple cellular mechanism lead to cardiomyopathy. Additionally, in families with dilated cardiomyopathy, we find a prodrome of arrhythmias prior to the onset of cardiac dilatation and congestive heart failure. By developing genetic markers, we will identify those at risk for arrhythmia and most like to benefit from pacemaker and/or implantable defibrillator treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOMICS OF CARDIOVASCULAR DEVELOPMENT, ADAPTION Principal Investigator & Institution: Izumo, Seigo; Director of Cardiovascular Research; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2004 Summary: The goal of this PGA is to begin linking genes to function, dysfunction and structural abnormalities of the cardiovascular system caused by clinically relevant, genetic and environmental stimuli. The principal biological theme to be pursued is how the transcriptional network of the cardiovascular system responds to genetic and environmental stresses to maintain normal function and structure, and how this network is altered in disease. In Specific Aim 1, the investigators will take a multidisciplinary approach combining well-defined mouse models of cardiomyopathy and vasculopathy with an integrated analysis of physiology, pathology, and RNA expression profiling to search for prototypical patterns of gene expression in response to various genetic and non-genetic perturbations. In Specific Aim 2, the investigators will perform transcriptional profiling using human myocardium and vascular tissues obtained at the time of cardiac transplant or biopsy, and compare the transcriptional profile data with those of various mouse models. In Specific Aim 3, the investigators will screen for mutations that cause cardiovascular malformations with particular emphasis on hypertrophic cardiomyopathy, dilated cardiomyopathy, and selected sets of patients with congenital heart disease. In Specific Aim 4, the investigators will examine 200 candidate genes, identified by the mouse and human expression studies, in 2093 individuals drawn from the Framingham Heart Study. In these studies, a single nucleotide DNA polymorphism analysis (SNP) will be correlated with echocardiographic evidence of left ventricle mass, ventricular function, cardiac chamber size and aortic root size. The data generated by all of the above studies will be analyzed by state-of-the-art informatics to search for logics for common as well as disease specific pathways. The data will be extensively annotated and made freely available to the scientific community through the interactive website. In summary, this PGA will generate a high quality, comprehensive data set for the functional genomics of structural and functional adaptation of the cardiovascular system by integrating expression data from animal models and human tissue samples, mutation screening of candidate genes in patients, and DNA polymorphisms in a well characterized general population. Such a data set will serve as a benchmark for future basic, clinical and pharmacogenomic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GI CARDIOPROTECTION
SIGNALING
IN
CARDIOMYOPATHY
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Principal Investigator & Institution: Baker, Anthony J.; Associate Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): In humans, chronically increased signaling through Gi-coupled receptors is associated with congestive heart failure (CHF) caused by idiopathic dilated cardiomyopathy or ischemic cardiomyopathy following myocardial infarction. However, the mechanisms responsible are unclear. Our working hypothesis is that chronically increased Gi signaling causes impaired excitation-contraction (ec) coupling. To test this hypothesis we will combine physiological measurements of cardiac muscle function with a novel transgenic mouse model in which a modified Gicoupled receptor (Ro1) is targeted to the heart. Expression of Ro1 is regulated by a tetracycline-controlled expression system (tet-system). We have recently shown that chronic Ro1 expression causes CHF and major abnormalities of Ca2+ transients and contraction. In contrast, acute Ro1 expression causes significant protection against ischemia/reperfusion injury, suggesting a dual role for increased Gi signaling in cardioprotection and disease. For this proposal we will determine the ec-coupling mechanisms and Gi signaling mechanisms involved in CHF and cardioprotection. Using single myocytes, cardiac trabeculae, and Langendorff perfused mouse hearts, we will determine the effect of Ro1 expression on Ca2+ transients and determine the mechanisms responsible by localizing abnormalities to specific Ca2+ handling processes. We will determine the effect of Ro1 expression on Ca2+-responsiveness and determine the mechanisms responsible by localizing abnormalities to specific contractile and regulatory proteins. Using the tet-system to turn off Ro1 expression after induction of CHF, we will determine the extent to which ec-coupling abnormalities are reversible. To elucidate signaling mechanisms, we will determine which of the major Gi pathways in the heart (Gi2 and Gi3) are involved; and whether signaling via the G protein alpha subunit and/or the betagamma dimer is involved. Using 3 model systems we will investigate Gi signaling effects (both deleterious and beneficial) and the ec-couplingand signaling mechanisms involved in: Aim 1. CHF caused by Ro1 expression; and recovery after terminating Ro1 expression. Aim 2. Acute Cardioprotection caused by Ro1 expression. Aim 3. CHF caused by ischemic cardiomyopathy. This research will provide new information on the dual role of Gi signaling in both heart failure and cardioprotection which may help identify new strategies to treat heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEMOCHROMATOSIS--EPIDEMIOLOGY MECHANISMS
AND
MOLECULAR
Principal Investigator & Institution: Beutler, Ernest N.; Chairman; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 28-APR-1998; Project End 31-MAR-2003 Summary: Hereditary hemochromatosis, a disease characterized by excess iron absorption leading to diabetes, cardiomyopathy, cirrhosis, and arthropathies, is arguably the most common clinically important genetic disorder of Europeans. Recently an HLA Class 1 gene, HLA-H was implicated in the etiology of this disease. Over 80 percent of hemochromatosis patients are homozygous for a C282Y mutation. Compound heterozygotes for C282Y and H62D appear to have an increased incidence of
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the disease. Sixty-thousand adults undergoing health care screening in the KaiserPermanente system will be screened, determining serum iron, iron binding capacity, ferritin, and mutations in HLA-H. Patients classified as having hemochromatosis will be phlebotomized to remove excess iron and to measure iron stores. This will establish the relationship between genotype, age, sex and clinical state, and size of iron stores, and provide data that can be used to guide programs screening for hemochromatosis. The hypotheses that heterozygotes are more susceptible to cardiovascular disease and other disorders and that they are benefited by being less susceptible to iron deficiency anemia will be tested using the extensive Kaiser-Permanente database. Hemochromatosis mutations, other than those known, will be sought. The HLA-H gene product may function like other HLA class 1 genes, binding peptides and associating with proteins such as beta2 microglobulin, calreticulin, transporter associated with antigen processing (TAP) and tapascin. Alternatively, it may function as a signaling molecule, like the Fc receptor. Determining how the HLA-H gene product functions should provide insight into its role in maintaining iron homeostasis. This will be done by using immunoprecipitating HLA-H containing complexes, determining HLA-H Fc receptor signaling properties and measuring the binding of peptides and other small molecules by HLA-H. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IGF-1 AND DIABETIC HEART Principal Investigator & Institution: Kajstura, Jan; Associate Professor; Medicine; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Verbatim from the application): The long-term objective of this application is to demonstrate that diabetic cardiomyopathy is characterized by myocyte death in which the local renin-angiotensin system (RAS) plays a primary critical role. Hyperglycemia induced by streptozotocin administration is anticipated to activate the transcription factor p53, respectively, by glycosylation and phosphorylation of the Cterminal of this protein. Enhanced p53 function may upregulate p53-dependent genes, such as bax, angiotensinogen and AT1 receptor, leading to the synthesis and secretion of Ang II and the sustained phosphorylation of the tumor suppressor. This vicious cycle may promote the chronic generation of Aug II and an increased susceptibility of cells to die. The induction of bax and the downregulation of bcl-2 by p53 may potentiate not only apoptosis, but also myocyte necrosis, resulting in restructuring of the ventricular wall, chamber dilation and impaired cardiac hemodynainics. Importantly, Aug Ilmediated responses may involve the formation of reactive oxygen species (ROS). ROS may constitute the ultimate signal in the activation of the cell death pathways. Insulinlike growth factor-i (IGF-1) opposes the consequences of p53 by phosphorylating its Nterminal and by stimulating transcription of mdm2 that may lead to the interaction of Mdzn2 and p53 proteins. Mdm2-p53 complexes attenuate p53 function, Ang II concentration, ROS generation, increase in Bax, decrease in Bcl-2 and, ultimately, cell death and ventricular remodeling. These hypotheses will be tested by performing studies in normal mice and transgenic mice overexpressing IGF-1 following the imposition of diabetes. In vivo studies will be complemented with in vitro experiments utilizing myocyte cultures infected with adenoviral vectors overexpressing human mutated p53 or human wild-type p53. These cells will be exposed to high concentration of glucose to establish a cause and effect relationship between triggers of cell death, i.e., glucose and Aug II, and factors preventing, i.e., mutated p53, and promoting, i.e., wild type p53, cell death mechanisms. These multiple analyses should allow to establish
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whether the myocyte RAS is fundamentally implicated in the development and progression of diabetic cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSULIN SIGNALING AND THE HEART IN DIABETES Principal Investigator & Institution: Abel, Evan D.; Assistant Professor; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The pathogenesis of cardiac dysfunction in diabetes is partially understood. Our goal is to determine the mechanisms by which reduced insulin signaling in cardiomyocytes and vascular endothelium contributes to the pathogenesis of diabetic cardiomyopathy. Our overall hypotheses are: (1) In diabetes, deficient or reduced insulin signaling in cardiomyocytes leads to an initial defect in glucose/pyruvate oxidation, and a secondary increase in fatty acid oxidation that leads to increased production of reactive oxygen species (ROS) that ultimately causes progressive mitochondrial injury. Increased fatty acid delivery to insulin resistant cardiomyocytes during diabetes will accelerate mitochondrial dysfunction. (2) In the heart the (acute and chronic) regulation of cardiac muscle substrate metabolism by insulin involves paracrine interactions between cardiomyocytes and other cells in the heart such as endothelial cells. Thus, impaired insulin signaling in these cells and in cardiomyocytes both contribute to altered cardiac metabolism and function. The consequences of these defects will be exaggerated when cardiac energy requirements are increased such as during left ventricular hypertrophy. Aim 1: will determine the mechanisms by which chronic deficiency of insulin signaling in cardiomyocytes impairs mitochondrial oxidative capacity and predisposes the heart to lipotoxic injury. Studies will be performed in mice with constitutive and inducible deletion of insulin signaling in cardiomyocytes. We will determine the mechanisms for changes in PDH activity, the mechanisms that lead to increased fatty acid utilization in these models and the role of increased ROS generation in precipitating mitochondrial dysfunction and lipotoxic cardiomyopathy. Aim 2: will determine the mechanisms by which non-myocyte cells in the heart modulate cardiomyocyte metabolism. We will determine if loss of insulin signaling in these compartments will accelerate or exacerbate the metabolic and functional impairment in hearts that lack insulin signaling in cardiomyocytes by studying hearts deprived of insulin signaling in endothelial cells and cardiomyocytes under basal conditions and following pressure overload hypertrophy. The role of nitric oxide in the paracrine regulation of myocardial metabolism by insulin will be determined. These studies will shed important insight into the regulation of cardiac function and metabolism by insulin and the role of impaired insulin signaling in the pathogenesis of diabetic cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTRINSIC PROBES OF SMOOTH MUSCLE MYOSIN DYMAMICS Principal Investigator & Institution: Berger, Christopher L.; Associate Professor; Molecular Physiol & Biophysics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: The ultimate goal of this proposal is to examine conformation changes at specific locations within smooth muscle myosin using intrinsic tryptophan fluorescence. Smooth muscle myosin constructs will be genetically engineered to contain a single
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tryptophan at the desired site of interest, which will provide a unique intrinsic fluorescence signal reporting local conformational and structural changes in response to nucleotide binding, ATP hydrolysis, and actin-binding. These experiments are complementary to the ongoing structural studies in the field, allowing us to explicitly test predictions about domain movements and structural arrangements during critical steps in the contractile cycle smooth muscle myosin. Thus we will be able to correlate structural changes in myosin with functional consequences, which relates directly to certain cardiovascular disease. For example, FHC (familial hypertrophic cardiomyopathy) is an inherited, often lethal disease caused by point mutations at key structures within myosin critical to its proper functioning as a molecular motor. We will be examining structural changes in myosin in regions of the molecule directly impacted by mutations that underlie FHC. This will lead to a better understanding of the disease, and thus to better treatment options as well. Therefore, this proposal offers a unique opportunity to critically test fundamental questions about the molecular mechanism of muscle contraction that have not been previously accessible by other spectroscopic probe studies, and the results will have important implications for serious disease states such as FHC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAGNETIC RESONANCE OF CARDIAC C13 FLUX & METABOLIC RATE Principal Investigator & Institution: Lewandowski, E Douglas.; Professor; Physiology and Biophysics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-AUG-1993; Project End 31-JUL-2008 Summary: (provided by applicant): This proposal exploits the opportunity for a comprehensive 13C NMR evaluation of fatty acid handling within the intact, functioning heart. The overall goal is to further develop and apply our kinetic 13C NMR methods to study the reciprocal relationship between the activity of the key regulator of fatty acid oxidation, carnitine palmitoyl transferase I (CPTI) and turnover of the myocardial triglyceride pool in normal and diabetic animal models. New and exciting findings from the previously funded period enable 13C NMR to distinguish between oxidative rates in the mitochondria and the rate of long chain fatty acid transport, via CPT1, as well as detect the incorporation rate of 13C-enriched palmitate into the myocardial triglyceride pool, all in the intact, beating heart. Therefore, this study explores the hypotheses that: 1) changes in the regulation of long chain fatty acid oxidation, via CPT1 activity, mediate the turnover rate of myocardial triglycerides and can be evaluated in whole hearts by a comprehensive examination of 13C enrichment kinetics; 2) Alterations in triglyceride content and turnover in the diabetic myocardium occur due to a combination of hyperlipidemia and changes in the expression of genes encoding enzymes for fatty acid uptake and oxidation pathways and that these can be distinguished via 13C NMR as independent mediators in the pathogenesis of diabetic cardiomyopathy. This hypothesis will be tested in both in both rat and mouse models of normal, diabetic, and genetically altered cardiac phenotypes. Specific aims are: 1) Determine reciprocal effects of fatty acid oxidation rates on triglyceride turnover via cardiac 13C NMR during partial inhibition of CPT1; 2) Examine long chain fatty acid oxidation rates, CPT1 activity, and triglyceride pool turnover in the hearts of rats with type-I (insulin deficient) diabetes and test for a potential link between triglyceride accumulation and turnover and the activation of protein kinase C; 3) Investigate effects of triglyceride pool size on the reciprocal nature of CPT1 activity and triglyceride turnover in a transgenic mouse model, overexpressing peroxisome proliferator-
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activated receptor alpha (PPAR-alpha), that mimics the diabetic phenotype for fatty acid and glucose metabolism and allows for dietary control of myocardial triglyceride pool size; 4) Examine long chain fatty acid oxidation rates, CPT1 activity, and triglyceride turnover in a more clinically relevant animal model of type II (insulin resistant) diabetes, the db/db mouse model, versus non-diabetic, wild-type mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANICAL REGULATION OF DILATED CARDIOMYOPATHY Principal Investigator & Institution: Omens, Jeffrey H.; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: Dilated cardiomyopathy is a disease of the heart that in most cases leads to decreased cardiac function and eventually to congestive heart failure. Mechanical factors such as stress and strain have been implicated as regulatory factors in diseases such as cardiac hypertrophy. The overall hypothesis of this proposal is that mechanical factors play a significant role in the tissue remodeling associated with dilated cardiomyopathy and cardiac failure. Sophisticated computational models in conjunction with experimental studies in rodents with different etiologies of heart failure (both genetic and surgically-induced) will help elucidate the role of mechanical factors in the progression of cardiac dilation and failure. The following hypotheses will be tested: (1) Dilated cardiomyopathy and eventual heart failure are mediated by mechanical loads on the heart, and the transition from a compensated hypertrophic state to cardiac failure is dependent on a critical level of stress or strain. Studies of cardiac function before and after this transitory phase can determine which mechanical factors are important. (2) A change in residual stress has important consequences for regional function in the heart, and may be a mechanism of dysfunction in heart failure. We will investigate this possibility by quantifying geometry and tissue structure in the stress-free state of the ventricle during the transition from dilation to failure, and use mathematical models to predict subsequent abnormal changes in diastolic and systolic wall stresses. (3) We expect that changes in. regional myocyte orientation, both at the cellular and global levels, are mechanisms of cardiac dilatation and failure. To test this hypothesis, local myocyte disarray and regional variations in laminar sheet orientation will be measured during the transition to failure. We will incorporate these measures into computational models of the heart, and then independently alter the myocyte orientation in the model, and compare the functional results with those obtained experimentally. We propose that these regional structural changes accompanies dilatory heart failure, and are mechanisms behind the reduction in fiber shortening and the ability of the wall to thicken during systole. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF ARRHYTHMIAS IN THE SETTING OF HEART FAILURE Principal Investigator & Institution: Pogwizd, Steven M.; Associate Professor; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 09-AUG-1991; Project End 31-JUL-2003 Summary: The goal of the proposed studies is to define the electrophysiologic and subcellular mechanisms underlying nonreentrant initation of ventricular tachycardia (VT) in the failing heart and its modulation by adrenergic stimulation. In the preceding grant interval, we have performed 3- dimensional mapping studies in arrhythmogenic
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Cardiomyopathy
experimental models of cardiomyopathy and in the failing human heart and demonstrated that VT initiates by a nonreentrant mechanism that is enhanced by catecholamines. The applicant has isolated myocytes from failing hearts and found alterations in Na/Ca exchange activity and intracellular calcium handling that could underlie the development of an arrhythmogenic transient inward current (Iti). Studies will be performed both in an arrhythmogenic rabbit model of nonischemic cardiomyopathy and in the failing human heart. The contribution of Alpha1-, Beta1and Beta2-adrenergic receptor stimulation to arrhythmogenesis in the failing heart will be determined by in vivo 3-dimensional mapping and in vitro electrophysiologic studies. Measurement of Alpha1-, Beta1-, and Beta2- adrenergic receptor density with microscopic resolution using autoradiographic techniques will determine whether the density of adrenergic subtype receptors parallel the arrhythmogenic effects of adrenergic subtype stimulation. To delineate how alterations in sarcoplasmic reticulum (SR) calcium flux, Na/Ca exchange activity and a calcium-activated chloride current lead to activation of a Iti in the failing heart, and to determine how the activation of Iti is enhanced by adrenergic stimulation, whole cell voltage clamping and measurement of intracellular calcium and SR calcium content will be performed in myocytes isolated from myopathic hearts. Lastly, to determine whether nonreentrant activation is due to triggered activity arising from delayed afterdepolarizations (as opposed to early afterdepolarizations or abnormal automaticity), studies will be performed in a novel isolated heart preparation in which transmural mapping in vitro will be combined with recording of monophasic and transmembrane action potentials. The results of these studies will provide new insights into the nature of nonreentrant activation in the failing heart and of the subcellular alterations that underlie adrenergic enhancement of arrhythmogenesis. The results will also provide the foundation for novel therapeutic approaches directed at nonreentrant activation that would be useful in the prevention of sudden death in patients with cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF DIABETIC CARDIOMYOPATHY Principal Investigator & Institution: Buttrick, Peter M.; Professor of Medicine and Physiology; Medicine; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: This project will investigate cellular events that lead to the development of left ventricular dysfunction in experimental animals and patients with diabetes mellitus. Diabetes mellitus is associated with a cardiomyopathy characterized in part by impaired diastolic relaxation. In previous animal studies, we have defined biochemical features of this myopathy that suggest that chronic protein kinase C activation and subsequent phosphorylation of the thin filament protein, troponin I, is central to the maladaptation and also that this process can be abrogated by treatment with an AT1 receptor antagonist. The present application will extend these observations. Two parallel lines of investigation are proposed: 1. Studies in diabetic rats and mice will be performed to establish the effects of transcriptional and post-translation modification of thin myofilament proteins on the relaxation properties and contraction kinetics of isolated fibers. These will include troponin I exchange experiments in skinned fibers to establish the functional of significance of TnI phosphorylation and also studies in transgenic mice expressing TnI protein with a mutated PKC site. 2. Studies will be performed on cardiocytes isolated from the myocardium of patients with diabetes in order to establish whether the same biochemical and mechanical abnormalities are
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present in human heart disease. It is hoped that this pronged approach will allow the extension of a fundamental experimental observation to clinical practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMBRANE-MEDIATED ALTERATIONS IN DIABETES Principal Investigator & Institution: Gross, Richard W.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-MAR-2007 Summary: A central theme in diabetic cardiovascular disease is the dysfunctional accumulation of lipids in critical cell-types (e.g., cardiac myocytes and macrophages) which underlie the intrinsic cardiomyopathy and accelerated atherosclerosis present in the diabetic patient. The unifying hypothesis of the program project grant is that lipid alterations in these cell types are due to fundamental changes in peroxisomal lipid flux mediated by alterations in intracellular phospholipases, PPAR mediated transcriptional regulation of critical regulatory proteins and altered lipid second messenger generation which collectively predispose candidate target cells to lipid accumulation and maladaptive pathophysiologic responses. In Project 1, we will examine the role of a novel peroxisomal calcium-independent phospholipase A2, iPLA2gamma, as a regulator of peroxisomal lipid synthesis and fatty acid beta oxidation in the cardiac myocyte. Additionally, Project 1 will examine the role of iPA2beta as a potential mediator of altered lipid metabolism and electrophysiologic dysfunction in diabetic myocardium. Dr. Kelly's Project, the role of PPARalpha as a primary determinant of the cardiac metabolic and functional phenotype present in the diabetic state will be examined utilizing mice over-expressing PPARalpha in cardiac myocyte specific fashion and a mice null for PPARalpha. Physiologic and biochemical alterations resulting from PPARalpha over-expression and the ventricular hemodynamic and metabolic abnormalities in diabetic myocardium will be compared. In Project 3, the role of altered peroxisomal lipid metabolism and intracellular phospholipase A2, activities in contributing to monocyte migration, lipid second messenger generation and lipid accumulation will be examined. The contribution of these factors in mediating the accelerated vascular response to mechanical to mechanical injury in diabetic rats will be examined. The contribution of these factors in mediating the accelerated vascular response to mechanical injury in diabetic rats will be examined. Dr. Muslig's Project the hypothesis that diabetic cardiomyopathy develops as a result of abnormal stimulation of Gq and Gi mediated signaling pathways leading to alterations in intracellular phospholipase activity, peroxisomal lipid metabolism and lipid second messenger generation will be studied. The contributions of cardiac myocyte phospholipases to Gprotein signaling will be examined. Collectively, these studies represent a synergistic, targeted, multi-disciplinary investigation aimed at elucidating the role of altered lipid metabolism and second messenger generation in critical cardiovascular cell types as the primary determinants of the excessive cardiovascular mortality and morbidity in diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MLC2V AND 2A IN CARDIAC DEVELOPMENT AND DISEASE Principal Investigator & Institution: Chen, Ju; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 05-SEP-2000; Project End 31-JUL-2004
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Summary: (the applicant's description verbatim): Utilizing a combination of genetic engineering in mouse model systems and miniaturized physiological technology, the proposed studies will test two principal hypotheses concerning MLC2v function: 1) MLC2a cannot functionally substitute for MLC2v in ventricular cardiac muscle; 2) Phosphorylation of MLC2v plays an important role in ventricular papillary muscle and cardiac function, and impairment of MLC2v phosphorylation will result in FHC. The overall goals of the proposal are to understand the functional differences between two cardiac MLC2 isoforms, MLC2v and MLC2a and the functional role of MLC2v phosphorylation. We hope to gain insight into mechanisms by which mutations in MLC2v cause cardiomyopathy and the roles of environment, physical state, and genetic background in the incomplete penetrance and variable phenotype of this disease. We will achieve these goals by creating several gene targeted mouse lines through knock-in, and site-specific mutagenesis followed by comprehensive histological, biochemical, and physiological analysis of the resulting cardiac phenotypes. Accordingly, the Specific Aims are: 1. To investigate the functional equivalence of MLC2a and MLC2v by examining the ability of MLC2a to rescue the C2v null mutant phenotype. This will be performed by knocking the MLC2a cDNA into the MLC2v endogenous locus thereby deleting MLC2v and leaving MILC2a under the control of the endogenous MLC2v promoter. 2. To understand the functional significance of MLC2v phosphorylation and to determine whether elimination of MLC2v phosphorylation is sufficient to induce a form of hypertrophic cardiomyopathy. Mouse lines will be generated in which the phosphorylation site(s) (Ser 15 or Ser 15 plus Ser 14) of the endogenous MLC2v gene have been mutated to Ala. 3. To understand the mechanism by which MLC2v mutations cause familial hypertrophic cardiomyopathy (FHC) with middle left ventricular chamber thickening. A mouse model will be created by introducing a Glu22Lys mutation into the ALC2v gene (A Glu22Lys mutation in human MLC2v causes familial hypertrophic cardiomyopathy). For each mouse model proposed in Specific Aims 1-3, comprehensive physiological assessment of cardiac function, and detailed biochemical and biophysical analyses of resulting cardiac muscle phenotypes will be performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR EPIDEMIOLOGY OF DILATED CARDIOMYOPATH Principal Investigator & Institution: Mestroni, Luisa; Director and Associate Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2005 Summary: This proposal addresses the molecular epidemiology of dilated cardiomyopathy by determining the frequency of disease gene mutations, and the genotype/phenotype correlations in the patient population, and their clinical relevance. Idiopathic dilated cardiomyopathy (DCM) is a disease affecting the cardiac muscle and is a primary cause of heart failure leading to heart transplant. The etiology of DCM is mainly unknown, but the disease is frequently inherited and genetically heterogeneous. Linkage studies have identified 17 FDC disease loci including a locus mapped by the P.I.'s laboratory on chromosome 9 in a large kindred with autosomal dominant FDC. Thus far, 8 disease genes have been identified: the P.I.'s laboratory has contributed to the discovery of mutations in dystrophin gene leading to X-linked FDC, and more recently, has discovered lamin A/C gene mutations in patients with FDC and variable skeletal muscle involvement. Other investigators have reported mutations in cardiac actin, deltasarcoglycan, desmin, tafazzin, beta-myosin heavy chain and troponin T leading to FDC. However, the prevalence, type and clinical relevance of cytoskeletal gene mutations in
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FDC, and in the overall DCM population are unknown. This application proposes a series of experiments designed to test the following hypotheses: 1) gene mutations are a frequent cause of FDC, 2) different gene mutations may have different frequency, different prognostic value, and different clinical relevance, 3) several FDC genes are still unidentified, and they are likely to encode cytoskeletal proteins. The Specific Aims of this proposal are: 1) to investigate of a cohort of patients with FDC and to evaluate their relatives to determine the inheritance pattern, the phenotype, the natural history, and recruit for molecular genetics studies; 2) to identify and characterize novel genes causing FDC using a candidate gene approach and a positional candidate cloning approach; 3) to analyze the molecular epidemiology of known and novel disease genes by studying the prevalence, type, and genotype/phenotype correlation of the FDC gene mutations in a large patient population with or without a familial trait. Clinical data, DNA and, in the case of FDC, lymphoblastoid cell lines have already been collected from 478 subjects, and we anticipate the enrollment of 20 to 30 new families/year. The experimental methods include mutation screening of known and novel candidate genes, positional cloning of the FDC gene on chromosome 9 by linkage and association studies, analysis of the frequency and genotype/phenotype correlations using a large database designed for these studies. The identification of the genes and mutations responsible for DCM will greatly increase the understanding of the molecular basis of this disease and will allow for the development of new molecular- based diagnostic and therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISM OF A MAMMALIAN CLASS I MYOSIN MOTOR Principal Investigator & Institution: Coluccio, Lynne M.; Boston Biomedical Research Institute 64 Grove St Watertown, Ma 02472 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2008 Summary: (provided by applicant): The association of some forms of cardiomyopathy, deafness, and blindness with defects in myosins, underscores the importance of studying these actin-associated, molecular motors. An understanding of the molecular mechanism of these enzymes can ultimately provide information crucial to the design of rational therapies to avert these diseases. Class I myosins are small, monomeric, mechanoenzymes with a motor domain, which binds actin and nucleotide; a regulatory region to which light chains attach; and a carboxy terminal tail. Class I myosins are widely expressed in mammalian cells and are predicted to mediate important actindependent processes such as cell migration and transport of cargo among intracellular compartments. The broad, long-term objective is to understand the enzymatic mechanism of the mammalian myosin-I, MYR 1, and how it relates to cell function. Key observations made in this laboratory have demonstrated the unique mechanochemical properties of MYR 1. MYR 1-actin exhibits a slow, biphasic transient interaction with nucleotide and a two-step powerstroke observed with single-molecule methods. These properties, not seen before for other myosins, presumably reflect the specialized adaptation of MYR 1 for particular cellular functions. The proposed experiments focus on detailing how MYR 1 interacts with actin and nucleotide. The specific aims are: (i) To investigate the contribution of two specific subdomains to MYR 1's unique mechanochemical properties using mutant proteins. The ability of mutant MYR 1 to interact with actin and nucleotide will be determined with steady and transient state kinetic analyses, in vitro motility assays and single molecule methods. (ii) To determine if MYR 1 undergoes nucleotide-dependent conformational changes using 3D
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reconstructions from cryo-electron micrographs of MYR 1-actin. These studies will allow for visualization of structural changes in MYR 1 during the myosin powerstroke. (iii) To determine if MYR 1 associates with specific subpopulations of actin filaments and whether specific structural elements in the motor domain modulate its binding to microfilaments. The ability of mutant MYR 1 to associate with actin filaments in complex with other actin-binding proteins will be determined in vitro with actin cosedimentation assays and in cells using expressed MYR 1. These studies will provide insight into how motors are targeted to particular sites in the cell, an important question in cell biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS IN T. CRUZI CARDIOMYOPATHY IN AIDS Principal Investigator & Institution: Tanowitz, Herbert B.; Professor; Pathology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): Chagas' disease is caused by the protozoan parasite T. cruzi and is now recognized as an emerging HIV/AIDS-related, opportunistic infection. Subsequent to immunosuppression there is reactivation of dormant organisms leading to myocarditis and necrotizing encephalitis. Since HIV-infected patients receiving HAART live for many years there is the likelihood that there will be repeated episodes of reactivation as their immune status waxes and wanes. Hence, progressive myocarditis and cardiovascular remodeling and chronic cardiomyopathy will likely develop in a more rapid fashion. In this application we have defined ventricular remodeling as changes in structure and function following myocardial damage together with characteristic molecular changes. These changes are the result of inflammation and/or necrosis. T. cruzi infection of the myocardium results in a dilated cardiomyopathy. Our overall objective is to examine some of the important signaling pathways involved in cardiac remodeling as a consequence of the T. cruzi infection. We plan to examine the consequences of T. cruzi-infection on cyclins in vitro, Our investigations clearly indicate that T. cruzi-induced ERK activation modulates the expression and/or activity of cyclins, which function as mediators of cellular proliferation and differentiation. Cyclins are responsible for remodeling in the cardiovascular system. Therefore, the kinetics of the expression of cyclins in infected cultured cells and co-culture systems. Since we have demonstrated that T. cruzi induces expression of cyclin D1, we will determine the molecular mechanisms involved in regulation of cyclin D 1 promoter activation in cardiac fibroblasts employing transient transfection/promoter assays. We plan to determine the consequence of T. cruzi infection on cyclins in mouse models of chagasic heart disease on. During acute T. cruzi infection there is activation of ERK, transcription factors AP-1 and NF-kB and increased expression of cyclin D 1 in the myocardium. Therefore, in the mouse model of Chagas' disease the kinetics of expression of cell cycle regulatory proteins in the cells of the myocardium of T. cruzi-infected mice will be determined and correlated with progression of cardiomyopathy. The mechanisms underlying the alterations in these proteins in the myocardium will be investigated by a variety of techniques including immune complex assays and cell proliferation experiments. The contribution of cyclin D 1 in cardiovascular remodeling will be investigated utilizing mouse models including cyclin D1 null mice and mice in which NF-r.d3 and ET-1 have been selectively deleted from cardiac myocytes. These studies will lead to a better understanding of cardiac
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remodeling in chagasic cardiomyopathy, an emerging opportunistic infection in AIDS. In addition, it will provide potential targets of adjunctive therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR MECHANISMS OF MATRIX GLA PROTEIN Principal Investigator & Institution: Bostrom, Kristina I.; Assistant Professor of Medicine; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Calcification of vessels and cardiac valves causes a multitude of clinical problems including congestive heart failure, cardiomyopathy, angina, and complications during interventional and surgical procedures. Currently, there are no medical therapies able to prevent or reverse calcification. An understanding of the underlying mechanisms would identify new targets for developments of such therapies. Mice deficient in Matrix GLA Protein (MGP) develop extensive vascular calcification with replacement of the vascular wall by typical cartilage cells. This suggests that MGP plays a role in vascular cell differentiation. We hypothesize that the function of MGP is to act as an inhibitor of bone morphogenetic protein 2 (BMP-2), a potent inducer of calcified tissues. In absence of MGP, vascular cells may be induced by BMP-2, and differentiate into cartilage and bone cells instead of vascular smooth muscle cells. We hypothesize that this effect of MGP occurs early in vessel formation. The proposal has four aims. The first is to study the effect of increased levels of MGP on cell differentiation induced by BMP-2 in tissue culture, and then use this system to identify key sequences in MGP by altering the MGP protein. The second aim is to characterize the putative binding between MGP and BMP-2 by using cross-linking and binding studies. The third aim is to identify when in the development of MGP deficient mice, vascular cells lose their normal characteristics and differentiate into cartilage cells, using specific markers for smooth muscle and cartilage cells. Finally, we will generate transgenic mice deficient in normal MGP but expressing selected key sequences of MGP identified in previous aims to affect cell differentiation, and to study the effect of these sequences on in vascular calcification in vivo. Understanding the molecular mechanisms of MGP will provide information that is widely applicable to the development of vascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR PATHOGENESIS OF CARDIAC DYSFUNCTION Principal Investigator & Institution: Giroir, Brett P.; Associate Professor; Pediatrics; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: The goal of this proposal is to determine the molecular mechanisms of cardiac dysfunction that occurs during septic shock and following thermal trauma. Previous work has demonstrated that cardiac dysfunction is mediated by the cytokine tumor necrosis factor-alpha (TNF), which is produced locally in the myocardium by cardiac myocytes. This proposal utilizes novel molecular and genetic strategies to investigate the mechanisms of TNF's detrimental effects and to develop therapeutic approaches for TNF-related cardiac contributions. First, we will study transgenic mice in which TNF is constitutively expressed only by cardiac myocytes. These mice develop profound cardiac dysfunction, cardiomyopathy, myocarditis, and cardiac failure which mimics cardiac contractile dysfunction in humans. By breeding these transgenic animals
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to mice which have undergone targeted disruption of iNOS (inducible nitric oxide synthase), IRAK (IL-1 receptor associated kinase), and ICAM-1 / P-selectin, as well as by pharmacological inhibition of specific pathways, we will quantitatively determine the involvement of iNOS, IL-1, and transmigrated leukocytes in the pathogenesis of myocardial failure. Cardiac phenotype will be characterized primarily by in vitro Langendorff perfusion of isolated mouse hearts; confirmatory longitudinal analysis of function will be accomplished in vivo by ECG-gated MRI imaging. Physiologic findings will be correlated with survival, post-mortem histology, and the pattern of cardiac gene expression. Next, we will optimize the transgenic animal model by developing a binary transgene system which is cardiac specific, and regulatable by dietary tetracycline. Through this system, we will determine if the effects of TNF are related to dose and duration of expression. We will describe the cascade of secondary cytokines induced by TNF. We will also determine whether low-level, transient expression of TNF may be evolutionary adaptive, and serve a protective role against subsequent cardiac insults. By understanding the molecular mechanisms by which TNF impedes myocardial performance, it will be possible to develop specific, targeted therapeutic strategies for the treatment of sepsis, burn trauma, and other TNF-related cardiac conditions such as cardiomyopathy, myocarditis, and ischemic heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Cooper, Thomas; Associate Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 08-FEB-1999; Project End 31-JAN-2004 Summary: The goal of this project is to determine the molecular basis for myotonic dystrophy (DM), a dominantly inherited disease caused by an expanded CTG trinucleotide repeat in the 3' untranslated region of the DMPK. DM is a multi-systemic disorder characterized by progressive skeletal muscle weakness, cardiomyopathy and arrhythmias, cataracts, and abnormalities in brain and endocrine function. Despite identification of the genetic defect six years ago, the molecular basis of the disease is unknown. DMPK transcripts containing the expanded repeat accumulate in nuclear foci. One hypothesis is that the expanded repeat creates a grain-of-function in the DMPK RNA which has a trans-dominant effect on the expression of other genes. A proposed mediator of the nucleus of DM cells. Our preliminary results establish the previously hypothesized link between the nuclear accumulation of expanded-CUG transcripts, nuclear accumulation of CUG-BP, and alteration of tissue-specific RNA processing in DM cells. We demonstrate that CUG-BP positively regulates splicing of the cardiac troponin T (cTNT) alternative exon 5 by binding to a previously characterize musclespecific splicing element. cTNT exon 5 is aberrantly included in DM striated muscle, consistent with nuclear accumulation of a positive splicing regulator. The transdominant effect on cTNT splicing was reproduced in normal muscle cells by cotransfection of cTNT minigenes with expanded DMPK minigenes containing up to 1440 CTG repeats. Wild-type cTNT minigenes but not minigenes with a mutated CUG-BP binding site expressed enhanced levels of exon 5 inclusion demonstrating the role of CUG-BP in the trans-dominant effect. The goals of this proposal are to: (i) characterize expression of a novel protein closely related to CUG-BP (etr-3) recently identified in an EST library (ii) determine the mechanism of etr-3 and CUG-BP nuclear accumulation in DM cells; (iii) identify genes that are regulated post-transcriptionally by etr-3 and CUGBP which are likely to directly mediate DM pathogenesis; (iv) establish stable fibroblast and muscle cell lines that inducible express expanded-CUG RNA; (v) establish lines of
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transgenic mice that express expanded-CUG RNA. This proposal will directly test the hypothesis that the expanded trinucleotide creates a gain-of-function mutation in the RNA. It will also establish experimental systems to investigate the basis of a novel pathogenic mechanism and ultimately, test means of therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR PHYSIOLOGY OF MYOCARDIAL TROPONIN I VARIANTS Principal Investigator & Institution: Murphy, Anne M.; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 13-SEP-1999; Project End 31-MAR-2004 Summary: (the applicant's description verbatim): Contraction of the heart occurs through regulated interactions of the myofilament proteins in response to increasing intercellular calcium concentrations. Contractile dysfunction associated with myocardial disease is linked to an altered response of contractile proteins to calcium. The inhibitory subunit of troponin, troponin I, is a key regulatory protein which modulates contractility based on its phosphorylation status. Recently, modifications and mutants of troponin I have been associated with ischemic injury, heart failure and cardiomyopathy. The goal of this proposal is to understand how disease related alterations to troponin I modify its function and play a central role in myocardial disease states. A comprehensive approach is proposed to delineate the both the pathophysiology and molecular mechanisms of alteration of function produced by troponin I variants in the heart. Specific variants which will be characterized are a) truncated variant (I - 193), a loss of 16 amino acid residues from the carboxy-terminus, which recapitulates the truncated form produced by calcium dependent proteolysis in stunned myocardium, and b) troponin I variants with site-directed mutations in protein kinase A and protein kinase C phosphorylation sites to determine the role of these sites in intrinsic contractility, preconditioning, ischemia/reperfusion and heart failure and finally c) a troponin I variant with a single amino acid mutation in the inhibitory region reproducing a recently described mutant found in a familial hypertrophic cardiomyopathy. Methods include measurements of ventricular mechanics in transgenic mice using a miniaturized conductance-micromanometer catheter, studies of steady state force-calcium relationships in fura-2 loaded intact trabeculae from these mice and in vitro experiments with recombinant protein and synthesized peptides to dissect the altered biochemical properties of these troponin I variants. This work will determine a molecular mechanism of myocardial stunning, the role of troponin I phosphorylation in vivo and the pathophysiology of one form of hypertrophic cardiomyopathy. It is also anticipated that the information gained will ultimately provide a rational basis for the development of novel therapies for cardiac dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MYOCARDIAL PPAR ALPHA IN DIABETIC CARDIOMYOPATHY Principal Investigator & Institution: Kelly, Daniel P.; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Cardiac dysfunction is a common and important manifestation of diabetes mellitus. It is well recognized that cardiomyopathy occurs frequently in diabetic patients in the absence of known cardiac risk factors. Although little is known about the pathogenesis of diabetic cardiomyopathy, evidence is emerging that cardiac dysfunction
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in the diabetic heart is related to perturbations in myocardial metabolism caused primarily or secondarily by insulin deficiency or resistance. In uncontrolled diabetes, the myocardial extraction and utilization of fat is markedly increased such that the diabetic heart relies almost exclusively on mitochondrial fatty acid oxidation (FAO) for its ATP requirements. Recent studies have defined an important role for the lipid-activated transcription factor, the peroxisome proliferator-activated receptor alpha (PPARalpha), in the control of cardiac fatty acid utilization pathways. Our preliminary data indicates that the activation of cardiac fatty acid utilization in the diabetic heart is mediated by the PPARalpha gene regulatory pathway. Our preliminary data indicates that the activation of cardiac fatty acid utilization in the diabetic heart is mediated by the PPARalpha gene regulatory pathway. This proposal is designed to test the hypothesis that lipid metabolic alterations secondary to increased activity of PPARalpha lead to pathologic remodeling in the diabetic heart. Such pathologic remodeling could occur due top increased oxygen consumption or through toxic lipid intermediates generated by peroxisomal or mitochondrial pathways. This hypothesis will be tested by the phenotypic characterization of mice with cardiac-specific over- expression of PPARalpha (MHCPPAR mice). First, the lipid metabolic and cardiac functional phenotypic of multiple independent lines of MHC-PPARalpha transgenic mice will be evaluated and compared with that of mice rendered diabetic via administration of streptozotocin. Second, the role of PPARalpha in the expression and severity of diabetic cardiomyopathy will be determined by altering its activity via genetically engineered loss-of-function (PPARalpha null mice) and gain- of-function (MHC-PPAR mice) in the context of three different murine models of diabetes. Lastly, the role of altered peroxisomal function in MHC-PPAR mice compared to diabetic mice. The long term goal of this project is to delineate the precise molecular and metabolic bases for diabetic cardiomyopathy including identification of specific lipid mediators of cardiac dysfunction. This work should lead to the development of novel therapeutic strategies aimed at modulating cardiac lipid metabolism to reduced the cardiovascular morbidity and morality in diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOCARDIAL PROTEIN SYNTHESIS AFTER THERMAL INJURY Principal Investigator & Institution: Lang, Charles H.; Professor and Vice-Chairman; Cellular/Molecular Physiology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2002; Project Start 10-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): Myocardial dysfunction remains a major cause of morbidity and mortality in patients after thermal injury. Our preliminary data provide evidence that the burn-induced decrease in intrinsic mechanical function is associated with an impairment in myocardial protein synthesis and translational efficiency. The working hypothesis to be tested is that the burn-induced decrease in myocardial protein synthesis is mediated by defects in translational efficiency resulting from an impairment in both peptide-chain initiation and elongation, and that these changes are mediated by the overproduction of tumor necrosis factor (TNF)a which alters the responsiveness of the heart to insulin-like growth (IGF)-l and growth hormone (GH), To address the questions implicit in this hypothesis, the proposed research has the following specific aims: (1) to determine the temporal progression of burn-induced changes in protein synthesis, indices of peptide-chain initiation and myocardial function, and to determine whether these changes are mediated by TNFa; (2) to determine the mechanism by which thermal injury decreases activity of eIF2B in heart, by assessing the phosphorylation of
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elF2Be, content of p67, and the importance of alterations in kinase and phosphatase activities directed towards eIF2a and eIF2Be; (3) to determine the mechanism by which burn alters elF4E availability, by assessing the phosphorylation status of the various 4Ebinding proteins and p7OS6 kinase, and quantitating the degradation of eIF4G; (4) to determine the mechanism by which burn impairs peptide-chain elongation in heart, by quantitating the rate of elongation under in vivo conditions and by determining the myocardial content and phosphorylation state of elongation factors EFI and EF2; and (5) to determine the signaling mechanisms by which burn injury impairs GH and IGF-I action in heart. Our data suggest that the bum-induced changes in cardiac protein synthesis and translation initiation are relatively unique, and do not occur in skeletal muscle in response to burn or in heart in response to other traumatic conditions. Overall, the research will elucidate the mechanisms by which myocardial protein synthesis is reduced after thermal injury, leading to the better understanding and treatment of the resulting cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOCYTE CELL DEATH IN THE INFARCTED HEART Principal Investigator & Institution: Anversa, Piero; Professor and Director; Medicine; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: The objective of this proposal is to demonstrate that postinfarction cardiomyopathy is dependent upon the changes in size, shape, and number of the surviving myocytes, whereas the alterations in the infarcted myocardium play a minimal role in the long-term evolution of ventricular remodeling and chamber dilation. work during this funding period has documented that the cellular events which characterize the reactive hypertrophy of the spared myocardium, acutely and at the completion of healing, fail to normalize ventricular pump function, leading to a persistent elevation in diastolic wall stress. This mechanical stimulus is postulated by be responsible for continuous myocyte lengthening and the in series addition of newly formed cells through the mechanism of myocyte cellular hyperplasia. Extreme degrees of ventricular dilation may be generated by these cellular growth processes and intractable ventricular dysfunction and failure may supervene. Such an unfavorable outcome lies in the inability of myocytes to increase in diameter and/or be added in parallel within the wall to expand mural thickness and counteract the elevation in diastolic wall stress dictated by the larger cavitary volume. In a similar fashion, hypertensive hypertrophy, with its attendant changes in myocyte diameter and cross section area, may have exhausted one of the most important compensatory reactions of myocytes, which would tend to attenuate the consequences of ventricular dilation after infarction. Thus, the detrimental impact of hypertension induced concentric hypertrophy, prior to coronary artery occlusion, may reflect this phenomenon. Therefore, the recognition of control mechanisms implicated in the transmission of mechanical signals to myocytes and the initiation of the molecular events leading to increases in myocyte diameter, myocyte length and myocyte number may have important clinical implications in the prevention and treatment of the cardiomyopathy generated by myocardial infarction alone or in combination with hypertension. Accordingly, the hypotheses have been made that activation of alpha1b adrenergic receptors and AII receptors, and transmission of signals by these receptors induce myocyte hypertrophy and selectively mediate the increases in myocyte cell length and diameter, respectively. On the other hand, cellular hyperplasia is believed to be triggered by the expression of growth factor receptors on myocytes. In summary,
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myocyte hypertrophy and hyperplasia are assumed to both contribute to accommodate the sudden increase in work load associated with myocardial infarction. When the acute phase has subsided, myocyte hypertrophy, characterized by lengthening of the cells, becomes the predominant factor responsible for ventricular dilation. However, longterm restructuring of the ventricle after infarction may occur exclusively by the addition in a series of newly formed myocytes which may lead to extreme degrees of ventricular dilation. Hypertension may accelerate this sequence of events worsening the myocardial response to infarction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOCYTE FUNCTION IN CARDIOMYOPATHIC CREB A133 MICE Principal Investigator & Institution: Moss, Richard L.; Robert Turell Professor and Chair of Phy; Physiology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2003 Summary: Dilated cardiomyopathy (DC) represents an important cause of cardiovascular morbidity and mortality and consumes a disproportionate share of medical resources in this country. Despite recent advances in the treatment of DC, this disorder has a poor prognosis with 5 year mortality rates of 20-50 percent. Progress in understanding the pathophysiology of DC and in devising new therapies for this disorder has been limited by our relative lack of understanding of the molecular pathophysiology of the disease and by the lack of a small animal model which closely resembles the anatomical, physiological, and clinical features of the human disease. The investigators have recently shown that transgenic mice expressing a dominant-negative form of the CREB transcription factor (CREBA133) under the control of the cardiacspecific alpha-MHC promoter reproducibly develop DC that resembles many of the anatomical, physiological and clinical features of human DC. In the studies described in these 3 collaborative R0I applications, the investigators propose to use this new mouse model to better understand the molecular pathways by which CREB regulates cardiac myocyte homeostasis and how perturbations in these pathways produce DC. Specifically, they will 1) elucidate the CREB-dependent signaling pathways that are required to maintain cardiac myocyte homeostasis and determine how these pathways are perturbed in the CREBA133 mice with DC, 2) determine the role of apoptosis in the CREBA133 DC and test the hypothesis that the cardiomyopathic phenotype can be ameliorated by expression of anti-apoptotic genes in the heart, 3) study excitationcontraction coupling, contractility, and calcium homeostasis in the CREBA133 cardiac myocytes, 4) understand the myofibrillar and SR defects underlying cardiac myocyte dysfunction in the CREBA133 mice, 5) study ventricular remodeling and LV-arterial coupling during the development of DC in the CREBA133 mice, and 6) determine the effects of exercise conditioning, gender, and different modes of inhibiting the renin angiotensin system on progression of DC in the CREBA133 mice. These studies represent the continuation of an established collaboration between molecular biologists (Leiden), cell physiologists (Moss) mouse and human physiologists (Lang, Spencer) and clinical cardiologists (Leiden, Lang, Spencer) from the Universities of Chicago and Wisconsin. Taken together the results of this work should provide us with important new insights into the molecular mechanisms underlying human DC and CHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC OXIDE METABOLIC CONTROL IN PREGNANCY Principal Investigator & Institution: Hintze, Thomas H.; Professor; Physiology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2003; Project Start 15-DEC-1993; Project End 31-DEC-2006 Summary: (provided by applicant): The cardiovascular adjustments that occur during pregnancy include chronic increases in cardiac output, falls in total peripheral vascular resistance and tachycardia. There is an upregulation of endothelial nitric oxide synthase in almost all vascular beds studied in the gravid female including skeletal muscle, kidney and utems or placenta. The upregulation of eNOS directly contributes to the fall in TPR which is not confined to the placenta. Many studies have investigated the role of NO in the control of vascular resistance or how NO may buffer vasoconstriction and that a defect in NO production may be involved in pre-eclampsia. Despite increasing evidence that NO also modulates mitochondrial metabolism and substrate uptake by the heart, i.e. prevents glucose uptake and facilitates fatty acid uptake, there are literally no studies that have investigated the role of increased eNOS in the control of substrate uptake and organ oxygen consumption at all. We have previously shown that NO by interacting with cytochrome oxidase in heart, kidney and skeletal muscle serves to maximize the ratio of oxygen consumed to external work performed ie. increases efficiency. We have also shown that when eNOS produces NO in the heart and elsewhere, glucose uptake is prevented. It is important to re-emphasize that pregnancy is characterized by increased eNOS gene expression and increased NO production in every vascular bed of the mother. Furthermore, glucose uptake by the mother is low even insulin insensitive and this is thought to increase the amount of glucose available for uptake through the placenta to support fetal metabolism, since the placenta does not take up fatty acids. In addition a small but significant number of mothers go on to have a post-partum cardiomyopathy often leading to heart transplantation, perhaps when adjustments that occur during pregnancy do not regress after parturition. Thus the focus of this competitive renewal application will be the role of NO in the control of oxygen and substrate use during pregnancy with particular reference to the heart and coronary circulation. In the first specific aim, we will examine the role of NO in the control or metabolism in aged eNOS KO mice. The second aim will focus on the role of NO in the pregnant eNOS KO mouse whereas the third specific aim will focus on the role of NO in cardiac glucose and oxygen uptake in the rat heart during pregnancy. Finally aim 4 will use chronically instrumented conscious pregnant dogs to address the role of NO in the control of cardiac function, substrate use and oxygen consumption during pregnancy and after parturition. For the first time we wilt perform a systematic mechanistic investigation into the role of NO in the control of cardiac oxygen and substrate use during pregnancy. These studies have direct application to the physiology of pregnancy and to the potential mechanisms resulting in post partum cardiac dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NO AND OXIDATIVE STRESS IN HUMAN MYOCARDIAL FAILURE Principal Investigator & Institution: Givertz, Michael M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: The overall goal of this project is to determine the functional significance of myocardial nitric oxide (NO) and oxidative stress in humans with heart failure (CHF). Recent evidence suggests that NO is increased in failing human myocardium and may contribute to the pathophysiology of CHF. In addition, increased myocardial oxidative
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stress has been demonstrated in heart failure. In vitro studies indicate that reactive oxygen species (ROS) can exert direct toxic effects on the myocardium associated with impaired contractility, fetal gene expression and cell death. Moreover, antioxidants have been shown to attenuate the negative inotropic effects of ROS and prevent the development of heart failure in animal models. In left ventricular (LV) failure, the heart rate- mediated increase in contractility (force-frequency relationship) is attenuated, flat or even inverted. While the failure to increase contractility with tachycardia likely contributes to the reduced cardiac output response and exercise intolerance observed in patients with CHF, the underlying mechanisms are poorly understood. In Specific Aim 1, we will test the hypothesis that increased myocardial NO synthase (NOS) activity attenuates the force- frequency relationship in humans with LV failure by measuring the changes in the peak rate of rise of LV pressure (+dP/dt) that occur with increasing heart rates before and during intracoronary infusion of NG-monomethyl-L-arginine, an inhibitor of NOS. In Specific Aim 2, we will test the hypothesis that increased myocardial oxidative stress attenuates the force-frequency relationship in humans with LV failure by determining the force- frequency relationship before and during intracoronary infusion of the antioxidant ascorbic acid. Aims 1 and 2 are invasive protocols that will assess the acute functional significance of myocardial NO and oxidative stress in heart failure. In Specific Aim 3, we will test the ability of a novel, noninvasive system to detect acute changes in contractile state by measuring LV endsystolic elastance during atrial pacing tachycardia and intracoronary dobutamine infusion in patients with dilated cardiomyopathy. If we show that this new technology is able to measure changes in contractility in the catheterization laboratory, we will assess its ability to detect chronic changes in LV performance by measuring end-systolic elastance before and after therapy with antioxidants and/or anti- inflammatory agents in patients with systolic heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NRTI-INDUCED MITOCHONDRIAL CARDIOMYOPATHY Principal Investigator & Institution: Wallace, Kendall B.; Professor; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Cardiovascular disease is a growing complication of HIV. Although there is an increased incidence associated with the infection itself, it is further complicated by the antiviral therapy prescribed to treat the disease. The cornerstone of the HAART drug regimen for treating HIV are nucleoside analog reverse transcriptase inhibitors (NRTIs), which inhibit viral RNA-dependent DNA polymerases. However, these drugs are also recognized by host cell DNA polymerases including Polg, which is responsible for replicating the mitochondrial genome. As a result, the NRTIs inhibit mtDNA replication and biogenesis leading to mitochondrial depletion, which is manifested as a dose-limiting lactic acidosis and life-threatening cardiomyopathy. Although there is considerable evidence implicating mitochondrial depletion in the pathogenesis of NRTI toxicity, little is known regarding the bioenergetic characteristics responsible for the mitochondrial phenotype. The purpose of this investigation is identify which NRTIs induce mitochondrial cardiomyopathy in animal models at relevant doses and to fully characterize the mitochondrial bioenergetic deficits that underlie the metabolic disorder. We propose that the loss of coordinated expression of the nuclear and mitochondrial genomes leads to the assembly of poorly coupled electron transport chains, resulting in a loss of efficiency of oxidative phosphorylation
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accompanied by the catalytic liberation of highly reactive oxygen free radicals. Mitochondrial cardiomyopathy likely reflects both bioenergetic failure and increased oxidative damage owing to this interference with mitochondrial biogenesis. The results of this investigation will provide valuable insight into distinguishing which NRTIs are cardiotoxic and identifying the underlying mechanisms in the pathogenesis of cardiac injury. This information will be essential to predicting possible interactions between components of the HAART drug regimen and for developing reliable biomarkers and/or new treatment strategies designed to minimize the cardiomyopathy and thus improve the clinical success of HIV pharmacotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE RESTRICTION
STESS
AND
HEART
FAILURE
BY
COPPER
Principal Investigator & Institution: Kang, Y James.; Professor; Medicine; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2005 Summary: Dietary copper restriction causes cardiac hypertrophy, ultimately leading to heart failure. A proposed mechanism for this cardiomyopathy is the accumulation of reactive oxygen species. Using a cardiac-specific metallothionein (MT)- overexpressing transgenic mouse model, we have observed that elevation of this potent antioxidant in the heart suppresses the progression of heart hypertrophy and likely results in the retarded development of heart failure induced by dietary copper restriction. This observation suggests that oxidative stress may play a crucial role in the pathogenesis of heart failure. We therefore propose to test the hypothesis that oxidative stress triggers the transition from heart hypertrophy to failure induced by copper deficiency. We will use the cardiac-specific MT- overexpressing transgenic mouse model to carry out the following specific aims: (1) To define the role of oxidative stress in the transition from heart hypertrophy to failure, a detailed time- course study of the development of heart failure by dietary copper restriction will be performed. In particular, this study will focus on defining the cause-and-effect relationship between oxidative stress and dynamic changes in cardiomyopathy, cardiac dysfunction and heart failure. (2) To determine cellular events involved in the transition from heart hypertrophy to failure, the significance of cell death in the pathogenesis will be defined by immuno-gold TUNEL and electron microscopy in combination with a novel procedure using cardiac alpha-sarcomeric actin antibody to label necrotic cells. The relative contributions of apoptosis and necrosis to the total cell loss will be analyzed. (3) To investigate signaling pathways leading to myocardial cell death during the transition from heart hypertrophy to failure, oxidative stress-induced mitochondrial cytochrome c release and activation of caspase-9 and -3 will be examined by immunohistochemical method, enzymatic assay and Western blot analysis. The consequence of caspase inhibition will be analyzed in order to dissect major pathways leading to cell death. (4) To examine the role of atrial natriuretic peptide (ANP) and tumor necrosis factor-alpha (TNF-alpha) in the late phase transition from heart hypertrophy to failure, dynamic changes in ANP and TNF-alpha production will be studied. Molecular mechanisms of up-regulation of these cytokines will be analyzed through examining the activation of transcription factors NF-kappaB and AP-1. (5) To explore possible mechanisms by which MT inhibits oxidative stressmediated myocardial cell death induced by dietary copper deficiency, the effect of MT on oxidative stress- mediated mitochondrial membrane changes that lead to cytochrome c release will be examined. The overall goal of this study is to define the role of oxidative stress in copper deficiency-induced pathogenesis of heart failure. This study will give
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critical insights into the signaling pathways and molecular mechanisms of failure induced by copper deficiency. Importantly, the data obtained will provide valuable information for novel experimental as well as clinical approaches for possible interventions of the transition from heart hypertrophy to heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS OF CHAGAS HEART DISEASE Principal Investigator & Institution: Engman, David M.; Associate Professor; Pathology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by the applicant): The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas' disease, an illness that causes severe morbidity and death among millions of Latin Americans. The most common, and most serious, adverse effect of chronic infection with this parasite is Chagas heart disease (CHD), a dilated cardiomyopathy of uncertain etiology. A number of mechanisms have been proposed for the pathogenesis of CHD, two of which are the subject of considerable controversy. Because parasites are scarce in or absent from the heart tissues of Chagas' patients who succumb to heart failure, autoimmunity has been proposed to be responsible for disease pathogenesis. More sensitive techniques, such as in situ PCR and immunohistochemistry, have been used to analyze these hearts and, indeed, parasite DNA and antigen are present. These findings support the hypothesis that parasiteinduced damage plus host immunity to parasite antiqens is the inflammatory stimulus. Another confounding factor is that different combinations of parasite and animal strains give different outcomes, which, in actuality, is reflective of the human disease. To test the autoimmunity hypothesis for CHD pathogenesis, while simultaneously considering the parasite immunity hypothesis, we developed a mouse model of CHD (T. cruzi Brazil strain infection of male A/J mice) in which strong cardiac autoimmunity and parasitespecific immunity rapidly develop upon infection. Our research during the past several years indicates that (i) cardiac autoimmunity develops upon infection that is of similar magnitude and quality as that induced by immunization with cardiac proteins in adjuvant (purely autoimmune), (ii) autoimmunity involving a number of cardiac antigens develops in infected animals, (iii) autoimmunity to cardiac myosin may develop via the mechanisms of molecular mimicry and bystander activation, and (iv) selective suppression of myosin autoimmunity does not eliminate tissue inflammation in infected animals, suggesting that other autoimmune responses may be significant and/or that parasite-specific immunity hypothesis is sufficient to give tissue inflammation. The Specific Aims of our research are (i) to investigate the molecular mimicry mechanism of myosin autoimmunity in CHD, (ii) to identify additional cardiac auto-antigens and determine their roles in CHD pathogenesis and (iii) to test the autoimmune and parasite immune hypotheses for CHD pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AMYLOIDOSIS
PATHOGENESIS
OF
HEREDITARY
TRANSTHYRETIN
Principal Investigator & Institution: Benson, Merrill D.; Professor; Medical and Molecular Genetics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-MAR-2004
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Summary: (from abstract): The overall objective of this proposal is to define the pathophysiology of the autosomal dominant transthyretin amyloidoses. These diseases, while considered rare, are actually being recognized in increased numbers of kindreds throughout the world and especially in the United States. Transthyretin amyloidosis is usually associated with peripheral neuropathy, nephropathy, and cardiomyopathy which present as late-onset (adult) disease with high degrees of morbidity and mortality. To date at least 72 variants of transthyretin (TTR) have been found to be associated with systemic amyloidosis which is inherited as an autosomal dominant disease. Of particular concern is the fact that: 1) it has recently been shown that there are elderly individuals who develop transthyretin amyloid cardiomyopathy (senile cardiac amyloldosis) in the absence of any detectible mutation in transthyretin; and, 2) there is a high prevalence of one particular transthyretin mutation (isoleucine 122) in the American Black population and this is manifest as amyloid cardiomyopathy. These two findings suggest that, as the population ages, amyloid heart disease will become of greater significance to the American population. Previous studies have centered on determining structural changes of transthyretin which are related to amyloid formation. Structures of amyloid forming variants methionine 30, serine 84, alanine 60, arginine 10, tyrosine 77 have been compared to structures of non amyloid forming threonine 109, serine 6, methionine 119 and normal transthyretin. No common structural change has been found to explain initiation of the fibril forming process but preliminary data suggest that solvent accessability to variant transthyretin dimers may allow a proteolysis event which could lead to the initiation of fibril formation. Metabolic studies using radiolabelled variant and normal transthyretins have suggested increased plasma clearance of variant proteins. The Specific Aims will test the hypothesis that single amino acid substitutions in transthyretin result in changes in tertiary structure of the transthyretin molecule which allow alterations in metabolism of the variant molecule and its associated normal monomers to lead to amyloid formation. Transthyretin proteins isolated from tissues of patients with amyloidosis will be studied to characterize proteolytic peptides and determine if partial proteolysis with generation of carboxyl terminal peptides is a factor in amyloid fibril formation. Fibril forming potential of these fragments will be tested by producing recombinant protein of residues 49 - 127 and testing fibril formation with and without full-length transthyretin in vitro. A new Specific Aim will test the hypothesis that the ratio of the various tetrameric forms of transthyretin affects the propensity to form amyloid fibrils. To accomplish this aim a dual expression system in baculovirus coexpressing normal TTR and variant TIR has been developed. These studies are directed at developing methods to prevent amyloid formation from variant TTR proteins and, thereby providing therapeutic options for a disease which at the present time has no specific therapy other than liver transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POST DPP FOLLOW-UP STUDY Principal Investigator & Institution: Goldberg, Ronald B.; Chief, Division of Diabetes and Metaboli; Medicine; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 20-AUG-1994; Project End 31-JAN-2008 Summary: (provided by applicant): The Diabetes Prevention Program is a multicenter controlled clinical trial examining the efficacy of an intensive life-style intervention or metformin to prevent or delay the development of diabetes in a population selected to be at high risk due to the presence of impaired glucose tolerance (IGT). Development of diabetes, defined by 1997 ADA criteria, is the primary outcome while cardiovascular
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disease and its risk factors are important secondary outcomes. The DPP began recruitment in mid-1996. At the time of this application, total study exposure is a mean of approximately 3 years (range 2 to 5) with a total of approximately 10,000 patient years in the 3,234 volunteers in the 3-arm study. On the basis of a statistically significant and clinically compelling decrease in the development of diabetes in the life-style intervention and metformin-treated groups (58% and 31% reductions, respectively) compared with the placebo treated group, the DPP Data Monitoring Board and NIDDK ended the masked treatment phase of the study in May, 2001, one year earlier than originally planned. This application is designed to take further advantage of the scientifically and clinically valuable cohort of DPP volunteers and the large volume of data collected during the study. The highly compliant DPP cohort, including 45% minorities, is the largest IGT population ever studied. Moreover, the subcohort that has developed diabetes (n approximately 700) has been followed from near the exact time of diabetes onset. Clinically important research questions remain in the wake of the DPP. The carefully collected, centrally measured and graded data in this cohort should help to answer, definitively, a number of important questions regarding the clinical course of IGT and early onset type 2 diabetes. Specific aims include: 1. Examine the long-term effects and durability of prior DPP intervention on the major DPP outcomes including diabetes, clinical cardiovascular disease, atherosclerosis, CVD risk factors, quality of life and cost-benefit; 2. Determine the clinical course of new onset type 2 diabetes and IGT, in particular regarding microvascular and neurologic complications; 3. Determine the incidence of cardiovascular disease (CVD), CVD risk factors and atherosclerosis in new onset type 2 diabetes and IGT; and 4. Examine topics 1-3 in minority populations, men vs. women, and in older subjects in the DPP. The current application is for 5 years of funding, although the some of the goals of the projects described will require a 10-year study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREDICTION OF CARDIOMYOPATHY IN TYPE I DIABETES BY MRS Principal Investigator & Institution: Pohost, Gerald M.; Director; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Description (provided by applicant): Congestive heart failure is a leading cause of morbidity and mortality in the United States and diabetes has been recognized as a major risk factor for the development of this disease. However, there is a lack of consensus regarding the existence of a diabetes-specific cardiomyopathy as well as the importance of vascular and non-vascular alterations in the development of diabetesrelated cardiac disease. We recently demonstrated a transient decrease in cardiac phosphocreatine (PCr)/ATP with handgrip stress, indicative of ischemia, in women with chest pain but no artery disease. The most likely explanation for these results was the presence of microvascular disease. Thus, given the sensitivity of changes in bioenergetics to ischemia and the lack of any direct, non-invasive measurements of microvascular disease, we will use 31P-NMR spectroscopy to evaluate the effects of diabetes on cardiac metabolism. Specifically, we will test the hypothesis that patients with diabetes will exhibit reversible, exercise-induced decreases in PCr/ATP and PCr/inorganic phosphate consistent with an imbalance in energy supply and demand. Furthermore, we propose that these changes will be present only in those diabetic patients with evidence of systematic microvascular disease and will be accompanied by evidence of contractile dysfunction as assessed by cine MRI. Finally we anticipate that
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the observation of metabolic functional abnormalities will be predictive of short- and long-term outcomes. We will test these hypotheses by determining the effects of handgrip exercise on cardiac bioenergetics and cardiac function in diabetic patients with and without evidence of systematic microvascular disease. We will also evaluate the utility of abnormal cardiac bioenergetics and function as predictors for the development of overt cardiac disease in patients with diabetes. Cardiac bioenergetics will be assessed using 31P-NMR spectroscopy at 4.1T and cardiac function will be measured using cine MRI at 1.5T. Type 1 diabetic patients aged 40 and under with a duration of diabetes greater than 10 years will be studied and grouped based on the presence or absence of systemic microangiopathy. These studies will enable us to assess whether the presence of microvessel disease is a prerequisite for the development of cardiac dysfunction in diabetic patients. This investigation will provide an unprecedented insight into the impact of diabetes on cardiac function and bioenergetics in humans. This will provide valuable information for the development of novel therapeutic interventions and improved management of diabetic patients with cardiac disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSTABILITY
PROPERTIES
AND
DETERMINANTS
OF
GAA
REPEAT
Principal Investigator & Institution: Bidichandani, Sanjay I.; Biochem and Molecular Biology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Friedreich ataxia is an autosomal recessive disease, characterized clinically by ataxia (incoordination), cardiomyopathy and diabetes. The most common mutation, seen in >95% of patients is an abnormal expansion of a GAA triplet-repeat sequence in intron 1 of the FRDA (frataxin) gene. Normal and mutant alleles contain 6 - 100 and 100 - 1700 triplets, respectively. Expanded (mutant) alleles exhibit marked instability in somatic cells and during intergenerational transmission. Disease-causing expansions arise when premutation alleles (30 - 100 triplets) undergo hyperexpansion during intergenerational transmission. The mechanism of hyperexpansion of premutation alleles and the subsequent somatic and germline instability of expanded alleles remains poorly understood. The overall goal of this project is to investigate the mutagenic mechanisms underlying the genetic instability of the GAA triplet-repeat sequence. We will perform "small-pool PCR" (SP-PCR) analysis to test the pattern of genetic instability of normal, premutation, and expanded chromosomes, in a wide variety of somatic tissues and germ cells derived from patients and asymptomatic carriers of various alleles. We will investigate the effect of DNA replication on GAA triplet-repeat instability using a defined eukaryotic replication model system. We will also investigate the role of cis-acting and epigenetic modifiers in determining instability of the GAA triplet-repeat sequence. It is hoped that these studies will lead to the development of novel strategies to prevent or reverse the process of GAA triplet-repeat expansion as a possible future therapy for Friedreich ataxia. Our data could potentially lead to the discovery of general properties of triplet-repeat instability, which will have implications for other diseases caused by this mutational mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF NA,K ATPASE BY THE AH RECEPTOR Principal Investigator & Institution: Walker, Mary K.; Associate Professor of Pharmacology And; None; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 05-AUG-2000; Project End 31-JUL-2004 Summary: Human exposure during pregnancy to persistent environmental pollutants, like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related chemicals, results in decreased birth weights, neurological deficits, thyroid hormone alterations, lung auscultation, and hyperpigmentation. The mechanism by which TCDD mediates developmental toxicity has not been elucidated. The basic helix-loop-helix-PAS transcription factor, aryl hydrocarbon receptor (AhR), is required for TCDD-induced teratogenicity in mice and likely mediates teratogenicity in other species. TCDD toxicity may result from alterations in gene transcription by the AhR. One potential AhR gene target that could account for some of TCDD's teratogenic effects is the Na+/K+ ATPase alpha1. Putative dioxin response elements are conserved in the 5' enhancer region of the mammalian and avian Na+/K+ ATPase alpha1 gene. In the chick embryo, TCDD reduces myocardial Na+/K+ ATPase alpha1 protein expression, induces a dilated cardiomyopathy, and alters ECGs, all consistent with reduced Na+/K+ ATPase activity. In mice lacking the AhR, embryos develop a hypertrophic cardiomyopathy and cardiac fibrosis which worsens with age, consistent with the potential overexpression of Na+/K+ ATPase alpha1 and development of hypertension. I will use the chick embryo and AhR null mice to test the hypothesis that the AhR regulates myocardial expression of the Na+/K+ ATPase alpha1 gene, altering cardiovascular development. The aims of this proposal are to (1) elucidate the regulation of myocardial Na+/K+ ATPase alpha1 gene in AhR null mice and in the developing chick embryo by TCDD using RT-PCR, and in vitro by promoter analysis of the avian gene; (2) determine the tissue significance of this regulation by quantitating myocardial ouabain binding sites and Na+/K+ ATPase enzyme activity in AhR null mice and TCDD-exposed chick embryos; (3) determine the functional significance by measuring blood pressure in AhR null mice and myocardial sensitivity to ouabain in TCDD-exposed chick embryos by ECG; and (4) analyze the expression of murine and avian homologues of candidates genes, whose expression is altered by TCDD in the rat embryo heart and lung as identified by Dr. Selmin, University of Arizona, by PCR-selected subtractive hybridization method and screening of gene microarrays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF BETA-RECEPTOR SIGNALING IN CARDIOMYOPATHY Principal Investigator & Institution: Bernstein, Daniel; Professor of Pediatrics; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: The cardiac responses to stress and cardiomyopathy share a common feature: altered signaling through G protein-coupled receptor (GPCR) pathways that regulate the homeostatic balance of signaling in the heart. This altered signaling can result from changes in the expression or function of receptors, G proteins, as well as down-stream effectors. Restoration of normal homeostasis in cardiomyopathy via GPCR signaling is the basis for medical therapies that target GPCRs, such as the beta-adrenergic receptor (AR). The goal of this proposal is to study the specific roles of beta1 and beta2-ARs in the pathophysiology of cardiomyopathy. Alterations in beta-AR signaling are a central manifestation of chronic sympathetic activation. However, there is controversy as to
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whether beta-AR downregulation is responsible for the decrease in heart function or is a mechanism to protect the heart from chronic sympathetic stimulation. Recent evidence has linked beta-AR signaling not only to alterations in cardiac function, but to mitogenic pathways which could play a role in cardiac remodeling. We have developed an ideal model to examine the role of beta-ARs in cardiomyopathy: mice with targeted disruptions of beta1 and beta2-ARs. We have preliminary evidence suggesting that absence of the beta1-AR may attenuate the development of cardiomyopathy. Further evidence suggests that absence of the beta2-AR may exacerbate the cardiotoxicity of chronically administered catecholamines. We will utilize our knockout models: 1) To determine the role of beta-ARs in the pathogenesis of cardiomyopathy and whether total absence of beta1 and/or beta2-ARs will attenuate or accelerate cardiac dysfunction in models of cardiomyopathy; 2) To determine whether differences between beta1 and beta2-AR subtypes, both in their role in normal physiology and in their contribution to the cardiomyopathic phenotype, are related to differences in regulated expression or to differences in primary structure. For this purpose, we will utilize a gene exchange model, in which the murine beta1-AR is replaced with a murine beta2-AR under control of the native beta1-AR promoter; 3) To determine the role of beta-AR-mediated interactions between cardiac myocytes and fibroblasts in the pathogenesis of cardiomyopathy; 4) To identify signaling events, mediated by both classical (GS) and alternative (non-GS) pathways, that are altered in cardiomyopathy, and to determine the role of beta-ARs in regulating these pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECIALIZED CENTER OF RESEARCH IN HEART FAILURE Principal Investigator & Institution: Mann, Douglas; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 17-FEB-1995; Project End 31-JAN-2005 Summary: The overall objective of the current SCOR and the Proposed Renewal is to elucidate the molecular basis for the long-term adaptive response of the heart to injury, both inherited and acquired, where manifested by hypertrophy or dilitation. This proposal encompasses 5 collaborative investigations, supported by integrated core facilities to address issues fundamental to the etiology, pathogenesis and treatment of cardiac failure. Novel genes will be identified responsible for inherited cardiac disorders, familial dilated cardiomyopathy (FDCM) manifested in the left ventricle and arryhthmogenic right ventricular dysplasia in the right ventricle, as paradigms of dilated cardiomyopathy, the most common form of acquired heart failure. To date, two genes (cytoskeletal) have been identified that cause DCM, actin and desmin. Thus, cytoskeletal proteins may provide a unifying causality for DCM analogous to that of sarcomeric proteins for HCM. Accordingly, insight gained from expression of the mutant desmin in the transgenic mouse should have pathogenetic implications for DCM due to other defective cytoskeletal proteins, whether familial or acquired. While assembly and organization of the cytoskeletal components are an integral part of the cardiac growth response, their role as heretofore been ignored until the identification of the integrin signaling pathway (RhoA, Focal Adhesion Kinase, and Integrin Linked Kinase). In Dr. Schwartz' project, dominant negative mutants of these molecules will be used in cardiac myocytes and Gene-Switch transgenics to determine whether one or all of these are necessary for cytoskeletal assembly and hypertrophy. FHCM, due to over 100 mutations in seven genes, develops the secondary phenotype of increased fibrosis and hypertrophy, providing the opportunity for prevention. Renin-angiotensin system (RAS) inhibitors will be assessed in transgenics harboring the human cTNT mutation
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and, in preparation for future gene therapy, Gene-Switch will be used to determine if the phenotype is reversible. Growth factor(s) responsible for the secondary phenotype will be sought through subtraction hybridization. A novel pathway (TNFalpha) shown in the current SCOR to play a pivotal role in the growth response (hypertrophy) and heart failure (apoptosis), will be pursued to identify molecular interaction with RAS, both in genetic models and in patients with heart failure and to develop novel specific therapies. Strategies to achieve the aims, will utilize "state of the art" techniques: automated genetic analyzers for genotyping and DNA sequencing, BACs, YACs, and DNA microchip arrays to identify genes, the RU-486 Gene Switch to regulate expression of transgenes, PCR-generated dominant negative mutants, "gutless" tetracycline dependent adenoviral vectors, selective elimination of genes (knock-out mice), and Ta178 radionuclide angiography to assess mouse cardiac function. These studies elucidate further the molecular foundations of cardiac hypertrophy and failure and should provide a rational basis for more effective therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECIALIZED CENTER OF RESEARCH IN HEART FAILURE Principal Investigator & Institution: Seidman, Christine W.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-JAN-1995; Project End 31-JAN-2005 Summary: Heart failure is a leading cause of disability and death in the U.S. affecting at least 4.7 million individuals, with an estimated 400,000 new cases each year. Progress in the prevention and treatment of heart failure has been limited in magnitude due in some part to an incomplete understanding of basic biologic phenomena and mechanisms that underlie the clinical syndrome. This Heart Failure SCOR proposal attacks the problem across a spectrum of basic to clinical studies. The theme unifying these studies is that heart failure is a continuum of molecular phenomena and cellular mechanisms. These direct the progression from an underlying cause, such as a single nucleotide substitution in the DNA of an individual with familial dilated cardiomyopathy-to the multiple disturbances of cell and organ function and regulation that comprise the clinical syndrome of heart failure, irrespective of the initial inciting cause. The participating Project Leaders have an extensive record of produce collaboration and have focused their efforts on five interactive projects with substantial efforts of interface. Dr. C. Seidman's project seeks to identify genetic causes of inherited dilated cardiomyopathy with the expectation that during the next granting period a common theme will emerge that explains the significant genetic heterogeneity of this condition. Dr. (Michel) Project seeks to define the role of the interactions between caveolae and myocyte signaling proteins that evolve during the development and progression of heart failure. Project 3 (Ingwall) combines biophysical, biochemical and molecular biologic tools to test the hypothesis that decreased energy reserve via the creatine kinase system impairs contractile mutated G/a0 subunits that develop dilated cardiomyopathy with compensatory hypertrophy. These die of heart failure within two months. Pathways that link transgene expression to heart failure in these mice will be defined. Dr. Seidman's project has developed two genetically engineered lines of mice that are models of familial hypertrophic cardiomyopathy; these mice will be studied to determine those factors that worsen cardiac hypertrophy and in some, cause dilated cardiomyopathy and heart failure. All projects will interact closely with Core B (Mende and Lee), which has the technology to prepare and characterize contractile function of individual myocytes as well as to obtain non-invasive imaging of murine and human hearts to evaluate cardiac function. Cardiac histology, immunohistochemistry and in situ
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hybridization will be provided by CORE c (Schoen) to evaluate gene expression in the myocardium. In all of these interactive projects, the collaborating fundamental biological phenomena and mechanisms that bear on improved prevention and treatment of patients at risk. The aggregate productivity of coordinated project efforts has already exceeded the expectations of the individual components and we anticipate that these benefits will expand even further during the next granting period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEROL BIOSYNTHESIS IN TRYPANOSOMATID PARASITES Principal Investigator & Institution: Buckner, Frederick S.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: The long-term objective of this project is to discover new therapeutics for leishmaniasis and Chagas disease. These infectious diseases are caused by parasitic protozoa of the family, Trypanoisomatidae. Leishmaniasis affects 12 million people in 88 countries with an annual incidence of about 2 million people. Visceral leishmaniasis is fatal if untreated and cutaneous leishmaniasis causes serious morbidity, Chagas disease is caused by Trypanosoma cruzi and is endemic in over 20 countries in Latin America. An estimated 16-18 million persons are chronically infected and at risk for developing life threatening cardiomyopathy or megasyndromes of the gastrointestinal tract. The treatments for leishmania infections are inadequate because of the toxicity of currently available drugs and because of the need to administer the drugs by injection. Treatments for Chagas diseases are highly toxic and do not cure most patients with chronic phase disease. Leishmania species and Trypanosoma cruzi synthesize membrane sterols similar to those of fungi. It has been shown that a number of anti-fungal drugs that act on sterol biosynthesis or directly on ergosterol have anti- lishmanial and antitrypanosomal effects. Our hypothesis is that a characterization of the sterol biosynthesis pathway in Trypanosomatids will lead to novel drug treatments. The specific aims of the research are: 1) Clone Trypanosomatid homologs of selected sterol biosynthesis genes. We will concentrate on five enzymes that are potentially enzymes that are potentially excellent drug targets: squalene synthetase, squalene epoxidase, C14 demethylase, delta 14-reductase, and C8 isomerase. Genes will be cloned with the use of sequences in the parasite genome databases that have high homology scores to sterol biosynthesis genes of other organisms. 2) Characterize the Trypanosomatid homologs of sterol biosynthesis genes. The enzymatic function of the cloned parasite genes will be investigated by heterologous complementation of yeast mutants. We will be prepared for the possibility that Trypanosomatids make sterols by a route that differs from the yeast pathway. 3) Interrupt the sterol biosynthesis genes in Leishmania mexicana and Trypanosoma cruzi. Targeted knockout of sterol biosynthesis genes will be done using selectable drug markers. The enzymes that are shown to be essential for parasite viability will be prioritized for subsequent drug studies. 4) Screen sterol biosynthesis inhibitors for anti-Trypanosomatid activity. Test compounds will be obtained from collaborating investigators and pharmaceutical companies. Drugs will be screened in high throughput in vitro systems. The best compounds will be tested in murine models of Chagas disease and leishmaniasis. The drugs discovered in this research program will hopefully provide better future treatment for patients with these devastating diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURAL GENOMICS OF NOREPINEPHRINE TRANSPORTERS Principal Investigator & Institution: Blakely, Randy D.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The antidepressant-sensitive norepinephrine (NE) transporters (NETs) constitute the major mode of synaptic inactivation of NE. Recent clinical genetic studies by our groups identified a coding mutation, A457P, in one NET allele of a proband with Orthostatic Intolerance (OI) presenting with reduced NE clearance, increased spillover and reduced intraneuronal NE metabolism. The A457P mutation was found to track with measures of postural tachycardia in the proband?s family and to correlate with altered synaptic NE metabolism. In Specific Aim 1, we propose to ascertain the functional impact of the A457P and other identified NET coding mutations in terms of transport and efflux, transporter trafficking and surface expression using heterologous expression systems. Evidence will be sought to support a dominant-negative interaction between mutant and wildtype subunits and whether homomultimeric complexes support NET function. In Specific Aim 2, we propose to extend our genetic evaluation of NET deficiency to evaluate additional subjects with OI and cardiomyopathy (CM) using high-throughput gene scanning techniques. These studies will focus on the NET coding exons and splice junctions and also include a recently identified intronic region that plays a critical role in NET gene expression. Methods will be implemented to allow for an evaluation of altered NET protein in biopsies tissue. Finally, attention and mood are dependent on proper noradrenergic signaling in the CNS and symptoms are present in our A457P probands indicating attention deficit, anxiety and hyperarousal. Thus, we propose in Specific Aim 3 to examine NET alleles with primary diagnoses of attention-deficit hyperactivity disorder (ADHD), attentional deficit (ADD) subtype and Major Depression, melancholic subtype, which is characterized by hyperarousal and anxiety. We will select subjects for analysis in both cases on the basis of comorbid tachycardia. Together these studies offer an opportunity for a better understanding of the molecular and behavioral manifestations of genetic NET variation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TARGETED ALTERATION OF ACTIN IN THE HEART Principal Investigator & Institution: Lessard, James L.; Professor and Associate Director; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-JAN-1997; Project End 31-MAR-2006 Summary: (provided by applicant): The overarching goal of this research proposal is to understand how the heart responds to alterations in actin, the principal component of thin filaments involved in generating contractile force by the heart. Our previous work strongly supports the hypothesis that the conserved structural differences between cardiac actin and enteric actin are related to unique functional differences between these two proteins. Here, we hypothesize that differences between cardiac actin and enteric actin at position 1 (D->-) and/or position 360 (Q->P) will account for the functional alterations. Thus, the effect of these amino acid alterations in cardiac actin will be assessed in terms of structural, molecular, and physiological changes in the myocardium. We also have transgenically introduced two mutant cardiac actins (R312H and E361G) into the mouse heart that are associated with idiopathic dilated cardiomyopathies in humans and another (A295S) which is associated with hypertrophic cardiomyopathy. This approach will permit us to define the progression of
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the aberrant phenotype, if any, and provide insights into the pathogenesis associated with these mutations. We will also determine whether increased expression of skeletal or vascular actin is required for survival of cardiac actin-deficient mice. The hypothesized requirement for skeletal and vascular actin for survival of cardiac actin null animals to birth and beyond will be tested using mice that are cardiac actin null and skeletal actin null or vascular actin null. The impact of a deficiency in skeletal actin or vascular actin on the survival of cardiac actin heterozygotes will also be of interest. Finally, we plan to seek out modifier loci that affect the survival of cardiac actin heterozygotes. We have recently obtained evidence suggesting that there is a marked strain-specific variation in survival of mice that are heterozygous for the null cardiac actin allele. A reciprocal back-cross strategy will be applied and genes that modify the survival phenotype will be sought using a genome-wide scan for linkage. These approaches will provide new insights into the pathogenesis of heart failure in this model and, in future studies, hopefully permit the identification of candidate genes that affect survival in human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE CYTOSKELETON IN HAART-INDUCED CARDIOMYOPATHY Principal Investigator & Institution: Bowles, Neil E.; Instructor; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): One of the consequences of the development of improved therapies for the treatment of HIV infection and the acquired immunodeficiency syndrome, and the associated longer survival of infected patients, has been the emergence of diseases such as myocarditis and/or dilated cardiomyopathy (DCM). A number of etiological agents have been proposed to be responsible for the initiation of the pathologic processes leading to the development of myocarditis and DCM in HIV-infected patients. These have included infection of myocytes with HIV or cardiotropic viruses, or cardiotoxicity resulting from drugs commonly used by AIDS patients, such as AZT. Monotherapy with AZT is uncommon today because highly active antiretroviral therapy (HAART) is a formidable clinical combination. However, AZT has been reported to cause a mitochondrial skeletal myopathy, similar to inherited skeletal myopathies, as well as myopathies secondary to inherited cardiomyopathies. Dystrophin was identified as the gene responsible for cardiomyopathy in patients with X-linked cardiomyopathy (XLCM). Dystrophin is thought to provide structural support for the myocyte and cardiomyocyte membrane. Mutations in dystrophin or dystrophin associated protein subcomplexes result in a wide spectrum of skeletal myopathy and/or cardiomyopathy in humans and animal models such as the mouse or hamster. We have recently shown in patients with DCM or ischemic cardiomyopathy that dystrophin remodeling is a useful indicator of left ventricular function. It has been reported that the 2A protease of Coxsackievirus B3, a major etiologic agent of acquired DCM, is capable of cleaving dystrophin, resulting in sarcolemmal disruption in infected mouse hearts. Further, in murine models of DCM defects in the integrity of dystrophin and/or other components of the cytoskeleton may be important in disease pathogenesis in these models. In order to further delineate the role of cytoskeletal disruption in models of acquired DCM we are proposing the following specific aims: Specific Aim 1: Delineation of the events leading to disruption of the cytoskeleton in transgenic mice. Specific Aim 2: Characterization of the cytoskeleton in HAART-treated transgenic mice. Specific Aim 3: Role of extrinsic stimuli in the development of HAART-induced cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Cardiomyopathy
Project Title: THE EXERCISE PRESSOR REFLEX IN CARDIOMYOPATHY Principal Investigator & Institution: Garry, Mary G.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 13-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Diminished exercise capacity with increased shortness of breath and fatigue are major causes of morbidity in cardiomyopathic patients. Studies suggest that the exaggerated cardiovascular responses to exercise in heart failure patients are mediated, in part, by an over active exercise presser reflex (EPR). The EPR is a mechanism where blood pressure and heart rate increase in response to contraction-induced activation of primary afferent neurons and reflexive changes in autonomic outflow. The existence of an over active EPR in heart failure is also supported by the cardioprotective effects of sympathetic blockade in cardiomyopathic disease. In spite of these compelling clinical findings, however, the lack of an animal model in which the EPR and heart failure can be studied simultaneously has limited our understanding of the mechanisms involved in the evolution of reduced exercise capacity and abnormal circulatory control in heart failure. We have described a novel rat model in which significant increases in blood pressure and heart rate are reliably observed in response to static muscle contraction and passive stretch. Additionally, the EPR is exaggerated in rats with cardiomyopathy following coronary artery ligation. Finally, we demonstrate a molecular dysregulation of skeletal muscle afferent neurons during cardiomyopathy in the rat. The specific aims of this proposal are: Specific Aim #1: Compare the effect of activation of skeletal muscle primary afferent neurons on the EPR in normal animals and in ligated animals at defined intervals during cardiomyopathy. Specific Aim #2: To determine the differential contribution of metabolically vs. mechanically-sensitive skeletal muscle afferent neurons to the EPR in the normal and cardiomyopathic states. Specific Aim #3: Evaluate the spinal pharmacology and molecular dysregulation of the exaggerated EPR. With this model, we will evaluate the contribution of the EPR to circulatory control during cardiomyopathy and provide a multidisciplinary evaluation of circulatory regulation during exercise in cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF NUCLEAR LAMINS IN MUSCLE DISEASE Principal Investigator & Institution: Burke, Brian; Professor; Anatomy and Cell Biology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2007 Summary: (provided by applicant): A-type and B-type nuclear lamins form a family of nuclear envelope proteins that have an essential function in the maintenance of nuclear structure. Mutations in the human lamin A gene have been linked to several diseases which include Emery-Dreifuss muscular dystrophy (EDMD) and cardiomyopathy. Since the A-type lamins are found in majority of adult cell types it is extremely puzzling that defects in these proteins should be associated primarily with muscle specific disorders. The goal of this proposal is to elucidate the roles that individual lam in family members play in the organization of the cell nucleus and how in particular this relates to the maintenance of muscle integrity. The proposal will take advantage of mouse strains harboring targeted mutations in lamin genes, including a strain in which the lamin A gene has been deleted and which develops a disorder that closely resembles human EDMD. Inactivation of B-type lamin genes as well as the introduction of specific human disease-linked point mutations into the mouse lamin A gene will provide novel insight
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into the role of individual lamin proteins in nuclear organization and how this relates to disease processes in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEINS
THIN
FILAMENTS
WITH
CARDIOMYOPATHIC
MUTANT
Principal Investigator & Institution: Tobacman, Larry S.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 15-JAN-2000; Project End 31-DEC-2003 Summary: (adapted from the applicant's description): Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disorder caused by mutations in any of several genes encoding the proteins of the cardiac contractile apparatus. This project will characterize the effects of FHC-causing mutations on the in vitro function of the various thin filament proteins so far implicated in this disorder: troponin T, troponin 1, and alpha-tropomyosin. By comparing normal and mutant proteins, the project will provide some of the insight required to understand the pathophysiology of cardiac disease in these patients. Also, the applicant will use the mutations to test the mechanism by which cardiac contraction is regulated by troponin and tropomyosin. A multi-faceted study of the mutant proteins is planned, with examination of several protein-protein affinities (including thin filament binding of troponin, of troponintropomyosin, and of myosin Sl; troponin binary subunit interactions; effects of calcium and of myosin on these various processes), calcium affinity, myosin MgATPase regulation, folding stability, in vitro motility, in vitro force, and structural effects on the regulatory conformational switching of the thin filament as determined by 3-D reconstructions of electron micrographs. A smaller number of mutations, identified in the cardiac actin gene, have been found causative in a subset of patients with another genetic disorder: dilated cardiomyopathy. Mutant forms of actin will be similarly examined for alterations in interactions with tropomyosin and troponin. (1) FHC mutations occurring in two regions of troponin T will be investigated. Troponin T mutants R92Q, R92W, Al 04V, and Fl 01 I occur in or near a region of troponin T that the applicant recently identified as forming a critical portion of the troponin tail. In a different region, the effects of FHC-linked COOH-terminal truncation of 28 residues will be studied. (2) Six troponin I mutations that occur in FHC will be similarly investigated, all located in the region of troponin I that interacts with the regulatory domain of troponin C. (3) Five FHC-linked tropomyosin mutants will be created and similarly studied, as will an actin mutation that causes inherited dilated cardiomyopathy and that is hypothesized to interact abnormally with tropomyosin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TISSUE RENIN ANGIOTENSIN/CHYMASE SYSTEM IN HEART FAILURE Principal Investigator & Institution: Dell'italia, Louis J.; Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-1995; Project End 31-JAN-2006 Summary: (the applicant's description verbatim): The PI has studied the role of the cardiac renin angiotensin system (RAS)/chymase system in mechanisms of angiotensin II (ANG II) formation in the heart in response to volume overload heart failure. These studies demonstrated increased expression of RAS and chymase in the dog heart associated with LV dilatation (decreased wall thickness/diameter ratio), increased
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Cardiomyopathy
matrix metalloproteinase (MMP) activity, and dissolution of the fine collagen weave. Neither suppression of tissue ANG II with ACE inhibitor, nor blockade of the AT1 receptor modulated this remodeling process. Further, heterozygote ACE knockout mice (1/0), having 40 percent of tissue ACE activity compared to wild type, had a significantly lower w/t diameter ratio than wild type mice in response to volume overload. There was a failure to downregulate LV MMP activity in the 1/0 mice vs. 1/1 mice and in dogs with chronic MR. In both animal models, chymase activity was upregulated and not effected by blockade of the RAS. There is recent compelling evidence that remodeling of the extracellular matrix (ECM) is regulated by MMPs in dilated cardiomyopathy. Inhibition of tissue ACE, by its effect of decreasing ANG II and increasing bradykinin (BK), can promote MMP synthesis and activation. In addition, chymase can also directly cleave and activate MMPs. Thus, the hypothesis of the current proposal is that tissue concentrations of ACE and chymase mediate the LV remodeling pattern in response to volume overload by their influence on myocardial MMP activational state. The PI will measure interstitial fluid (ISF) ANG II, BK, and MMP activational state in the conscious rat (low chymase/ACE activity ratio) and hamster (high chymase/ACE activity ratio) in response to volume overload stress. This approach combined with targeted transgenic models of variable ACE expression and increased chymase expression will relate in-vivo LV function and collagen weave by scanning EM to MMP activation. Viral vectors for chymase antisense will be utilized in the heart failure models in the rat, hamster, and mouse. In the absence of an orally effective chymase inhibitor, this approach will answer important questions regarding the physiological importance of the relative concentrations of ACE and chymase in LV remodeling in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCRIPTIONAL DEVELOPMENT
REGULATION
OF
CARDIOMYOCYTE
Principal Investigator & Institution: Huggins, Gordon S.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2002; Project Start 25-SEP-1995; Project End 31-JUL-2004 Summary: (the applicant's description verbatim): The normal development of the cardiovascular system is regulated by a complex set of molecular pathways that interpret environmental and developmental signals into changes in cardiovascular gene expression. Perturbations of these signaling pathways have been implicated in a number of prevalent human cardiovascular diseases including congenital cardiac malformations, pathologic cardiac hypertrophy, and dilated cardiomyopathy. During the last ten years we have studied the nuclear transcription factors that regulate the development and function of the mammalian cardiovascular system. In an initial series of experiments we identified a cardiac-specific transcriptional promoter/enhancer in the 5' flanking region of the cardiac troponin C (cTnC) gene. We used this promoter to identify a set of nuclear transcription factors that appear to play important roles in regulating early cardiomyocyte development and cardiac morphogenesis. Among these was the GATA4 zinc finger protein that binds to and trans-activates a wide variety of cardiac specific transcriptional regulatory elements. Using a gene targeting approach we showed that GATA4 is necessary for the formation of the primitive ventral heart tube during early murine embryogenesis. More recently, we identified a second zinc finger protein called cardiac friend of GATA (CFOG) that is expressed in the developing heart and that binds specifically to the N-terminal zinc finger of GATA4. Similarly, Olson and coworkers recently demonstrated that GATA4 also interacts with the rel-related protein NFAT3
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and that these two proteins appear to be important regulators of cardiac myocyte hypertrophy. The long term goal of the studies described in this continuing RO1 proposal is to understand the molecular mechanisms by which GATA proteins, in conjunction with other transcriptionfactors and coactivator/ repressor proteins regulate cardiogenesis and cardiac hypertrophy. Specifically we will (1) map the regions of GATA4 that are required for its central role in the heart tube formation. (2) genetically and biochemically characterize the interaction between GATA4 and CFOG and understand the effects of this interaction on the transcriptional activity of GATA4, (3) Use gene targeting to determine the roles of NFAT3 and CFOG in cardiac development and function in the mouse. Together, the results of these studies should provide novel basic insights into the molecular pathways that regulate normal cardiac development and function. They should also be relevant to understanding the molecular pathophysiology of a number of clinically important inherited and acquired cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRIGLYCERIDE SYNTHESIS AND LIPOTOXICITY Principal Investigator & Institution: Farese, Robert V.; Associate Investigator; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The obesity epidemic is threatening world health, largely because of its associated diseases, type 2 diabetes mellitus and atherosclerosis. Although the mechanisms underlying obesity-associated diseases are unclear, the lipotoxicity hypothesis has emerged as a plausible explanation. This hypothesis states that the deposition of excess lipids in tissues other than white adipose tissue over time leads to tissue dysfunction. For example, lipid deposition in skeletal muscle is associated with insulin resistance, in pancreatic beta cells with defective insulin secretion, and in heart muscle with cardiomyopathy. Despite these strong associations from studies in animals and humans, the lipotoxicity hypothesis remains unproven, and its underlying mechanisms remain unclear. Whether triglycerides themselves or precursors of triglyceride synthesis (e.g., diacylglycerol and fatty acyl CoAs) are toxic to nonadipose cells is unclear. We propose to test the lipotoxicity hypothesis by directly modulating triglyceride synthesis in specific tissues of mice. Triglyceride synthesis is catalyzed by acyl CoA:diacylglycerol (DGAT) enzymes. Aim 1 describes the generation and analysis of mice that overexpress DGAT1 in skeletal muscle, pancreatic beta cells, and cardiac muscle. Aim 2 describes the generation and analysis of mice that lack DGAT1 in skeletal muscle, beta cells, and white adipose tissue. We will use these mouse models to determine whether modulating triglyceride synthesis influences tissue lipotoxicity and to explore the mechanisms, including alterations in tissue lipids, gene expression, and signaling pathways, that contribute to lipotoxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TROPOMYOSIN CONTRACTION
AND
THE
REGULATION
OF
MUSCLE
Principal Investigator & Institution: Lehrer, Sherwin S.; Senior Scientist; Boston Biomedical Research Institute 64 Grove St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 01-APR-1978; Project End 31-JAN-2005 Summary: (Verbatim from the applicant's abstract) The broad, long-term objective is to elucidate the molecular basis of the regulation of muscle contraction by defining the role
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of each muscle component: actin, tropomyosin (Tm), the troponin components, TnI, TnT, TnC, and myosin. Health Relatedness: This information will help in the understanding of muscle diseases e.g., hypertrophic cardiomyopathy resulting from mutations in Tm, TnT, TnI and myosin and stunned myocardium resulting from coronary artery disease. Tm, in its interaction with actin, plays a key role in determining the equilibria between the 3 states of the muscle thin filament, Blocked/Closed/Open (contraction takes place in the Open state). By interacting with actinTm, the troponin complex and myosin heads change the equilibrium between the states, thereby turning contraction on and off. The specific aims are to test the hypotheses that: (a) Ca2+ and myosin induce changes in position and conformation of Tm on actin which results in a shift of the equilibrium toward the Open biochemical state, thereby allowing contraction; (b) in the absence of Ca2+, TnI, interacts with Tm in addition to actin, to stabilize the thin filament in the Blocked-state; (c) TnT: (i) inhibits actinTm-S1 ATPase by altering Tm conformation, (ii) increases the cooperativity between actinTm units, (iii) interacts differently with Tm in each of the 3 biochemical states; (d) Tm movement to the thin filament On-activity state (Open-state) occurs during myosin binding after Ca2+induced TnI dissociation from actin; (e) the two heads of HMM act cooperatively to shift actinTm from the Closed to the Open-state; (f) mutants of Tm found in patients with FHC alter the equilibria between the 3 biochemical states of the thin filament thereby affecting contraction. Methods: In addition to characterization of the 3 states in solution with ATPase, myosin titrations and stopped-flow techniques, extensive use will be made of high resolution distance measurements between components with timeresolved fluorescence energy transfer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: XANTHINE OXIDASE, MYOCARDIAL GENOMICS AND HEART FAILURE Principal Investigator & Institution: Cappola, Thomas P.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by the applicant):Cardiac hypertrophy is a central pathologic feature of congestive heart failure. Prior investigations suggest that oxidative stress induces the expression of hypertrophy genes in vitro, and may be an important cause of cardiac hypertrophy in humans. The applicant proposes to merge his interest in clinical investigation with state-of-the-art genomic approaches to determine how oxidative stress promotes cardiac hypertrophy in humans. Based on preliminary data, he will focus on xanthine oxidase as a source of myocardial oxidative stress. The central thesis of this proposal is that increased myocardial XO contributes to heart failure by stimulating the transcription of hypertrophy genes. In Aim 1, the applicant will use Affymetrix microarrays to determine genes associated with hypertrophy in failing explanted human myocardium. Multiple analytic approaches will be used, including a hypothesis-based analysis of pre-selected candidate genes, exploratory analyses, and global analyses of patterns in gene expression. In Aim 2, the applicant will demonstrate that myocardial XO activity correlates with expression of these hypertrophy genes in humans. In Aim 3, the applicant will test the hypothesis that XO inhibition with allopurinol attenuates the expression of hypertrophy genes in serial endomyocardial biopsies, and prevents an increase in cardiac mass in patients with dilated cardiomyopathy. These experiments will determine the transcriptional targets of XO in human myocardium, thereby clarifying the role of oxidative stress in heart failure. Moreover. they are the first steps in determining whether XO inhibition is a novel
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treatment strategy for heart failure. This research will be performed at the Johns Hopkins Medical Institutions under the mentorship of Dr. Joshua Hare, an expert in the field of oxidative stress in heart failure. Genomic analyses will be performed in collaboration with the HopGene PGAmApplied Genomics in Cardiopulmonary Disease. The applicant's interdisciplinary training, strong mentorship, career development program, supportive environment, and novel research plan will give him the experience and tools he needs to develop into a highly successful, independent clinical investigator. 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 “cardiomyopathy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for cardiomyopathy in the PubMed Central database: •
A critical role for PPAR[alpha]-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content. by Finck BN, Han X, Courtois M, Aimond F, Nerbonne JM, Kovacs A, Gross RW, Kelly DP.; 2003 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=298755
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A Familial Hypertrophic Cardiomyopathy Locus Maps to Chromosome 15q2. by Thierfelder L, MacRae C, Watkins H, Tomfohrde J, Williams M, McKenna W, Bohm K, Noeske G, Schlepper M, Bowcock A, Vosberg H, Seidman JG, Seidman C.; 1993 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46910
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Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. by Yamamoto S, Yang G, Zablocki D, Liu J, Hong C, Kim SJ, Soler S, Odashima M, Thaisz J, Yehia G, Molina CA, Yatani A, Vatner DE, Vatner SF, Sadoshima J.; 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155047
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Apoptosis in heart failure: Release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. by Narula J, Pandey P, Arbustini E, Haider N, Narula N, Kolodgie FD, Dal Bello B, Semigran MJ, Bielsa-Masdeu A, Dec GW, Israels S, Ballester M, Virmani R, Saxena S, Kharbanda S.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22202
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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Both hypertrophic and dilated cardiomyopathies are caused by mutation of the same gene, [delta]-sarcoglycan, in hamster: An animal model of disrupted dystrophinassociated glycoprotein complex. by Sakamoto A, Ono K, Abe M, Jasmin G, Eki T, Murakami Y, Masaki T, Toyo-oka T, Hanaoka F.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28400
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Ca2 +-desensitizing effect of a deletion mutation [Delta]K210 in cardiac troponin T that causes familial dilated cardiomyopathy. by Morimoto S, Lu QW, Harada K, Takahashi-Yanaga F, Minakami R, Ohta M, Sasaguri T, Ohtsuki I.; 2002 Jan 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117405
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Cardiac troponin T and familial hypertrophic cardiomyopathy: an energetic affair. by Schwartz K, Mercadier JJ.; 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=182216
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Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways. by Twu C, Liu NQ, Popik W, Bukrinsky M, Sayre J, Roberts J, Rania S, Bramhandam V, Roos KP, MacLellan WR, Fiala M.; 2002 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137893
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Cardiomyopathy in Irx4-Deficient Mice Is Preceded by Abnormal Ventricular Gene Expression. by Bruneau BG, Bao ZZ, Fatkin D, Xavier-Neto J, Georgakopoulos D, Maguire CT, Berul CI, Kass DA, Kuroski-de Bold ML, de Bold AJ, Conner DA, Rosenthal N, Cepko CL, Seidman CE, Seidman JG.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86719
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Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. by Redfern CH, Degtyarev MY, Kwa AT, Salomonis N, Cotte N, Nanevicz T, Fidelman N, Desai K, Vranizan K, Lee EK, Coward P, Shah N, Warrington JA, Fishman GI, Bernstein D, Baker AJ, Conklin BR.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18317
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Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. by Ozcelik C, Erdmann B, Pilz B, Wettschureck N, Britsch S, Hubner N, Chien KR, Birchmeier C, Garratt AN.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124392
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Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. by Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE.; 2002 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150860
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Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. by Zhao YY, Liu Y, Stan RV, Fan L, Gu Y, Dalton N, Chu PH, Peterson K, Ross J Jr, Chien KR.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123264
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Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C --deficient mice. by Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, Kesteven SH, Michalicek J, Otway R, Verheyen F, Rainer S, Stewart CL, Martin D, Feneley MP, Fatkin D.; 2004 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324538
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Development of murine ischemic cardiomyopathy is associated with a transient inflammatory reaction and depends on reactive oxygen species. by Dewald O,
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Frangogiannis NG, Zoerlein M, Duerr GD, Klemm C, Knuefermann P, Taffet G, Michael LH, Crapo JD, Welz A, Entman ML.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151404 •
Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. by Stypmann J, Glaser K, Roth W, Tobin DJ, Petermann I, Matthias R, Monnig G, Haverkamp W, Breithardt G, Schmahl W, Peters C, Reinheckel T.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122932
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Disruption of the gene encoding the latent transforming growth factor-[beta] binding protein 4 (LTBP-4) causes abnormal lung development, cardiomyopathy, and colorectal cancer. by Sterner-Kock A, Thorey IS, Koli K, Wempe F, Otte J, Bangsow T, Kuhlmeier K, Kirchner T, Jin S, Keski-Oja J, von Melchner H.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=186672
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Elaboration by mammalian mesenchymal cells infected with Trypanosoma cruzi of a fibroblast-stimulating factor that may contribute to chagasic cardiomyopathy. by Wyler DJ, Libby P, Prakash S, Prioli RP, Pereira ME.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260047
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Evidence that Development of Severe Cardiomyopathy in Human Chagas' Disease Is Due to a Th1-Specific Immune Response. by Gomes JA, Bahia-Oliveira LM, Rocha MO, Martins-Filho OA, Gazzinelli G, Correa-Oliveira R.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148818
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Experimental Assessment of the Role of Acetaldehyde in Alcoholic Cardiomyopathy. by Aberle II NS, Ren J.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150386
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Functional analyses of troponin T mutations that cause hypertrophic cardiomyopathy: Insights into disease pathogenesis and troponin function. by Sweeney HL, Feng HS, Yang Z, Watkins H.; 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24386
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Functional Analysis of Myosin Missense Mutations in Familial Hypertrophic Cardiomyopathy. by Straceski AJ, Geisterfer-Lowrance A, Seidman CE, Seidman JG, Leinwand LA.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42994
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Genetic counselling for hypertrophic cardiomyopathy: are we ready for it? by Vosberg HP.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59597
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Genetic modification of survival in tissue-specific knockout mice with mitochondrial cardiomyopathy. by Li H, Wang J, Wilhelmsson H, Hansson A, Thoren P, Duffy J, Rustin P, Larsson NG.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16263
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Genotype, phenotype: upstairs, downstairs in the family of cardiomyopathies. by Chien KR.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151886
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Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. by Haghighi K, Kolokathis F, Pater L,
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Lynch RA, Asahi M, Gramolini AO, Fan GC, Tsiapras D, Hahn HS, Adamopoulos S, Liggett SB, Dorn GW II, MacLennan DH, Kremastinos DT, Kranias EG.; 2003 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153772 •
Idiopathic restrictive cardiomyopathy is part of the clinical expression of cardiac troponin I mutations. by Mogensen J, Kubo T, Duque M, Uribe W, Shaw A, Murphy R, Gimeno JR, Elliott P, McKenna WJ.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151864
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Lamin A/C truncation in dilated cardiomyopathy with conduction disease. by MacLeod HM, Culley MR, Huber JM, McNally EM.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=169171
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Left ventricular decompression through a patent foramen ovale in a patient with hypertrophic cardiomyopathy: a case report. by Ando' G, Tomai F, Gioffre' PA.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324415
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Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. by Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, Seo T, Hu Y, Lutz EP, Merkel M, Bensadoun A, Homma S, Goldberg IJ.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151861
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Magnetic Resonance Imaging of Myocardial Fibrosis in Hypertrophic Cardiomyopathy. by Wilson JM, Villareal RP, Hariharan R, Massumi A, Muthupillai R, Flamm SD.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124756
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Medical therapy versus interventional therapy in hypertropic obstructive cardiomyopathy. by Seggewiss H.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59612
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Missense Mutations in the [beta]-Myosin Heavy-Chain Gene Cause Central Core Disease in Hypertrophic Cardiomyopathy. by Fananapazir L, Dalakas MC, Cyran F, Cohn G, Epstein ND.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46432
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Molecular Basis of Human Mitochondrial Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency Causing Cardiomyopathy and Sudden Death in Childhood. by Strauss AW, Powell CK, Hale DE, Anderson MM, Ahuja A, Brackett JC, Sims HF.; 1995 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40638
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Nephropathic cystinosis associated with cardiomyopathy: A 27-year clinical followup. by Dixit MP, Greifer I.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137602
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Nontransplant Cardiac Surgery as a Bridge to Heart Transplantation in Pediatric Dilated Cardiomyopathy. by Hsu RB, Chien CY, Wang SS, Chu SH.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124763
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Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: Amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters. by Kawada T, Nakazawa M, Nakauchi S, Yamazaki K, Shimamoto R, Urabe M, Nakata J, Hemmi C, Masui F, Nakajima T, Suzuki JI, Monahan J, Sato H, Masaki T, Ozawa K, Toyo-oka T.; 2002 Jan 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117403
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Reversible Alterations in Myocardial Gene Expression in a Young Man with Dilated Cardiomyopathy and Hypothyroidism. by Ladenson PW, Sherman SI, Baughman KL, Ray PE, Feldman AM.; 1992 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49269
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Severe cardiomyopathy in mice lacking dystrophin and MyoD. by Megeney LA, Kablar B, Perry RL, Ying C, May L, Rudnicki MA.; 1999 Jan 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15120
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Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy. by Kunisada K, Negoro S, Tone E, Funamoto M, Osugi T, Yamada S, Okabe M, Kishimoto T, Yamauchi-Takihara K.; 2000 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26660
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Smooth muscle cell --extrinsic vascular spasm arises from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy. by Wheeler MT, Allikian MJ, Heydemann A, Hadhazy M, Zarnegar S, McNally EM.; 2004 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=351323
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Structural Interpretation of the Mutations in the [beta]-Cardiac Myosin that have been Implicated in Familial Hypertrophic Cardiomyopathy. by Rayment I, Holden HM, Sellers JR, Fananapazir L, Epstein ND.; 1995 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42062
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Systolic Compression of Epicardial Coronary and Intramural Arteries in Children with Hypertrophic Cardiomyopathy. by Mohiddin SA, Fananapazir L.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140291
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Targeted Disruption of the Murine Bin1/Amphiphysin II Gene Does Not Disable Endocytosis but Results in Embryonic Cardiomyopathy with Aberrant Myofibril Formation. by Muller AJ, Baker JF, DuHadaway JB, Ge K, Farmer G, Donover PS, Meade R, Reid C, Grzanna R, Roach AH, Shah N, Soler AP, Prendergast GC.; 2003 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156129
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Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. by Braz JC, Bueno OF, Liang Q, Wilkins BJ, Dai YS, Parsons S, Braunwart J, Glascock BJ, Klevitsky R, Kimball TF, Hewett TE, Molkentin JD.; 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155046
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Targeted overexpression of protein kinase C [beta]2 isoform in myocardium causes cardiomyopathy. by Wakasaki H, Koya D, Schoen FJ, Jirousek MR, Ways DK, Hoit BD, Walsh RA, King GL.; 1997 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23178
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The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. by Liao P, Georgakopoulos D, Kovacs A, Zheng M, Lerner D, Pu H, Saffitz J, Chien K, Xiao RP, Kass DA, Wang Y.; 2001 Oct 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59806
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The L-type calcium channel inhibitor diltiazem prevents cardiomyopathy in a mouse model. by Semsarian C, Ahmad I, Giewat M, Georgakopoulos D, Schmitt JP, McConnell BK, Reiken S, Mende U, Marks AR, Kass DA, Seidman CE, Seidman JG.; 2002 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150949
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The V122I cardiomyopathy variant of transthyretin increases the velocity of ratelimiting tetramer dissociation, resulting in accelerated amyloidosis. by Jiang X, Buxbaum JN, Kelly JW.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64963
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Transient cardiac expression of constitutively active G[alpha]q leads to hypertrophy and dilated cardiomyopathy by calcineurin-dependent and independent pathways. by Mende U, Kagen A, Cohen A, Aramburu J, Schoen FJ, Neer EJ.; 1998 Nov 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24952
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Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride. by Roe CR, Sweetman L, Roe DS, David F, Brunengraber H.; 2002 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151060
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Unusual Association of Hypertrophic Cardiomyopathy with Complete Atrioventricular Canal Defect and Down Syndrome. by Eidem BW, Jones C, Cetta F.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101082
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Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1 /Hey2. by Sakata Y, Kamei CN, Nakagami H, Bronson R, Liao JK, Chin MT.; 2002 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138588
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 cardiomyopathy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “cardiomyopathy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for cardiomyopathy (hyperlinks lead to article summaries): 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A case of dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Author(s): Olgun H, Ceviz N, Ozkan B. Source: Turk J Pediatr. 2003 April-June; 45(2): 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921304&dopt=Abstract
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A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy. Author(s): Taylor RW, Giordano C, Davidson MM, d'Amati G, Bain H, Hayes CM, Leonard H, Barron MJ, Casali C, Santorelli FM, Hirano M, Lightowlers RN, DiMauro S, Turnbull DM. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1786-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767666&dopt=Abstract
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A new method using pulmonary gas-exchange kinetics to evaluate efficacy of betablocking agents in patients with dilated cardiomyopathy. Author(s): Taniguchi Y, Ueshima K, Chiba I, Segawa I, Kobayashi N, Saito M, Hiramori K. Source: Chest. 2003 September; 124(3): 954-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970023&dopt=Abstract
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A noninvasive means of detecting preclinical cardiomyopathy in Duchenne muscular dystrophy? Author(s): Towbin JA. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 317-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875770&dopt=Abstract
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A reversible form of cardiomyopathy. Author(s): Kini SM, Pednekar SJ, Nabar ST, Varthakavi P. Source: Journal of Postgraduate Medicine. 2003 January-March; 49(1): 85-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865580&dopt=Abstract
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Absolute quantitation of myocardial blood flow after nitroglycerin and ischemic cardiomyopathy with a low ejection fraction. Author(s): Bianco JA. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 November; 44(11): 1872; Author Reply 1872-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602873&dopt=Abstract
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Accuracy of European diagnostic criteria for familial hypertrophic cardiomyopathy in a genotyped population. Author(s): Charron P, Forissier JF, Amara ME, Dubourg O, Desnos M, Bouhour JB, Isnard R, Hagege A, Benaiche A, Richard P, Schwartz K, Komajda M. Source: International Journal of Cardiology. 2003 July; 90(1): 33-8; Discussion 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821216&dopt=Abstract
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Acromegaly with multiple cardiovascular complications--cardiomyopathy, chordae rupture of mitral valve, myocardial infarction and sick sinus syndrome. Author(s): Yamamoto T, Nakamura H, Ogawa T, Saga T, Ishikawa K. Source: Intern Med. 2003 August; 42(8): 700-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924495&dopt=Abstract
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Adverse prognosis of patients with hypertrophic cardiomyopathy who have epicardial coronary artery disease. Author(s): Sorajja P, Ommen SR, Nishimura RA, Gersh BJ, Berger PB, Tajik AJ. Source: Circulation. 2003 November 11; 108(19): 2342-8. Epub 2003 October 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581405&dopt=Abstract
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American College of Cardiology/European Society of Cardiology clinical expert consensus document on hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines. Author(s): Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH 3rd, Spirito P, Ten Cate FJ, Wigle ED, Vogel RA, Abrams J, Bates ER, Brodie BR, Danias PG, Gregoratos G, Hlatky MA, Hochman JS, Kaul S, Lichtenberg RC, Lindner JR, O'rourke RA, Pohost GM, Schofield RS, Tracy CM, Winters WL Jr, Klein WW, Priori SG, Alonso-Garcia A, Blomstrom-Lundqvist C, De Backer G, Deckers J, Flather M, Hradec J, Oto A, Parkhomenko A, Silber S, Torbicki A; Task Force on Clinical Expert Consensus Documents. American College of Cardiology; Committee for Practice Guidelines. European Society of Cardiology. Source: Journal of the American College of Cardiology. 2003 November 5; 42(9): 1687713. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607462&dopt=Abstract
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Amiodarone versus implantable cardioverter-defibrillator:randomized trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia--AMIOVIRT. Author(s): Strickberger SA, Hummel JD, Bartlett TG, Frumin HI, Schuger CD, Beau SL, Bitar C, Morady F; AMIOVIRT Investigators. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1707-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767651&dopt=Abstract
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An autopsy study of hypertrophic cardiomyopathy. Author(s): Ahmad M, Afzal S, Malik IA, Mushtaq S, Mubarik A. Source: J Pak Med Assoc. 2003 October; 53(10): 459-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14696885&dopt=Abstract
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Antiphospholipid syndrome presenting as dilated cardiomyopathy in an 11-year-old boy. Author(s): Al-Kiyumi WA, Venugopalan P. Source: Acta Cardiol. 2003 August; 58(4): 359-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948043&dopt=Abstract
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Apical hypertrophic cardiomyopathy: diagnosis with contrast-enhanced echocardiography--a case report. Author(s): Acarturk E, Bozkurt A, Donmez Y. Source: Angiology. 2003 May-June; 54(3): 373-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785033&dopt=Abstract
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Are anti-Chlamydia pneumoniae antibodies prognosis indicators for peripartum cardiomyopathy? Author(s): Cenac A, Djibo A, Chaigneau C, Velmans N, Orfila J. Source: Journal of Cardiovascular Risk. 2003 June; 10(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775952&dopt=Abstract
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Are imidazolic drugs effective in the treatment of chronic Chagas cardiomyopathy? Author(s): Vallejo M, Reyes PA. Source: Salud Publica De Mexico. 2003 July-August; 45(4): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974040&dopt=Abstract
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Area ablation of ventricular tachycardia in a patient with arrhythmogenic right ventricular cardiomyopathy. Author(s): de Groot NM, Schalij MJ, van der Wall EE. Source: Heart (British Cardiac Society). 2003 July; 89(7): 703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807832&dopt=Abstract
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Arrhythmogenic right ventricular cardiomyopathy: time for a new look. Author(s): Ferrari VA, Scott CH. Source: Journal of Cardiovascular Electrophysiology. 2003 May; 14(5): 483-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776864&dopt=Abstract
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Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C): a multidisciplinary study: design and protocol. Author(s): Marcus F, Towbin JA, Zareba W, Moss A, Calkins H, Brown M, Gear K; ARVD/C Investigators. Source: Circulation. 2003 June 17; 107(23): 2975-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814984&dopt=Abstract
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Ascertainment strategies and genotype:phenotype correlations in hypertrophic cardiomyopathy. Author(s): Blair E, Redwood C, Watkins H. Source: Circulation. 2003 July 29; 108(4): E24-5; Author Reply E24-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885737&dopt=Abstract
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Assessing risk in hypertrophic cardiomyopathy. Author(s): Cannon RO 3rd. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1016-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968084&dopt=Abstract
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Assessment of regional systolic and diastolic dysfunction in familial hypertrophic cardiomyopathy using MR tagging. Author(s): Ennis DB, Epstein FH, Kellman P, Fananapazir L, McVeigh ER, Arai AE. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 2003 September; 50(3): 638-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939774&dopt=Abstract
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Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin myocardial SPECT--comparison with acute coronary syndrome. Author(s): Ito K, Sugihara H, Katoh S, Azuma A, Nakagawa M. Source: Ann Nucl Med. 2003 April; 17(2): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790360&dopt=Abstract
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Association of cardiomyopathy caused by autonomic nervous system impairment with the Miller Fisher syndrome. Author(s): Oomura M, Yamawaki T, Oe H, Moriwaki H, Miyashita K, Naritomi H, Yasumura Y. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 May; 74(5): 689-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700327&dopt=Abstract
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Association of lipoproteins with cytokines and cytokine receptors in heart failure patients. Differences between ischaemic versus idiopathic cardiomyopathy. Author(s): Conraads VM, Bosmans JM, Schuerwegh AJ, De Clerck LS, Bridts CH, Wuyts FL, Stevens WJ, Vrints CJ. Source: European Heart Journal. 2003 December; 24(24): 2221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14659774&dopt=Abstract
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Atrophic degeneration and loss of myocytes of residual left ventricular myocardium after Dor operation for ischemic cardiomyopathy associated with left ventricular remodeling. Author(s): Kokaji K, Okamoto M, Hotoda K. Source: Jpn J Thorac Cardiovasc Surg. 2003 November; 51(11): 634-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650598&dopt=Abstract
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Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Author(s): Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, Ishida M, Hiai H, Matsumori A, Minato N, Honjo T. Source: Nature Medicine. 2003 December; 9(12): 1477-83. Epub 2003 November 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14595408&dopt=Abstract
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Autopsy findings in siblings with hypertrophic cardiomyopathy caused by Arg92Trp mutation in the cardiac troponin T gene showing dilated cardiomyopathy-like features. Author(s): Shimizu M, Ino H, Yamaguchi M, Terai H, Uchiyama K, Inoue M, Ikeda M, Kawashima A, Mabuchi H. Source: Clin Cardiol. 2003 November; 26(11): 536-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640471&dopt=Abstract
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Batista operation with aortic valve replacement for valvular cardiomyopathy. Author(s): Harada H, Honma Y, Hachiro Y, Baba T, Abe T. Source: Ann Thorac Cardiovasc Surg. 2003 April; 9(2): 138-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732094&dopt=Abstract
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Biomolecular interactions between human recombinant beta-MyHC and cMyBP-Cs implicated in familial hypertrophic cardiomyopathy. Author(s): Flavigny J, Robert P, Camelin JC, Schwartz K, Carrier L, Berrebi-Bertrand I. Source: Cardiovascular Research. 2003 November 1; 60(2): 388-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14613868&dopt=Abstract
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Blunted increase in plasma adenosine levels following dipyridamole stress in dilated cardiomyopathy patients. Author(s): Laghi-Pasini F, Guideri F, Petersen C, Lazzerini PE, Sicari R, Capecchi PL, Picano E. Source: Journal of Internal Medicine. 2003 December; 254(6): 591-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14641800&dopt=Abstract
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Brain natriuretic peptide as a predictor of cardiomyopathy in Chagas' disease. Author(s): Walther T, Heringer-Walther S, Wessel N, Schultheiss HP, Moreira Mda C. Source: Lancet. 2003 May 3; 361(9368): 1567. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737906&dopt=Abstract
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Cardiology patient page. Hypertrophic cardiomyopathy: a patient perspective. Author(s): Nishimura RA, Ommen SR, Tajik AJ. Source: Circulation. 2003 November 11; 108(19): E133-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609998&dopt=Abstract
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Cardiomyocyte apoptosis in hypertensive cardiomyopathy. Author(s): Gonzalez A, Fortuno MA, Querejeta R, Ravassa S, Lopez B, Lopez N, Diez J. Source: Cardiovascular Research. 2003 September 1; 59(3): 549-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499856&dopt=Abstract
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Cardiomyopathy in a murine model of AIDS: evidence of reactive nitrogen species and corroboration in human HIV/AIDS cardiac tissues. Author(s): Chaves AA, Mihm MJ, Schanbacher BL, Basuray A, Liu C, Ayers LW, Bauer JA. Source: Cardiovascular Research. 2003 October 15; 60(1): 108-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522412&dopt=Abstract
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Cardiomyopathy in muscular dystrophies. Author(s): Muntoni F. Source: Current Opinion in Neurology. 2003 October; 16(5): 577-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501841&dopt=Abstract
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Changes in cardiac sympathetic nerve innervation and activity in pathophysiologic transition from typical to end-stage hypertrophic cardiomyopathy. Author(s): Terai H, Shimizu M, Ino H, Yamaguchi M, Uchiyama K, Oe K, Nakajima K, Taki J, Kawano M, Mabuchi H. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 October; 44(10): 1612-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530475&dopt=Abstract
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Circumstances of death and gross and microscopic observations in a series of 200 cases of sudden death associated with arrhythmogenic right ventricular cardiomyopathy and/or dysplasia. Author(s): Tabib A, Loire R, Chalabreysse L, Meyronnet D, Miras A, Malicier D, Thivolet F, Chevalier P, Bouvagnet P. Source: Circulation. 2003 December 16; 108(24): 3000-5. Epub 2003 Dec 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662701&dopt=Abstract
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Cirrhotic cardiomyopathy: does it contribute to chronic fatigue and decreased healthrelated quality of life in cirrhosis? Author(s): Girgrah N, Reid G, MacKenzie S, Wong F. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 September; 17(9): 545-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532928&dopt=Abstract
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Clinical and genetic characteristics of alpha cardiac actin gene mutations in hypertrophic cardiomyopathy. Author(s): Mogensen J, Perrot A, Andersen PS, Havndrup O, Klausen IC, Christiansen M, Bross P, Egeblad H, Bundgaard H, Osterziel KJ, Haltern G, Lapp H, Reinecke P, Gregersen N, Borglum AD. Source: Journal of Medical Genetics. 2004 January; 41(1): E10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14729850&dopt=Abstract
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Clinical characteristics of and long-term outcome in Chinese patients with hypertrophic cardiomyopathy. Author(s): Ho HH, Lee KL, Lau CP, Tse HF. Source: The American Journal of Medicine. 2004 January 1; 116(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14706661&dopt=Abstract
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Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Author(s): Pignatelli RH, McMahon CJ, Dreyer WJ, Denfield SW, Price J, Belmont JW, Craigen WJ, Wu J, El Said H, Bezold LI, Clunie S, Fernbach S, Bowles NE, Towbin JA. Source: Circulation. 2003 November 25; 108(21): 2672-8. Epub 2003 Nov 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623814&dopt=Abstract
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Coexistence of familial hypertrophic cardiomyopathy and vasospastic angina pectoris in two brothers. Author(s): Suzuki N, Seto S, Koide Y, Sato O, Hirano H, Kawano H, Yano K. Source: Japanese Heart Journal. 2003 September; 44(5): 775-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587659&dopt=Abstract
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Combined cox maze procedure, septal myectomy, and mitral valve replacement for severe hypertrophic obstructive cardiomyopathy complicated by chronic atrial fibrillation. Author(s): Matsui Y, Fukada Y, Imai T, Naito Y, Sasaki S. Source: Ann Thorac Cardiovasc Surg. 2003 October; 9(5): 323-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672530&dopt=Abstract
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Comparison of effectiveness of implantable cardioverter defibrillator in patients with idiopathic dilated cardiomyopathy versus those with proved coronary heart disease. Author(s): Cuesta A, Mont L, Rogel U, Valentino M, Matas M, Brugada J. Source: The American Journal of Cardiology. 2003 November 15; 92(10): 1227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609607&dopt=Abstract
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Comparison of prevalence of apical hypertrophic cardiomyopathy in Japan and the United States. Author(s): Kitaoka H, Doi Y, Casey SA, Hitomi N, Furuno T, Maron BJ. Source: The American Journal of Cardiology. 2003 November 15; 92(10): 1183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609593&dopt=Abstract
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Conditional cardiac overexpression of endothelin-1 induces inflammation and dilated cardiomyopathy in mice. Author(s): Yang LL, Gros R, Kabir MG, Sadi A, Gotlieb AI, Husain M, Stewart DJ. Source: Circulation. 2004 January 20; 109(2): 255-61. Epub 2004 Jan 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14718401&dopt=Abstract
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Conduction system abnormalities in patients with obstructive hypertrophic cardiomyopathy following septal reduction interventions. Author(s): Qin JX, Shiota T, Lever HM, Asher CR, Popovic ZB, Greenberg NL, Agler DA, Drinko JK, Smedira NG, Tuzcu EM, Lytle BW, Thomas JD. Source: The American Journal of Cardiology. 2004 January 15; 93(2): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715342&dopt=Abstract
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Contrast echocardiography in segmental analysis and intraventricular gradient quantification in hypertrophic cardiomyopathy. Author(s): Candido A, Coucelo J, Galvao J, Azevedo V, Soares L, Anao AO, Bruno MJ, Arroja I, Fernandes J, Azevedo J, Joao I, Nunes JS, Aleixo A. Source: Rev Port Cardiol. 2003 June; 22(6): 789-98. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526696&dopt=Abstract
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Coronary microvascular dysfunction and prognosis in hypertrophic cardiomyopathy. Author(s): Cecchi F, Olivotto I, Gistri R, Lorenzoni R, Chiriatti G, Camici PG. Source: The New England Journal of Medicine. 2003 September 11; 349(11): 1027-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968086&dopt=Abstract
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Covered stent septal ablation for hypertrophic obstruction cardiomyopathy. Author(s): Anzuini A, Uretsky BF. Source: Circulation. 2004 January 20; 109(2): E6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14734509&dopt=Abstract
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Crystal methamphetamine-associated cardiomyopathy: tip of the iceberg? Author(s): Wijetunga M, Seto T, Lindsay J, Schatz I. Source: Journal of Toxicology. Clinical Toxicology. 2003; 41(7): 981-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14705845&dopt=Abstract
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Delayed dilated cardiomyopathy for major burn injuries. Author(s): Chen TJ, Shen BH, Yeh FL, Lin JT, Ma H, Huang CH, Fang RH. Source: Burns : Journal of the International Society for Burn Injuries. 2003 June; 29(4): 343-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781611&dopt=Abstract
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Detection of patients with hypertrophic cardiomyopathy at risk for paroxysmal atrial fibrillation during sinus rhythm by P-wave dispersion. Author(s): Kose S, Aytemir K, Sade E, Can I, Ozer N, Amasyali B, Aksoyek S, Ovunc K, Ozmen F, Atalar E, Isik E, Kes S, Demirtas E, Oto A. Source: Clin Cardiol. 2003 September; 26(9): 431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14524601&dopt=Abstract
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Diabetic cardiomyopathy. the importance of being earliest. Author(s): Picano E. Source: Journal of the American College of Cardiology. 2003 August 6; 42(3): 454-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906971&dopt=Abstract
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Diagnostic usefulness of carotid pulse tracing in patients with hypertrophic obstructive cardiomyopathy due to midventricular obstruction: a comparison with idiopathic hypertrophic subaortic stenosis. Author(s): Hamada M, Shigematsu Y, Ohshima K, Suzuki J, Ogimoto A, Ohtsuka T, Hara Y. Source: Chest. 2003 October; 124(4): 1275-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555556&dopt=Abstract
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Diastolic paradoxic jet flow in patients with hypertrophic cardiomyopathy: report of two patients with different morphologic aspects. Author(s): Mangano S, Carerj S, Pugliatti P, Cavallaro L, La Rosa A, Grassi R. Source: Echocardiography (Mount Kisco, N.Y.). 2003 April; 20(3): 279-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848666&dopt=Abstract
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Diastolic ventricular dysfunction as a marker for hypertrophic cardiomyopathy in a family with a novel alpha-tropomyosin mutation. Author(s): Earing MG, Ackerman MJ, O'Leary PW. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 June; 16(6): 698-702. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778034&dopt=Abstract
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Different functional properties of troponin T mutants that cause dilated cardiomyopathy. Author(s): Venkatraman G, Harada K, Gomes AV, Kerrick WG, Potter JD. Source: The Journal of Biological Chemistry. 2003 October 24; 278(43): 41670-6. Epub 2003 August 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923187&dopt=Abstract
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Different presentation of hypertrophic cardiomyopathy in monozygotic twins. Author(s): Palka P, Lange A, Burstow DJ. Source: Heart (British Cardiac Society). 2003 July; 89(7): 751. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807848&dopt=Abstract
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Differentiation of ischemic from nonischemic cardiomyopathy during dobutamine stress by left ventricular long-axis function: additional effect of left bundle-branch block. Author(s): Duncan AM, Francis DP, Gibson DG, Henein MY. Source: Circulation. 2003 September 9; 108(10): 1214-20. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939221&dopt=Abstract
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Difficult cases in heart failure. Percutaneous transluminal septal myocardial ablation in the management of hypertrophic obstructive cardiomyopathy. Author(s): Feghali G, Alaeddini J, Ramee S, Ventura HO. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 November-December; 9(6): 343-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14688508&dopt=Abstract
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Dilated cardiomyopathy after electrical injury: report of two cases. Author(s): Buono LM, DePace NL, Elbaum DM. Source: J Am Osteopath Assoc. 2003 May; 103(5): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776766&dopt=Abstract
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Dilated cardiomyopathy due to endocrine dysfunction. Author(s): Brito D, Pedro M, Bordalo A, Orgando AL, Aguiar A, Gouveia R, Martins AP, Vagueiro MC, Madeira H. Source: Rev Port Cardiol. 2003 March; 22(3): 377-87. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847879&dopt=Abstract
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Dilated cardiomyopathy in an adult human immunodeficiency virus type 1-positive patient treated with a zidovudine-containing antiretroviral regimen. Author(s): Tanuma J, Ishizaki A, Gatanaga H, Kikuchi Y, Kimura S, Hiroe M, Oka S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 October 1; 37(7): E109-11. Epub 2003 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130421&dopt=Abstract
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Dilated cardiomyopathy in Indian children. Author(s): Kothari SS, Dhopeshwarkar RA, Saxena A, Juneja R. Source: Indian Heart J. 2003 March-April; 55(2): 147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921329&dopt=Abstract
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Dilated cardiomyopathy: a disease of the intercalated disc? Author(s): Perriard JC, Hirschy A, Ehler E. Source: Trends in Cardiovascular Medicine. 2003 January; 13(1): 30-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554098&dopt=Abstract
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Dilated cardiomyopathy: learning to live with yourself. Author(s): MacLellan WR, Lusis AJ. Source: Nature Medicine. 2003 December; 9(12): 1455-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14647516&dopt=Abstract
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Do some genetic mutations predict the development of dilated cardiomyopathy in patients with Becker's muscular dystrophy? Author(s): Ozdemir O, Arda K, Soylu M, Kutuk E. Source: Angiology. 2003 May-June; 54(3): 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785035&dopt=Abstract
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Doppler estimation of filling pressures in a patient with hypertrophic cardiomyopathy. Author(s): Paelinck BP, Vrints CJ, Gillebert TC. Source: Echocardiography (Mount Kisco, N.Y.). 2003 February; 20(2): 163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848681&dopt=Abstract
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Dual-chamber pacing in hypertrophic obstructive cardiomyopathy with biventricular outflow tract obstruction and severe drug-refractory symptoms in a 9-year-old girl. Author(s): Ohtani K, Satoh A, Eto S, Satoh T, Ichinose K, Satoh S, Takahashi T, Koda M, Kinjo M, Yonesaka S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 December; 45(6): 743-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14651555&dopt=Abstract
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Dysregulation of endogenous carbon monoxide and nitric oxide production in patients with advanced ischemic or nonischemic cardiomyopathy. Author(s): Seshadri N, Dweik RA, Laskowski D, Pothier C, Rodriguez L, Young JB, Migrino RQ. Source: The American Journal of Cardiology. 2003 October 1; 92(7): 820-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516883&dopt=Abstract
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Early versus delayed revascularization in patients with ischemic cardiomyopathy and substantial viability: impact on outcome. Author(s): Bax JJ, Schinkel AF, Boersma E, Rizzello V, Elhendy A, Maat A, Roelandt JR, van der Wall EE, Poldermans D. Source: Circulation. 2003 September 9; 108 Suppl 1: Ii39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970206&dopt=Abstract
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Effect of nicorandil on left ventricular end-diastolic pressure during exercise in patients with hypertrophic cardiomyopathy. Author(s): Izawa H, Iwase M, Takeichi Y, Somura F, Nagata K, Nishizawa T, Noda A, Murohara T, Yokota M. Source: European Heart Journal. 2003 July; 24(14): 1340-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12871691&dopt=Abstract
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Effect of thoracic epidural blockade on plasma fibrinogen levels in patients with dilated cardiomyopathy. Author(s): Li Z, Liu F, Fu S, Qu R, Liu Z, Wu S. Source: Chinese Medical Journal. 2003 August; 116(8): 1191-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12935409&dopt=Abstract
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Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy. Author(s): Adamopoulos S, Parissis JT, Paraskevaidis I, Karatzas D, Livanis E, Georgiadis M, Karavolias G, Mitropoulos D, Degiannis D, Kremastinos DT. Source: European Heart Journal. 2003 December; 24(24): 2186-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14659770&dopt=Abstract
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Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Author(s): Zeng XH, Zeng XJ, Li YY. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860219&dopt=Abstract
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Efficacy of carvedilol treatment on cardiac function and cardiac sympathetic nerve activity in patients with dilated cardiomyopathy: comparison with metoprolol therapy. Author(s): Toyama T, Hoshizaki H, Seki R, Isobe N, Adachi H, Naito S, Oshima S, Taniguchi K. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 October; 44(10): 1604-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530474&dopt=Abstract
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Efficacy of endoventricular circular patch plasty: will this procedure improve the prognosis of patients with ischemic cardiomyopathy? Author(s): Kokaji K, Okamoto M, Hotoda K, Maehara T, Kumamaru H, Koizumi K. Source: Jpn J Thorac Cardiovasc Surg. 2004 January; 52(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14760984&dopt=Abstract
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Efficacy of implantable cardioverter defibrillator therapy for primary and secondary prevention of sudden cardiac death in hypertrophic cardiomyopathy. Author(s): Begley DA, Mohiddin SA, Tripodi D, Winkler JB, Fananapazir L. Source: Pacing and Clinical Electrophysiology : Pace. 2003 September; 26(9): 1887-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930505&dopt=Abstract
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Efficacy of modified endoventricular circular patch plasty in ischemic cardiomyopathy--innovative delimitation technique using integrated myocardial management. Author(s): Nakamura M, Okamoto F, Hatta E, Nakanishi K, Matano J, Sakai K. Source: Journal of Cardiac Surgery. 2003 July-August; 18 Suppl 2: S87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930275&dopt=Abstract
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Elevated plasma amylase levels in advanced chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy: correlation with circulating interleukin-6 activity. Author(s): Parissis JT, Adamopoulos SN, Venetsanou KF, Karas SM, Kremastinos DT. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2003 June; 23(6): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859859&dopt=Abstract
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Emerging insights into peripartum cardiomyopathy. Author(s): Fett JD, Carraway RD, Perry H, Dowell DL. Source: J Health Popul Nutr. 2003 March; 21(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751668&dopt=Abstract
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End-stage cardiomyopathy and secondary mitral insufficiency surgical alternative with prosthesis implant and left ventricular remodeling. Author(s): Buffolo E, de Paula IM, Aguiar LF, Branco JN. Source: Journal of Cardiac Surgery. 2003 May-June; 18(3): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809393&dopt=Abstract
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Enhanced washout of 99mTc-tetrofosmin in hypertrophic cardiomyopathy: quantitative comparisons with regional 123I-BMIPP uptake and wall thickness determined by MRI. Author(s): Thet-Thet-Lwin, Takeda T, Wu J, Fumikura Y, Iida K, Kawano S, Yamaguchi I, Itai Y. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2003 July; 30(7): 966-73. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756503&dopt=Abstract
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Evaluation of myocardial blood flow reserve in patients with chronic congestive heart failure due to idiopathic dilated cardiomyopathy. Author(s): Canetti M, Akhter MW, Lerman A, Karaalp IS, Zell JA, Singh H, Mehra A, Elkayam U. Source: The American Journal of Cardiology. 2003 November 15; 92(10): 1246-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609613&dopt=Abstract
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Evaluation of myocardial viability in chronic ischemic cardiomyopathy. Author(s): Bax JJ, van der Wall EE. Source: The International Journal of Cardiovascular Imaging. 2003 April; 19(2): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749394&dopt=Abstract
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Evaluation of the arrhythmogenecity of stress-induced “Takotsubo cardiomyopathy” from the time course of the 12-lead surface electrocardiogram. Author(s): Matsuoka K, Okubo S, Fujii E, Uchida F, Kasai A, Aoki T, Makino K, Omichi C, Fujimoto N, Ohta S, Sawai T, Nakano T. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 230-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860233&dopt=Abstract
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Evidence for anti-ischemic effect of dual-chamber pacing in patients with the obstructive form of hypertrophic cardiomyopathy. Author(s): Mohri M, Ichiki T, Kuga T, Takeshita A. Source: Japanese Heart Journal. 2003 July; 44(4): 587-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906041&dopt=Abstract
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Expanding the phenotype of LMNA mutations in dilated cardiomyopathy and functional consequences of these mutations. Author(s): Sebillon P, Bouchier C, Bidot LD, Bonne G, Ahamed K, Charron P, DrouinGarraud V, Millaire A, Desrumeaux G, Benaiche A, Charniot JC, Schwartz K, Villard E, Komajda M. Source: Journal of Medical Genetics. 2003 August; 40(8): 560-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920062&dopt=Abstract
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Expression profiling of human idiopathic dilated cardiomyopathy. Author(s): Grzeskowiak R, Witt H, Drungowski M, Thermann R, Hennig S, Perrot A, Osterziel KJ, Klingbiel D, Scheid S, Spang R, Lehrach H, Ruiz P. Source: Cardiovascular Research. 2003 August 1; 59(2): 400-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909323&dopt=Abstract
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Extreme hypertrophic cardiomyopathy. Author(s): Maron BJ, Casey SA, Almquist AK. Source: Heart (British Cardiac Society). 2004 January; 90(1): 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676234&dopt=Abstract
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Fabry disease: a mimic for obstructive hypertrophic cardiomyopathy? Author(s): Ommen SR, Nishimura RA, Edwards WD. Source: Heart (British Cardiac Society). 2003 August; 89(8): 929-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860876&dopt=Abstract
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Failure to raise blood pressure during exercise is a poor prognostic sign in patients with hypertrophic non-obstructive cardiomyopathy. Author(s): Isobe N, Toyama T, Taniguchi K, Oshima S, Kubota S, Suzuki T, Nagaoka H, Adachi H, Naito S, Hoshizaki H. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 March; 67(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604864&dopt=Abstract
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Familial dilated cardiomyopathy. Author(s): Martins E, Cardoso JS, Abreu-Lima C. Source: Rev Port Cardiol. 2002 December; 21(12): 1487-503. Review. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621922&dopt=Abstract
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Familial dilated cardiomyopathy: evidence for clinical and immunogenetic heterogeneity. Author(s): Bilinska ZT, Michalak E, Piatosa B, Grzybowski J, Skwarek M, Deptuch TW, Kusmierczyk-Droszcz B, Piotrowski W, Ruzyllo W. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 May; 9(5): Cr167-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761452&dopt=Abstract
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Familial hypertrophic cardiomyopathy-linked mutant troponin T causes stressinduced ventricular tachycardia and Ca2+-dependent action potential remodeling. Author(s): Knollmann BC, Kirchhof P, Sirenko SG, Degen H, Greene AE, Schober T, Mackow JC, Fabritz L, Potter JD, Morad M. Source: Circulation Research. 2003 March 7; 92(4): 428-36. Epub 2003 February 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600890&dopt=Abstract
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Familial restrictive cardiomyopathy with skeletal abnormalities. Author(s): Schwartz ML, Colan SD. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 636-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943897&dopt=Abstract
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Fibromuscular dysplasia of coronary arteries resulting in myocardial infarction associated with hypertrophic cardiomyopathy in Noonan's syndrome. Author(s): Ishikawa Y, Sekiguchi K, Akasaka Y, Ito K, Akishima Y, Zhang L, Itoh M, Ishihara M, Ishii T. Source: Human Pathology. 2003 March; 34(3): 282-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673564&dopt=Abstract
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First-pass MR imaging in the assessment of perfusion impairment in patients with hypertrophic cardiomyopathy and the Asp175Asn mutation of the alpha-tropomyosin gene. Author(s): Sipola P, Lauerma K, Husso-Saastamoinen M, Kuikka JT, Vanninen E, Laitinen T, Manninen H, Niemi P, Peuhkurinen K, Jaaskelainen P, Laakso M, Kuusisto J, Aronen HJ. Source: Radiology. 2003 January; 226(1): 129-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511681&dopt=Abstract
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Focal hypertrophic cardiomyopathy simulating a mass. Author(s): Gonzalez-Juanatey C, Testa-Fernandez A, Vidan J. Source: Clin Cardiol. 2003 November; 26(11): 539. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14640472&dopt=Abstract
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Frequency of development of idiopathic dilated cardiomyopathy among relatives of patients with idiopathic dilated cardiomyopathy. Author(s): Michels VV, Olson TM, Miller FA, Ballman KV, Rosales AG, Driscoll DJ. Source: The American Journal of Cardiology. 2003 June 1; 91(11): 1389-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767445&dopt=Abstract
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From malignant mutations to malignant domains: the continuing search for prognostic significance in the mutant genes causing hypertrophic cardiomyopathy. Author(s): Van Driest SL, Maron BJ, Ackerman MJ. Source: Heart (British Cardiac Society). 2004 January; 90(1): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676227&dopt=Abstract
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From sarcomeric mutations to heart disease: understanding familial hypertrophic cardiomyopathy. Author(s): Maass A, Konhilas JP, Stauffer BL, Leinwand LA. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 409-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858566&dopt=Abstract
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Functional consequences of mutations in the myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy. Author(s): Lowey S. Source: Trends in Cardiovascular Medicine. 2002 November; 12(8): 348-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536121&dopt=Abstract
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Gadolinium-enhanced magnetic resonance imaging in hypertrophic cardiomyopathy: in vivo imaging of the pathologic substrate for premature cardiac death? Author(s): Kim RJ, Judd RM. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1568-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742299&dopt=Abstract
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Ganglioneuroblastoma presenting as dilated cardiomyopathy. Author(s): Lee YH, Lee HD, Lee YA, Lee YS, Jung JA, Hwang GG, Jung GW, Kim DW, Roh MS. Source: Archives of Disease in Childhood. 2003 February; 88(2): 162-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538326&dopt=Abstract
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Genetics of arrhythmogenic right ventricular cardiomyopathy--status quo and future perspectives. Author(s): Paul M, Schulze-Bahr E, Breithardt G, Wichter T. Source: Zeitschrift Fur Kardiologie. 2003 February; 92(2): 128-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596074&dopt=Abstract
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Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study. Author(s): Kwan J, Shiota T, Agler DA, Popovic ZB, Qin JX, Gillinov MA, Stewart WJ, Cosgrove DM, McCarthy PM, Thomas JD; Real-time three-dimensional echocardiography study. Source: Circulation. 2003 March 4; 107(8): 1135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615791&dopt=Abstract
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Heart rate turbulence and clinical prognosis in hypertrophic cardiomyopathy and myocardial infarction. Author(s): Kawasaki T, Azuma A, Asada S, Hadase M, Kamitani T, Kawasaki S, Kuribayashi T, Sugihara H. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 July; 67(7): 601-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845183&dopt=Abstract
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Heart transplantation in chemotherapeutic dilated cardiomyopathy. Author(s): Grande AM, Rinaldi M, Sinelli S, D'Armini AM, Vigano M. Source: Transplantation Proceedings. 2003 June; 35(4): 1516-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826209&dopt=Abstract
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Hemodynamic improvement and removal of autoantibodies against beta1-adrenergic receptor by immunoadsorption therapy in dilated cardiomyopathy. Author(s): Mobini R, Staudt A, Felix SB, Baumann G, Wallukat G, Deinum J, Svensson H, Hjalmarson A, Fu M. Source: Journal of Autoimmunity. 2003 June; 20(4): 345-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791320&dopt=Abstract
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Hemodynamics during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia: a retrospective study. Author(s): Suzuki T, Shiga T, Wakaumi M, Matsuda N, Ishizuka N, Kasanuki H. Source: J Cardiol. 2003 April; 41(4): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728537&dopt=Abstract
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HLA-DRB1 gene polymorphism in patients with dilated cardiomyopathy. Author(s): Wang Q, Liao Y, Gong F, Mao H, Zhang J. Source: J Tongji Med Univ. 2000; 20(2): 141-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845730&dopt=Abstract
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Hypertension and heart failure sine heart failure. The ACC/AHA guidelines: a misadventure in the lexicography of cardiomyopathy and heart failure, particularly for the hypertensive. Author(s): Giles TD. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 280-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939569&dopt=Abstract
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Hypertrophic cardiomyopathy and diastolic dysfunction. Author(s): Shah PM. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 286-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875765&dopt=Abstract
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Hypertrophic cardiomyopathy and outflow tract obstruction. Author(s): Spevack DM. Source: The New England Journal of Medicine. 2003 May 1; 348(18): 1815-6; Author Reply 1815-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728916&dopt=Abstract
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Hypertrophic cardiomyopathy and outflow tract obstruction. Author(s): Iqbal K, Tramboo NA, Mohi-Ud-Din K. Source: The New England Journal of Medicine. 2003 May 1; 348(18): 1815-6; Author Reply 1815-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728915&dopt=Abstract
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Hypertrophic cardiomyopathy and outflow tract obstruction. Author(s): Monserrat L, Penas-Lado M, Castro-Beiras A. Source: The New England Journal of Medicine. 2003 May 1; 348(18): 1815-6; Author Reply 1815-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724493&dopt=Abstract
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Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy. Author(s): Crilley JG, Boehm EA, Blair E, Rajagopalan B, Blamire AM, Styles P, McKenna WJ, Ostman-Smith I, Clarke K, Watkins H. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1776-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767664&dopt=Abstract
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Hypertrophic cardiomyopathy: an important global disease. Author(s): Maron BJ. Source: The American Journal of Medicine. 2004 January 1; 116(1): 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14706671&dopt=Abstract
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Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Author(s): Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M; EUROGENE Heart Failure Project. Source: Circulation. 2003 May 6; 107(17): 2227-32. Epub 2003 April 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707239&dopt=Abstract
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Hypertrophic cardiomyopathy: low frequency of mutations in the beta-myosin heavy chain (MYH7) and cardiac troponin T (TNNT2) genes among Spanish patients. Author(s): Garcia-Castro M, Reguero JR, Batalla A, Diaz-Molina B, Gonzalez P, Alvarez V, Cortina A, Cubero GI, Coto E. Source: Clinical Chemistry. 2003 August; 49(8): 1279-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881443&dopt=Abstract
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Hypertrophic cardiomyopathy: two homozygous cases with “typical” hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy. Author(s): Nanni L, Pieroni M, Chimenti C, Simionati B, Zimbello R, Maseri A, Frustaci A, Lanfranchi G. Source: Biochemical and Biophysical Research Communications. 2003 September 19; 309(2): 391-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12951062&dopt=Abstract
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Hypertrophic cardiomyopathy: who plays and who sits. Author(s): Rizvi AA, Thompson PD. Source: Curr Sports Med Rep. 2002 April; 1(2): 93-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831717&dopt=Abstract
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Hypertrophic cardiomyopathy:a paradigm for myocardial energy depletion. Author(s): Ashrafian H, Redwood C, Blair E, Watkins H. Source: Trends in Genetics : Tig. 2003 May; 19(5): 263-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711218&dopt=Abstract
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Hypertrophic obstructive cardiomyopathy and septal ablation. Author(s): Steinbis S. Source: Critical Care Nurse. 2003 June; 23(3): 47-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830780&dopt=Abstract
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Hypertrophic obstructive cardiomyopathy: mechanism of obstruction and response to therapy. Author(s): Yoerger DM, Weyman AE. Source: Reviews in Cardiovascular Medicine. 2003 Fall; 4(4): 199-215. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14668688&dopt=Abstract
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Hypocalcemic rickets: an unusual cause of dilated cardiomyopathy. Author(s): Price DI, Stanford LC Jr, Braden DS, Ebeid MR, Smith JC. Source: Pediatric Cardiology. 2003 September-October; 24(5): 510-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627327&dopt=Abstract
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Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Author(s): Hayashi T, Arimura T, Ueda K, Shibata H, Hohda S, Takahashi M, Hori H, Koga Y, Oka N, Imaizumi T, Yasunami M, Kimura A. Source: Biochemical and Biophysical Research Communications. 2004 January 2; 313(1): 178-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14672715&dopt=Abstract
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Identification of the genotypes causing hypertrophic cardiomyopathy in northern Sweden. Author(s): Morner S, Richard P, Kazzam E, Hellman U, Hainque B, Schwartz K, Waldenstrom A. Source: Journal of Molecular and Cellular Cardiology. 2003 July; 35(7): 841-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818575&dopt=Abstract
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Idiopathic cardiomyopathy and recurrent wide QRS tachycardia. Author(s): Delacretaz E, Fuhrer J, Mohacsi P. Source: Pacing and Clinical Electrophysiology : Pace. 2003 June; 26(6): 1407-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822757&dopt=Abstract
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Images in cardiovascular medicine. Covered stent septal ablation for hypertrophic obstructive cardiomyopathy: initial success but ultimate failure resulting from collateral formation. Author(s): Fifer MA, Yoerger DM, Picard MH, Vlahakes GJ, Palacios IF. Source: Circulation. 2003 July 1; 107(25): 3248-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835408&dopt=Abstract
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Images in cardiovascular medicine. Epicardial real-time 3-dimensional echocardiography during septal myectomy for obstructive hypertrophic cardiomyopathy. Author(s): Nash PJ, Agler DA, Shin JH, Qin J, Smedira NG, Lever HM, Shiota T, Thomas JD. Source: Circulation. 2003 August 26; 108(8): E54-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939245&dopt=Abstract
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Images in cardiovascular medicine. Rapid progression of extreme septal hypertrophic cardiomyopathy. Author(s): Jefferies JL, Moreira W, Massumi A, Stainback RF. Source: Circulation. 2003 November 11; 108(19): E136. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609999&dopt=Abstract
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Impaired VE-cadherin/beta-catenin expression mediates endothelial cell degeneration in dilated cardiomyopathy. Author(s): Schafer R, Abraham D, Paulus P, Blumer R, Grimm M, Wojta J, Aharinejad S. Source: Circulation. 2003 September 30; 108(13): 1585-91. Epub 2003 Sep 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963640&dopt=Abstract
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Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Author(s): Corrado D, Leoni L, Link MS, Della Bella P, Gaita F, Curnis A, Salerno JU, Igidbashian D, Raviele A, Disertori M, Zanotto G, Verlato R, Vergara G, Delise P, Turrini P, Basso C, Naccarella F, Maddalena F, Estes NA 3rd, Buja G, Thiene G. Source: Circulation. 2003 December 23; 108(25): 3084-91. Epub 2003 November 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638546&dopt=Abstract
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Importance of mitral valve repair associated with left ventricular reconstruction for patients with ischemic cardiomyopathy: a real-time three-dimensional echocardiographic study. Author(s): Qin JX, Shiota T, McCarthy PM, Asher CR, Hail M, Agler DA, Popovic ZB, Greenberg NL, Smedira NG, Starling RC, Young JB, Thomas JD. Source: Circulation. 2003 September 9; 108 Suppl 1: Ii241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970240&dopt=Abstract
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Improved early outcome for end-stage dilated cardiomyopathy in children. Author(s): McMahon AM, van Doorn C, Burch M, Whitmore P, Neligan S, Rees P, Radley-Smith R, Goldman A, Brown K, Cohen G, Tsang V, Elliott M. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 December; 126(6): 1781-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14688687&dopt=Abstract
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Improvement in hypertrophic cardiomyopathy after significant weight loss: case report. Author(s): Uwaifo GI, Fallon EM, Calis KA, Drinkard B, McDuffie JR, Yanovski JA. Source: Southern Medical Journal. 2003 June; 96(6): 626-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938797&dopt=Abstract
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Improvement of peripheral endothelial dysfunction by acute vitamin C application: different effects in patients with coronary artery disease, ischemic, and dilated cardiomyopathy. Author(s): Erbs S, Gielen S, Linke A, Mobius-Winkler S, Adams V, Baither Y, Schuler G, Hambrecht R. Source: American Heart Journal. 2003 August; 146(2): 280-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891196&dopt=Abstract
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Improvement of ventricular arrhythmia by octreotide treatment in acromegalic cardiomyopathy. Author(s): Tachibana H, Yamaguchi H, Abe S, Sato T, Inoue S, Abe S, Yamaki M, Kubota I. Source: Japanese Heart Journal. 2003 November; 44(6): 1027-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14711197&dopt=Abstract
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Increased plasma levels of tumor necrosis factor-alpha in asymptomatic/”indeterminate” and Chagas disease cardiomyopathy patients. Author(s): Ferreira RC, Ianni BM, Abel LC, Buck P, Mady C, Kalil J, Cunha-Neto E. Source: Memorias Do Instituto Oswaldo Cruz. 2003 April; 98(3): 407-11. Epub 2003 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886425&dopt=Abstract
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Individual prediction of functional recovery after coronary revascularization in patients with ischemic cardiomyopathy: the scar-to-biphasic model. Author(s): Rizzello V, Schinkel AF, Bax JJ, Boersma E, Bountioukos M, Vourvouri EC, Krenning B, Agricola E, Roelandt JR, Poldermans D. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1406-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804724&dopt=Abstract
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Insulin resistance in dilated cardiomyopathy. Author(s): Shah A, Shannon RP. Source: Reviews in Cardiovascular Medicine. 2003; 4 Suppl 6: S50-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14668703&dopt=Abstract
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Is peripartum cardiomyopathy an organ-specific autoimmune disease? Author(s): Sundstrom JB, Fett JD, Carraway RD, Ansari AA. Source: Autoimmunity Reviews. 2002 February; 1(1-2): 73-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849062&dopt=Abstract
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Ischemia due to peripartum cardiomyopathy threatening loss of a leg. Author(s): Gagne PJ, Newman JB, Muhs BE. Source: Cardiology in the Young. 2003 April; 13(2): 209-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887083&dopt=Abstract
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Ischemic cardiomyopathy: value of different MRI techniques for prediction of functional recovery after revascularization. Author(s): Van Hoe L, Vanderheyden M. Source: Ajr. American Journal of Roentgenology. 2004 January; 182(1): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684520&dopt=Abstract
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Isolated left ventricular non-compaction: cardiomyopathy with homogeneous transmural and heterogeneous segmental perfusion. Author(s): Borges AC, Kivelitz D, Baumann G. Source: Heart (British Cardiac Society). 2003 August; 89(8): E21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860887&dopt=Abstract
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Late improvement in ventricular performance following internal cardioversion for persistent atrial fibrillation: an argument in support of concealed cardiomyopathy. Author(s): Boriani G, Biffi M, Rapezzi C, Ferlito M, Bronzetti G, Bacchi L, Zannoli R, Branzi A. Source: Pacing and Clinical Electrophysiology : Pace. 2003 May; 26(5): 1218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765450&dopt=Abstract
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Late-Onset visceral presentation with cardiomyopathy and without neurological symptoms of adult Sanfilippo A syndrome. Author(s): Van Hove JL, Wevers RA, Van Cleemput J, Moerman P, Sciot R, Matthijs G, Schollen E, de Jong JG, Carey WF, Muller V, Nicholls C, Perkins K, Hopwood JJ. Source: American Journal of Medical Genetics. 2003 May 1; 118A(4): 382-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687673&dopt=Abstract
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Left ventricular enlargement is common in relatives of patients with dilated cardiomyopathy. Author(s): Bilinska ZT, Michalak E, Kusmierczyk-Droszcz B, Rydlewska-Sadowska W, Grzybowski J, Kupsc W, Ruzyllo W. Source: Journal of Cardiac Failure. 1995 December; 1(5): 347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836709&dopt=Abstract
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Left ventricular restoration for ischemic cardiomyopathy--comparison of presence and absence of mitral valve procedure. Author(s): Isomura T, Suma H, Yamaguchi A, Kobashi T, Yuda A. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2003 April; 23(4): 614-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694786&dopt=Abstract
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Left ventricular systolic dysfunction and ischemic cardiomyopathy. Author(s): Henry LB. Source: Critical Care Nursing Quarterly. 2003 January-March; 26(1): 16-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669942&dopt=Abstract
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Left ventricular systolic dysfunction and nonischemic cardiomyopathy. Author(s): Tarolli KA. Source: Critical Care Nursing Quarterly. 2003 January-March; 26(1): 3-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669941&dopt=Abstract
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Left ventricular wall stress as a direct correlate of cardiomyocyte apoptosis in patients with severe dilated cardiomyopathy. Author(s): Di Napoli P, Taccardi AA, Grilli A, Felaco M, Balbone A, Angelucci D, Gallina S, Calafiore AM, De Caterina R, Barsotti A. Source: American Heart Journal. 2003 December; 146(6): 1105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14661007&dopt=Abstract
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Left ventriculoplasty for nonischemic dilated cardiomyopathy. Author(s): Horii T, Isomura T, Komeda M, Suma H. Source: Journal of Cardiac Surgery. 2003 March-April; 18(2): 121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757338&dopt=Abstract
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LGMD2E patients risk developing dilated cardiomyopathy. Author(s): Fanin M, Melacini P, Boito C, Pegoraro E, Angelini C. Source: Neuromuscular Disorders : Nmd. 2003 May; 13(4): 303-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868499&dopt=Abstract
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Limitation of cardiac output by total isovolumic time during pharmacologic stress in patients with dilated cardiomyopathy: activation-mediated effects of left bundle branch block and coronary artery disease. Author(s): Duncan AM, Francis DP, Henein MY, Gibson DG. Source: Journal of the American College of Cardiology. 2003 January 1; 41(1): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570954&dopt=Abstract
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Linkage analysis of five Chinese families with arrhythmogenic right ventricular cardiomyopathy using microsatellite genetic markers. Author(s): Huang J, Yang C, Ma L, Shan Q, Xu D, Hua Z, Cao K. Source: Chinese Medical Journal. 2003 November; 116(11): 1701-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14642141&dopt=Abstract
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Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. Author(s): Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, Seo T, Hu Y, Lutz EP, Merkel M, Bensadoun A, Homma S, Goldberg IJ. Source: The Journal of Clinical Investigation. 2003 February; 111(3): 419-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569168&dopt=Abstract
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Long-term glucose insulin potassium infusion improves systolic and diastolic function in patients with chronic ischemic cardiomyopathy. Author(s): Alan S, Ulgen MS, Dedeoglu I, Kaya H, Toprak N. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2003 July 26; 133(29-30): 419-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14562192&dopt=Abstract
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Long-term improvements in quality of life by biventricular pacing in patients with chronic heart failure: results from the Multisite Stimulation in Cardiomyopathy study (MUSTIC). Author(s): Linde C, Braunschweig F, Gadler F, Bailleul C, Daubert JC. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1090-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714152&dopt=Abstract
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Loss of lamin A/C expression revealed by immuno-electron microscopy in dilated cardiomyopathy with atrioventricular block caused by LMNA gene defects. Author(s): Verga L, Concardi M, Pilotto A, Bellini O, Pasotti M, Repetto A, Tavazzi L, Arbustini E. Source: Virchows Archiv : an International Journal of Pathology. 2003 November; 443(5): 664-71. Epub 2003 July 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898247&dopt=Abstract
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Mechanisms of the pathogenesis of troponin T-based familial hypertrophic cardiomyopathy. Author(s): Maass AH, Leinwand LA. Source: Trends in Cardiovascular Medicine. 2003 August; 13(6): 232-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922019&dopt=Abstract
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Microcephaly-cardiomyopathy syndrome: expansion of the phenotype. Author(s): Becker K, Yates R. Source: Journal of Medical Genetics. 2003 June; 40(6): E78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807977&dopt=Abstract
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Midaortic syndrome in the fetus and premature newborn: a new etiology of nonimmune hydrops fetalis and reversible fetal cardiomyopathy. Author(s): Zeltser I, Parness IA, Ko H, Holzman IR, Kamenir SA. Source: Pediatrics. 2003 June; 111(6 Pt 1): 1437-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777568&dopt=Abstract
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Mid-ventricular paradoxical dynamic obstruction in a right-sided secondary hypertrophic cardiomyopathy. Author(s): de Gregorio C, Micari A, Triboto F, Arrigo F, Coglitore S. Source: Ital Heart J. 2003 July; 4(7): 492-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558303&dopt=Abstract
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Mitral valve in ischemic versus idiopathic dilated cardiomyopathy. Author(s): Grossi EA, Sharony R, Colvin SB. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 September; 126(3): 922. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502200&dopt=Abstract
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Mitral valve repair in uremic congestive cardiomyopathy. Author(s): Chang JP, Kao CL. Source: The Annals of Thoracic Surgery. 2003 September; 76(3): 694-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963180&dopt=Abstract
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Modified septal myectomy and repair of mitral valve apparatus for the treatment of hypertrophic cardiomyopathy. Author(s): Paruchuru PK, Patel RL. Source: J Heart Valve Dis. 2003 July; 12(4): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918858&dopt=Abstract
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Multiple coronary artery-left ventricular microfistulae in a patient with apical hypertrophic cardiomyopathy: a demonstration by transthoracic color Doppler echocardiography. Author(s): Hong GR, Choi SH, Kang SM, Lee MH, Rim SJ, Jang YS, Chung NS. Source: Yonsei Medical Journal. 2003 August 30; 44(4): 710-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950129&dopt=Abstract
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Muscular dystrophies, dilated cardiomyopathy, lipodystrophy and neuropathy: the nuclear connection. Author(s): Maidment SL, Ellis JA. Source: Expert Reviews in Molecular Medicine [electronic Resource]. 2002 July 30; 2002: 1-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585157&dopt=Abstract
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Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. Author(s): Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA. Source: Journal of the American College of Cardiology. 2003 December 3; 42(11): 201427. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662268&dopt=Abstract
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Mutations of the beta myosin heavy chain gene in hypertrophic cardiomyopathy: critical functional sites determine prognosis. Author(s): Woo A, Rakowski H, Liew JC, Zhao MS, Liew CC, Parker TG, Zeller M, Wigle ED, Sole MJ. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975413&dopt=Abstract
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Myocardial bridging in adult patients with hypertrophic cardiomyopathy. Author(s): Sorajja P, Ommen SR, Nishimura RA, Gersh BJ, Tajik AJ, Holmes DR. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 889-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957438&dopt=Abstract
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Myocardial collagen turnover in hypertrophic cardiomyopathy. Author(s): Lombardi R, Betocchi S, Losi MA, Tocchetti CG, Aversa M, Miranda M, D'Alessandro G, Cacace A, Ciampi Q, Chiariello M. Source: Circulation. 2003 September 23; 108(12): 1455-60. Epub 2003 Sep 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952838&dopt=Abstract
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Myocardial infarction after percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: evaluation by contrast-enhanced magnetic resonance imaging. Author(s): van Dockum WG, ten Cate FJ, ten Berg JM, Beek AM, Twisk JW, Vos J, Hofman MB, Visser CA, van Rossum AC. Source: Journal of the American College of Cardiology. 2004 January 7; 43(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715178&dopt=Abstract
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Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy. Author(s): Stolen KQ, Kemppainen J, Kalliokoski KK, Karanko H, Toikka J, Janatuinen T, Raitakari OT, Airaksinen KE, Nuutila P, Knuuti J. Source: The American Journal of Cardiology. 2004 January 1; 93(1): 64-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14697468&dopt=Abstract
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Myocardial ultrasound tissue characterization in patients with hypertrophic cardiomyopathy: noninvasive evidence of electrical and textural substrate for ventricular arrhythmias. Author(s): Limongelli G, Pacileo G, Cerrato F, Verrengia M, Di Simone A, Severino S, Sarubbi B, Calabro R. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 August; 16(8): 803-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878988&dopt=Abstract
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Myocardial velocity gradient as a noninvasively determined index of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy. Author(s): Kato T, Noda A, Izawa H, Nishizawa T, Somura F, Yamada A, Nagata K, Iwase M, Nakao A, Yokota M. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 278-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875764&dopt=Abstract
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Myocarditis and dilated cardiomyopathy: an inflammatory link. Author(s): Mason JW. Source: Cardiovascular Research. 2003 October 15; 60(1): 5-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522402&dopt=Abstract
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Myocarditis and inflammatory cardiomyopathy: microbiological and molecular biological aspects. Author(s): Calabrese F, Thiene G. Source: Cardiovascular Research. 2003 October 15; 60(1): 11-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522403&dopt=Abstract
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Myopathy with tubular aggregates and hypertrophic cardiomyopathy in a patient with type IIA von Willebrand disease. Author(s): Mares M, Sartori MT, Casonato A, Melacini P, Angelini C, Girolami A. Source: Haematologia. 1996; 27(4): 201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14651221&dopt=Abstract
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Natural history of dilated cardiomyopathy due to lamin A/C gene mutations. Author(s): Taylor MR, Fain PR, Sinagra G, Robinson ML, Robertson AD, Carniel E, Di Lenarda A, Bohlmeyer TJ, Ferguson DA, Brodsky GL, Boucek MM, Lascor J, Moss AC, Li WL, Stetler GL, Muntoni F, Bristow MR, Mestroni L; Familial Dilated Cardiomyopathy Registry Research Group. Source: Journal of the American College of Cardiology. 2003 March 5; 41(5): 771-80. Erratum In: J Am Coll Cardiol. 2003 August 6; 42(3): 590. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628721&dopt=Abstract
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NCAM(CD56) and RUNX1(AML1) are up-regulated in human ischemic cardiomyopathy and a rat model of chronic cardiac ischemia. Author(s): Gattenlohner S, Waller C, Ertl G, Bultmann BD, Muller-Hermelink HK, Marx A. Source: American Journal of Pathology. 2003 September; 163(3): 1081-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937148&dopt=Abstract
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Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine. Author(s): Wijeysundera HC, Hansen MS, Stanton E, Cropp AS, Hall C, Dhalla NS, Ghali J, Rouleau JL; PRAISE II Investigators. Source: American Heart Journal. 2003 August; 146(2): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891198&dopt=Abstract
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New phenotype of familial dilated cardiomyopathy and conduction disorders. Author(s): Oropeza ES, Cadena CN. Source: American Heart Journal. 2003 February; 145(2): 317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595850&dopt=Abstract
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Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Author(s): Grimm W, Christ M, Bach J, Muller HH, Maisch B. Source: Circulation. 2003 December 9; 108(23): 2883-91. Epub 2003 November 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14623812&dopt=Abstract
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Noninvasive identification of myocardial sympathetic and metabolic abnormalities in a patient with restrictive cardiomyopathy--in comparison with perfusion imaging. Author(s): Matsuo S, Nakae I, Takada M, Murata K, Nakamura Y. Source: Ann Nucl Med. 2002 December; 16(8): 569-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593423&dopt=Abstract
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Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: short-term results in 50 consecutive procedures. Author(s): Nielsen CD, Killip D, Spencer WH 3rd. Source: Clin Cardiol. 2003 June; 26(6): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839045&dopt=Abstract
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Non-sustained ventricular tachycardia in hypertrophic cardiomyopathy: an independent marker of sudden death risk in young patients. Author(s): Monserrat L, Elliott PM, Gimeno JR, Sharma S, Penas-Lado M, McKenna WJ. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 873-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957435&dopt=Abstract
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Non-transplant cardiac surgery for end-stage dilated cardiomyopathy in small children. Author(s): Hsu RB, Chen RJ, Wu MH, Wang JK, Wang SS, Chu SH. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 January; 22(1): 94-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531419&dopt=Abstract
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Normalization of left ventricular parameters following combined pimobendan and carvedilol treatment in a case of unclassified cardiomyopathy with longstanding refractory status. Author(s): Takeda N, Ohtaki E, Misu K, Asano R, Tobaru T, Nagayama M, Kitahara K, Umemura J, Sumiyoshi T, Hosoda S. Source: Intern Med. 2002 December; 41(12): 1147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521204&dopt=Abstract
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Nuclear speckle localisation of the small heat shock protein alpha B-crystallin and its inhibition by the R120G cardiomyopathy-linked mutation. Author(s): van den IJssel P, Wheelock R, Prescott A, Russell P, Quinlan RA. Source: Experimental Cell Research. 2003 July 15; 287(2): 249-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837281&dopt=Abstract
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Obstructive hypertrophic cardiomyopathy: echocardiography, pathophysiology, and the continuing evolution of surgery for obstruction. Author(s): Sherrid MV, Chaudhry FA, Swistel DG. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 620-32. Review. Erratum In: Ann Thorac Surg. 2003 May; 75(5): 1684. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607696&dopt=Abstract
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On predictors of sudden cardiac death in hypertrophic cardiomyopathy. Author(s): Marian AJ. Source: Journal of the American College of Cardiology. 2003 March 19; 41(6): 994-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651047&dopt=Abstract
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Original report. Late myocardial enhancement in hypertrophic cardiomyopathy with contrast-enhanced MR imaging. Author(s): Bogaert J, Goldstein M, Tannouri F, Golzarian J, Dymarkowski S. Source: Ajr. American Journal of Roentgenology. 2003 April; 180(4): 981-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646440&dopt=Abstract
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Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations. Author(s): Havndrup O, Bundgaard H, Andersen PS, Allan Larsen L, Vuust J, Kjeldsen K, Christiansen M. Source: Cardiovascular Research. 2003 February; 57(2): 347-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566107&dopt=Abstract
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Outcome of clinical versus genetic family screening in hypertrophic cardiomyopathy with focus on cardiac beta-myosin gene mutations: prediction of clinical status--is molecular genetics a new tool for the management of hypertrophic cardiomyopathy in clinical practice? Author(s): Hengstenberg C, Erdmann J, Charron P. Source: Cardiovascular Research. 2003 February; 57(2): 298-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566102&dopt=Abstract
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Partial reversion of left ventricle remodeling in cardiomyopathy patients by means of transthoracic microelectrostimulation. Author(s): Kharchenko EP, Khubulava GG, Pyr'ev VB, Klimenko MN. Source: Doklady Biological Sciences : Proceedings of the Academy of Sciences of the Ussr, Biological Sciences Sections / Translated from Russian. 2001 September-October; 380: 438-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918398&dopt=Abstract
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Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy. Author(s): Senaratne V, Sathanandan S, Ekanayake RA. Source: Ceylon Med J. 2003 September; 48(3): 92-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14735809&dopt=Abstract
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Perioperative management of lobectomy in a patient with hypertrophic obstructive cardiomyopathy treated with dual-chamber pacing. Author(s): Amagasa S, Oda S, Abe S, Shinozaki K, Miura Y, Takaoka S, Horikawa H. Source: Journal of Anesthesia. 2003; 17(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908688&dopt=Abstract
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Peripartum cardiomyopathy. Author(s): Rao S, Shenoy JV, Giles RW, Clark JD. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 September; 23(5): 567-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963526&dopt=Abstract
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Peripartum cardiomyopathy: a spoiled birthday party. Author(s): de Ceuninck M, Vermeulen J, Vrints C. Source: Acta Cardiol. 2003 August; 58(4): 367-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948045&dopt=Abstract
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Permanent form of junctional reciprocating tachycardia and tachycardia-induced cardiomyopathy treated by catheter ablation: a case report. Author(s): Semizel E, Ayabakan C, Ceviz N, Celiker A. Source: Turk J Pediatr. 2003 October-December; 45(4): 338-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14768801&dopt=Abstract
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Persistent abnormal left ventricular systolic torsion in dilated cardiomyopathy after partial left ventriculectomy. Author(s): Setser RM, Kasper JM, Lieber ML, Starling RC, McCarthy PM, White RD. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 July; 126(1): 48-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878938&dopt=Abstract
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Phaeochromocytoma presenting as dilated cardiomyopathy. Author(s): Attar MN, Moulik PK, Salem GD, Rose EL, Khaleeli AA. Source: Int J Clin Pract. 2003 July-August; 57(6): 547-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918898&dopt=Abstract
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Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes. Author(s): Poirier P, Bogaty P, Philippon F, Garneau C, Fortin C, Dumesnil JG. Source: Metabolism: Clinical and Experimental. 2003 August; 52(8): 1056-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898473&dopt=Abstract
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Pregnancy related complications in women with hypertrophic cardiomyopathy. Author(s): Thaman R, Varnava A, Hamid MS, Firoozi S, Sachdev B, Condon M, Gimeno JR, Murphy R, Elliott PM, McKenna WJ. Source: Heart (British Cardiac Society). 2003 July; 89(7): 752-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807849&dopt=Abstract
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Pregnancy-related mortality due to cardiomyopathy: United States, 1991-1997. Author(s): Whitehead SJ, Berg CJ, Chang J. Source: Obstetrics and Gynecology. 2003 December; 102(6): 1326-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14662222&dopt=Abstract
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Prevalence and clinical profile of troponin T mutations among patients with hypertrophic cardiomyopathy in tuscany. Author(s): Torricelli F, Girolami F, Olivotto I, Passerini I, Frusconi S, Vargiu D, Richard P, Cecchi F. Source: The American Journal of Cardiology. 2003 December 1; 92(11): 1358-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636924&dopt=Abstract
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Prevalence of hepatitis C virus infection among patients with hypertrophic cardiomyopathy. Author(s): Teragaki M, Nishiguchi S, Takeuchi K, Yoshiyama M, Akioka K, Yoshikawa J. Source: Heart and Vessels. 2003 September; 18(4): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520482&dopt=Abstract
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Prevalence of idiopathic hypertrophic cardiomyopathy in China: a population-based echocardiographic analysis of 8080 adults. Author(s): Zou Y, Song L, Wang Z, Ma A, Liu T, Gu H, Lu S, Wu P, Zhang dagger Y, Shen dagger L, Cai Y, Zhen double dagger Y, Liu Y, Hui R. Source: The American Journal of Medicine. 2004 January 1; 116(1): 14-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14706660&dopt=Abstract
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Prognostic significance of heart rate turbulence following ventricular premature beats in patients with idiopathic dilated cardiomyopathy. Author(s): Grimm W, Schmidt G, Maisch B, Sharkova J, Muller HH, Christ M. Source: Journal of Cardiovascular Electrophysiology. 2003 August; 14(8): 819-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890042&dopt=Abstract
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Prognostic significance of morphometric endomyocardial biopsy analysis in patients with idiopathic dilated cardiomyopathy. Author(s): Grimm W, Rudolph S, Christ M, Pankuweit S, Maisch B. Source: American Heart Journal. 2003 August; 146(2): 372-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891210&dopt=Abstract
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Prognostic significance of post-exercise blood pressure response in patients with dilated cardiomyopathy. Author(s): Kitaoka H, Hitomi N, Okawa M, Furuno T, Doi Y. Source: J Cardiol. 2003 October; 42(4): 165-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14598718&dopt=Abstract
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Prognostic usefulness of echocardiographic dobutamine in younger (14 to 25 years) and older (40 to 55 years) patients with idiopathic dilated cardiomyopathy. Author(s): Paraskevaidis IA, Adamopoulos S, Tsiapras D, Karatzas D, Kremastinos DT. Source: The American Journal of Cardiology. 2004 January 15; 93(2): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14715363&dopt=Abstract
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Progression of familial and non-familial dilated cardiomyopathy: long term follow up. Author(s): Michels VV, Driscoll DJ, Miller FA, Olson TM, Atkinson EJ, Olswold CL, Schaid DJ. Source: Heart (British Cardiac Society). 2003 July; 89(7): 757-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807850&dopt=Abstract
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Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy. Author(s): Nakae I, Mitsunami K, Omura T, Yabe T, Tsutamoto T, Matsuo S, Takahashi M, Morikawa S, Inubushi T, Nakamura Y, Kinoshita M, Horie M. Source: Journal of the American College of Cardiology. 2003 November 5; 42(9): 1587-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607443&dopt=Abstract
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QT dispersion and left ventricular morphology in patients with hypertrophic cardiomyopathy. Author(s): Sakata K, Shimizu M, Ino H, Yamaguchi M, Terai H, Hayashi K, Kiyama M, Hayashi T, Inoue M, Mabuchi H. Source: Heart (British Cardiac Society). 2003 August; 89(8): 882-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860864&dopt=Abstract
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Quantification of regional left ventricular function in Q wave and non-Q wave dysfunctional regions by tissue Doppler imaging in patients with ischaemic cardiomyopathy. Author(s): Bountioukos M, Schinkel AF, Bax JJ, Rizzello V, Rambaldi R, Vourvouri EC, Roelandt JR, Poldermans D. Source: Heart (British Cardiac Society). 2003 November; 89(11): 1322-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594890&dopt=Abstract
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Quantitative analysis of cytokine mRNA expression in hearts from patients with nonischemic dilated cardiomyopathy (DCM). Author(s): Ukimura A, Terasaki F, Fujioka S, Deguchi H, Kitaura Y, Isomura T, Suma H. Source: Journal of Cardiac Surgery. 2003 July-August; 18 Suppl 2: S101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930277&dopt=Abstract
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Radionuclide viability testing: should it affect treatment strategy in patients with cardiomyopathy and significant coronary artery disease? Author(s): Bourque JM, Velazquez EJ, Borges-Neto S, Shaw LK, Whellan DJ, O'Connor CM. Source: American Heart Journal. 2003 May; 145(5): 758-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766731&dopt=Abstract
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Relation between microvolt-level T-wave alternans and cardiac sympathetic nervous system abnormality using iodine-123 metaiodobenzylguanidine imaging in patients with idiopathic dilated cardiomyopathy. Author(s): Harada M, Shimizu A, Murata M, Ono K, Kubo M, Mitani R, Dairaku Y, Matsumoto T, Yamagata T, Seki K, Matsuzaki M. Source: The American Journal of Cardiology. 2003 October 15; 92(8): 998-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556884&dopt=Abstract
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Relation between oxidative stress, catecholamines, and impaired chronotropic response to exercise in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Author(s): Castro PF, Greig D, Perez O, Moraga F, Chiong M, Diaz-Araya G, Padilla I, Nazzal C, Jalil JE, Vukasovic JL, Moreno M, Corbalan R, Lavandero S. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860229&dopt=Abstract
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Relation between QT dispersion and myocardial viability in ischemic cardiomyopathy. Author(s): Schinkel AF, Bountioukos M, Poldermans D, Elhendy A, Valkema R, Vourvouri EC, Biagini E, Rizzello V, Kertai MD, Krenning B, Krenning EP, Roelandt JR, Bax JJ. Source: The American Journal of Cardiology. 2003 September 15; 92(6): 712-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972115&dopt=Abstract
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Relation of cardiac sympathetic innervation to proinflammatory cytokine levels in patients with heart failure secondary to idiopathic dilated cardiomyopathy. Author(s): Parthenakis FI, Patrianakos A, Prassopoulos V, Papadimitriou E, Nikitovic D, Karkavitsas NS, Vardas PE. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1190-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745101&dopt=Abstract
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Relation of left ventricular thickness to age and gender in hypertrophic cardiomyopathy. Author(s): Maron BJ, Casey SA, Hurrell DG, Aeppli DM. Source: The American Journal of Cardiology. 2003 May 15; 91(10): 1195-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745102&dopt=Abstract
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Relations among heart failure severity, left ventricular loading conditions, and repolarization length in advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Author(s): Boccalandro F, Velasco A, Thomas C, Richards B, Radovancevic B. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 544-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943874&dopt=Abstract
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Relationship between exercise-induced myocardial ischemia and reduced left ventricular distensibility in patients with nonobstructive hypertrophic cardiomyopathy. Author(s): Isobe S, Izawa H, Takeichi Y, Nonokawa M, Nanasato M, Ando A, Kato K, Ikeda M, Murohara T, Yokota M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 November; 44(11): 1717-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14602851&dopt=Abstract
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Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy. Author(s): Maron BJ, Carney KP, Lever HM, Lewis JF, Barac I, Casey SA, Sherrid MV. Source: Journal of the American College of Cardiology. 2003 March 19; 41(6): 974-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651044&dopt=Abstract
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Reliability of QRS duration and morphology on surface electrocardiogram to identify ventricular dyssynchrony in patients with idiopathic dilated cardiomyopathy. Author(s): Fauchier L, Marie O, Casset-Senon D, Babuty D, Cosnay P, Fauchier JP. Source: The American Journal of Cardiology. 2003 August 1; 92(3): 341-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888151&dopt=Abstract
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Restrictive cardiomyopathy in familial amyloidosis TTR-Arg-50. Author(s): Boltwood CM Jr. Source: Circulation. 2003 September 9; 108(10): E71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966927&dopt=Abstract
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Restrictive cardiomyopathy in familial amyloidosis TTR-Arg-50. Author(s): Conraads V. Source: Circulation. 2003 September 9; 108(10): E71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963686&dopt=Abstract
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Restrictive cardiomyopathy in systemic amyloidosis. Author(s): Wald DS, Gray HH. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 May; 96(5): 380-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702790&dopt=Abstract
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Reversal of atrial mechanical dysfunction after cardioversion of atrial fibrillation: implications for the mechanisms of tachycardia-mediated atrial cardiomyopathy. Author(s): Sanders P, Morton JB, Kistler PM, Vohra JK, Kalman JM, Sparks PB. Source: Circulation. 2003 October 21; 108(16): 1976-84. Epub 2003 Oct 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557372&dopt=Abstract
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Reverse redistribution of Tc-99m tetrofosmin in a patient with “takotsubo” cardiomyopathy. Author(s): Hadase M, Kawasaki T, Asada S, Kamitani T, Kawasaki S, Sugihara H. Source: Clinical Nuclear Medicine. 2003 September; 28(9): 757-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972999&dopt=Abstract
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Reversible ventricular dysfunction (takotsubo cardiomyopathy) following polymorphic ventricular tachycardia. Author(s): Akashi YJ, Nakazawa K, Kida K, Ryu S, Takagi A, Kishi R, Kunishima T, Sakakibara M, Miyake F. Source: The Canadian Journal of Cardiology. 2003 March 31; 19(4): 449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704494&dopt=Abstract
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Right ventricular exclusion surgery for arrhythmogenic right ventricular dysplasia with cardiomyopathy. Author(s): Motta P, Mossad E, Savage R. Source: Anesthesia and Analgesia. 2003 June; 96(6): 1598-602, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760981&dopt=Abstract
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Right ventricular tachycardia-arrhythmogenic right ventricular cardiomyopathy or idiopathic? Author(s): Kottkamp H, Hindricks G. Source: European Heart Journal. 2003 May; 24(9): 787-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727145&dopt=Abstract
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Risk progression to chronic Chagas cardiomyopathy: influence of male sex and of parasitaemia detected by polymerase chain reaction. Author(s): Basquiera AL, Sembaj A, Aguerri AM, Omelianiuk M, Guzman S, Moreno Barral J, Caeiro TF, Madoery RJ, Salomone OA. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1186-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975414&dopt=Abstract
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Risk stratification in hypertrophic cardiomyopathy: fact or fiction? Author(s): Hess OM. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 880-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957436&dopt=Abstract
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Say no to primary prophylaxis with implantable cardioverter-defibrillators in asymptomatic nonischemic dilated cardiomyopathy? Author(s): Jayachandran JV, Zipes DP. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1713-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767652&dopt=Abstract
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Septal ethanol ablation for hypertrophic obstructive cardiomyopathy: early and intermediate results of a Canadian referral centre. Author(s): Bhagwandeen R, Woo A, Ross J, Wigle ED, Rakowski H, Kwinter J, Eriksson MJ, Schwartz L. Source: The Canadian Journal of Cardiology. 2003 July; 19(8): 912-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876612&dopt=Abstract
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Severe pulmonary hypertension in a patient with hypertrophic cardiomyopathy: response to alcohol septal ablation. Author(s): Brilakis ES, Nishimura RA. Source: Heart (British Cardiac Society). 2003 July; 89(7): 790. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807862&dopt=Abstract
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Severe reversible cardiomyopathy in four unrelated infants associated with mitochondrial DNA D-loop heteroplasmy. Author(s): Boles RG, Luna C, Ito M. Source: Pediatric Cardiology. 2003 September-October; 24(5): 484-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627319&dopt=Abstract
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Severe reversible dilated cardiomyopathy and hyperthyroidism: case report and review of the literature. Author(s): Boccalandro C, Boccalandro F, Orlander P, Wei CF. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2003 March-April; 9(2): 1406. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917077&dopt=Abstract
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Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy. Author(s): Fragasso G, Piatti Md PM, Monti L, Palloshi A, Setola E, Puccetti P, Calori G, Lopaschuk GD, Margonato A. Source: American Heart Journal. 2003 November; 146(5): E18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597947&dopt=Abstract
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Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Author(s): Node K, Fujita M, Kitakaze M, Hori M, Liao JK. Source: Circulation. 2003 August 19; 108(7): 839-43. Epub 2003 July 28. Erratum In: Circulation. 2003 October 28; 108(17): 2170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885745&dopt=Abstract
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Significant inducible perfusion abnormality in an asymptomatic patient with hypertrophic cardiomyopathy demonstrated by radionuclide myocardial perfusion imaging. Author(s): Loong CY, Reyes E, Underwood SR. Source: Heart (British Cardiac Society). 2003 September; 89(9): 989. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923005&dopt=Abstract
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Simultaneous vs. sequential biventricular pacing in dilated cardiomyopathy: an acute hemodynamic study. Author(s): Perego GB, Chianca R, Facchini M, Frattola A, Balla E, Zucchi S, Cavaglia S, Vicini I, Negretto M, Osculati G. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 June; 5(3): 305-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798828&dopt=Abstract
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Slowly developing heart failure associated with hormonal disorder. Late-stage acromegalic cardiomyopathy. Author(s): Harada T, Nakajima T, Kobayakawa N, Sugiura S, Nagai R. Source: J Cardiol. 2003 August; 42(2): 95-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964520&dopt=Abstract
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Specific cardiomyopathy caused by multisystemic lipid storage in Jordans' anomaly. Author(s): Nagai H, Oshima Y, Hirota H, Izumi M, Sugiyama S, Nakaoka Y, Terai K, Hasegawa S, Tateyama H, Kikui M, Yamauchi-Takihara K, Kawase I. Source: Intern Med. 2003 July; 42(7): 587-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879951&dopt=Abstract
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Stem-cell homing and tissue regeneration in ischaemic cardiomyopathy. Author(s): Franz WM, Zaruba M, Theiss H, David R. Source: Lancet. 2003 August 30; 362(9385): 675-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957085&dopt=Abstract
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Structure, stability and dynamics of the central domain of cardiac myosin binding protein C (MyBP-C): implications for multidomain assembly and causes for cardiomyopathy. Author(s): Idowu SM, Gautel M, Perkins SJ, Pfuhl M. Source: Journal of Molecular Biology. 2003 June 13; 329(4): 745-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787675&dopt=Abstract
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Subclinical skeletal muscle abnormalities in patients with hypertrophic cardiomyopathy and their relation to clinical characteristics. Author(s): Anastasakis A, Karandreas N, Stathis P, Rigopoulos A, Theopistou A, Sepp R, Elliott PM, Panagiotakos DB, Stefanadis C, Toutouzas P. Source: International Journal of Cardiology. 2003 June; 89(2-3): 249-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767549&dopt=Abstract
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Successful heart transplantation in patients with inherited myopathies associated with end-stage cardiomyopathy. Author(s): Ruiz-Cano MJ, Delgado JF, Jimenez C, Jimenez S, Cea-Calvo L, Sanchez V, Escribano P, Gomez MA, Gil-Fraguas L, Saenz de la Calzada C. Source: Transplantation Proceedings. 2003 June; 35(4): 1513-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826208&dopt=Abstract
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Sudden death of a case of hypertrophic obstructive cardiomyopathy 19 months after successful percutaneous transluminal septal myocardial ablation. Author(s): Hirata K, Wake M, Asato H, Kyushima M, Serizawa Y. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 June; 67(6): 559-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808279&dopt=Abstract
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Surgical pathology of subaortic septal myectomy associated with hypertrophic cardiomyopathy. A study of 204 cases (1996-2000). Author(s): Lamke GT, Allen RD, Edwards WD, Tazelaar HD, Danielson GK. Source: Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology. 2003 May-June; 12(3): 149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763554&dopt=Abstract
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Survival after myocardial revascularization for ischemic cardiomyopathy: a prospective ten-year follow-up study. Author(s): Shah PJ, Hare DL, Raman JS, Gordon I, Chan RK, Horowitz JD, Rosalion A, Buxton BF. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 November; 126(5): 1320-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14666002&dopt=Abstract
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Sustained cavity obliteration and apical aneurysm formation in apical hypertrophic cardiomyopathy. Author(s): Matsubara K, Nakamura T, Kuribayashi T, Azuma A, Nakagawa M. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 288-95. Erratum In: J Am Coll Cardiol. 2003 October 1; 42(7): 1338. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875766&dopt=Abstract
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Sustained improvement after combined anterior mitral leaflet extension and myectomy in hypertrophic obstructive cardiomyopathy. Author(s): van der Lee C, Kofflard MJ, van Herwerden LA, Vletter WB, ten Cate FJ. Source: Circulation. 2003 October 28; 108(17): 2088-92. Epub 2003 September 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517170&dopt=Abstract
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Tachycardiomyopathy: a diagnosis not to be missed. Author(s): Walker NL, Cobbe SM, Birnie DH. Source: Heart (British Cardiac Society). 2004 February; 90(2): E7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14729812&dopt=Abstract
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Tetralogy of Fallot with hypertrophic cardiomyopathy. Author(s): Krishnamoorthy KM, Patle A, Rao S. Source: Cardiology. 2003; 100(1): 50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975548&dopt=Abstract
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The clinical features of takotsubo cardiomyopathy. Author(s): Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Koike H, Sasaka K. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 August; 96(8): 56373. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897341&dopt=Abstract
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The correlation between expression of apoptosis-related proteins and myocardial functional reserve evaluated by dobutamine stress echocardiography in patients with dilated cardiomyopathy. Author(s): Ho YL, Chen CL, Hsu RB, Lin LC, Huang PJ. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 September; 16(9): 931-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931104&dopt=Abstract
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The epidemiology of childhood cardiomyopathy in Australia. Author(s): Nugent AW, Daubeney PE, Chondros P, Carlin JB, Cheung M, Wilkinson LC, Davis AM, Kahler SG, Chow CW, Wilkinson JL, Weintraub RG; National Australian Childhood Cardiomyopathy Study. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1639-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711738&dopt=Abstract
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The incidence of pediatric cardiomyopathy in two regions of the United States. Author(s): Lipshultz SE, Sleeper LA, Towbin JA, Lowe AM, Orav EJ, Cox GF, Lurie PR, McCoy KL, McDonald MA, Messere JE, Colan SD. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1647-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711739&dopt=Abstract
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The influence of age on gender-specific differences in the left ventricular cavity size and contractility in patients with hypertrophic cardiomyopathy. Author(s): Dimitrow PP, Czarnecka D, Kawecka-Jaszcz K, Dubiel JS. Source: International Journal of Cardiology. 2003 March; 88(1): 11-6; Discussion 16-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659978&dopt=Abstract
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The MLP family of cytoskeletal Z disc proteins and dilated cardiomyopathy: a stress pathway model for heart failure progression. Author(s): Hoshijima M, Pashmforoush M, Knoll R, Chien KR. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 399-408. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858565&dopt=Abstract
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The non-invasive assessment of hibernating myocardium in ischaemic cardiomyopathy--a myriad of techniques. Author(s): Galasko GI, Lahiri A. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 June; 5(3): 217-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798818&dopt=Abstract
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The role of coronary revascularization in the treatment of ischemic cardiomyopathy. Author(s): Lytle BW. Source: The Annals of Thoracic Surgery. 2003 June; 75(6 Suppl): S2-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820728&dopt=Abstract
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Thinned myocardial fibrosis with thrombus in the dilated form of hypertrophic cardiomyopathy demonstrated by multislice computed tomography. Author(s): Funabashi N, Yoshida K, Komuro I. Source: Heart (British Cardiac Society). 2003 August; 89(8): 858. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860857&dopt=Abstract
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Tissue Doppler imaging predicts the development of hypertrophic cardiomyopathy in subjects with subclinical disease. Author(s): Nagueh SF, McFalls J, Meyer D, Hill R, Zoghbi WA, Tam JW, Quinones MA, Roberts R, Marian AJ. Source: Circulation. 2003 July 29; 108(4): 395-8. Epub 2003 Jul 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860897&dopt=Abstract
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Tl-201 myocardial SPECT in differentiation of ischemic from nonischemic dilated cardiomyopathy in patients with left ventricular dysfunction. Author(s): Wu YW, Yen RF, Chieng PU, Huang PJ. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2003 July-August; 10(4): 369-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900741&dopt=Abstract
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Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular magnetic resonance. Author(s): Moon JC, McKenna WJ, McCrohon JA, Elliott PM, Smith GC, Pennell DJ. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742298&dopt=Abstract
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Transgenic mice overexpressing mutant PRKAG2 define the cause of WolffParkinson-White syndrome in glycogen storage cardiomyopathy. Author(s): Arad M, Moskowitz IP, Patel VV, Ahmad F, Perez-Atayde AR, Sawyer DB, Walter M, Li GH, Burgon PG, Maguire CT, Stapleton D, Schmitt JP, Guo XX, Pizard A, Kupershmidt S, Roden DM, Berul CI, Seidman CE, Seidman JG. Source: Circulation. 2003 June 10; 107(22): 2850-6. Epub 2003 Jun 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782567&dopt=Abstract
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Transient hyperinsulinism associated with macrosomia, hypertrophic obstructive cardiomyopathy, hepatomegaly, and nephromegaly. Author(s): Mehta A, Hussain K. Source: Archives of Disease in Childhood. 2003 September; 88(9): 822-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937110&dopt=Abstract
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Transient ischemic attack with apical hypertrophic cardiomyopathy. Author(s): Ceyhan C, Tekten T, Onbasili OA, Ercan E. Source: Japanese Heart Journal. 2003 March; 44(2): 285-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718490&dopt=Abstract
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Treatment of hypertrophic cardiomyopathy. Author(s): Penas-Lado M, Barriales-Villa R, Monserrat L. Source: Circulation. 2003 April 29; 107(16): E110; Auhor Reply E110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719296&dopt=Abstract
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Tumor necrosis factor-alpha polymorphism in Turkish patients with dilated cardiomyopathy. Author(s): Alikasifoglu M, Tokgozoglu L, Acil T, Atalar E, Ali Oto M, Sirri Kes S, Tuncbilek E. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 March; 5(2): 161-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644006&dopt=Abstract
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T-Wave alternans for arrhythmia risk stratification in patients with idiopathic dilated cardiomyopathy. Author(s): Verrier RL, Tolat AV, Josephson ME. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2225-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821252&dopt=Abstract
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Unusual morphologic changes in apical hypertrophic cardiomyopathy. Author(s): Fujii H, Kitakaze M, Yamagishi M. Source: Heart (British Cardiac Society). 2003 November; 89(11): 1290. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594880&dopt=Abstract
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Use of strain imaging in detecting segmental dysfunction in patients with hypertrophic cardiomyopathy. Author(s): Yang H, Sun JP, Lever HM, Popovic ZB, Drinko JK, Greenberg NL, Shiota T, Thomas JD, Garcia MJ. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 March; 16(3): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618731&dopt=Abstract
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Usefulness of 1H MR spectroscopy in the evaluation of myocardial metabolism in patients with dilated idiopathic cardiomyopathy: pilot study. Author(s): Walecki J, Michalak MJ, Michalak E, Bilinska ZT, Ruzyllo W. Source: Academic Radiology. 2003 October; 10(10): 1187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587640&dopt=Abstract
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Usefulness of microvolt T-wave alternans for prediction of ventricular tachyarrhythmic events in patients with dilated cardiomyopathy: results from a prospective observational study. Author(s): Hohnloser SH, Klingenheben T, Bloomfield D, Dabbous O, Cohen RJ. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821251&dopt=Abstract
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Usefulness of myocardial tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy. Author(s): Bax JJ, Molhoek SG, van Erven L, Voogd PJ, Somer S, Boersma E, Steendijk P, Schalij MJ, Van der Wall EE. Source: The American Journal of Cardiology. 2003 January 1; 91(1): 94-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505583&dopt=Abstract
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Utility of genetic screening in hypertrophic cardiomyopathy: prevalence and significance of novel and double (homozygous and heterozygous) beta-myosin mutations. Author(s): Mohiddin SA, Begley DA, McLam E, Cardoso JP, Winkler JB, Sellers JR, Fananapazir L. Source: Genetic Testing. 2003 Spring; 7(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820698&dopt=Abstract
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Value of heart rate variability to predict ventricular arrhythmias in recipients of prophylactic defibrillators with idiopathic dilated cardiomyopathy. Author(s): Grimm W, Herzum I, Muller HH, Christ M. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687856&dopt=Abstract
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Variable clinical manifestation of a novel missense mutation in the alphatropomyosin (TPM1) gene in familial hypertrophic cardiomyopathy. Author(s): Jongbloed RJ, Marcelis CL, Doevendans PA, Schmeitz-Mulkens JM, Van Dockum WG, Geraedts JP, Smeets HJ. Source: Journal of the American College of Cardiology. 2003 March 19; 41(6): 981-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651045&dopt=Abstract
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Varieties of right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy. Author(s): Komaki K, Sakuma M, Ishigaki H, Hozawa H, Yamamoto Y, Takahashi T, Kumasaka N, Kagaya Y, Ikeda J, Watanabe J, Shirato K. Source: The Tohoku Journal of Experimental Medicine. 2003 January; 199(1): 49-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688560&dopt=Abstract
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Ventricular dyssynchrony and risk markers of ventricular arrhythmias in nonischemic dilated cardiomyopathy: a study with phase analysis of angioscintigraphy. Author(s): Fauchier L, Marie O, Casset-Senon D, Babuty D, Cosnay P, Fauchier JP. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 352-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687844&dopt=Abstract
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Ventricular expression of atrial natriuretic peptide in chronic chagasic cardiomyopathy is not induced by myocarditis. Author(s): Benvenuti LA, Aiello VD, Palomino SA, Higuchi Mde L. Source: International Journal of Cardiology. 2003 March; 88(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12659985&dopt=Abstract
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Ventricular long axis function is predictive of outcome in patients with chronic heart failure secondary to non-ischemic dilated cardiomyopathy. Author(s): Faris R, Henein MY, Coats AJ. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 November; 9(11): Cr456-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586270&dopt=Abstract
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Ventricular reconstruction for ischemic cardiomyopathy. Author(s): Mickleborough LL, Merchant N, Provost Y, Carson S, Ivanov J. Source: The Annals of Thoracic Surgery. 2003 June; 75(6 Suppl): S6-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820729&dopt=Abstract
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Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Author(s): Hagege AA, Carrion C, Menasche P, Vilquin JT, Duboc D, Marolleau JP, Desnos M, Bruneval P. Source: Lancet. 2003 February 8; 361(9356): 491-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583951&dopt=Abstract
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Visualization of myocardial perfusion after percutaneous myocardial septal ablation for hypertrophic cardiomyopathy using superharmonic imaging. Author(s): Ten Cate FJ, Bouakaz A, Krenning B, Vletter W, de Jong N. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 April; 16(4): 370-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712021&dopt=Abstract
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What is the mechanism of abnormal blood pressure response on exercise in hypertrophic cardiomyopathy? Author(s): Campbell R, Manyari DE, McKenna WJ, Frenneaux M. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2102; Author Reply 2102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798589&dopt=Abstract
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Who and how to treat with non-surgical myocardial reduction therapy in hypertrophic cardiomyopathy: long-term outcomes. Author(s): Martin WA, Sigwart U. Source: Heart Fail Monit. 2002; 3(1): 15-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634884&dopt=Abstract
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CHAPTER 2. NUTRITION AND CARDIOMYOPATHY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and cardiomyopathy.
Finding Nutrition Studies on Cardiomyopathy 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 “cardiomyopathy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “cardiomyopathy” (or a synonym): •
A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. Author(s): The Hospital for Rheumatic Diseases, Hanyang University, 17 Haengdongdong, Seongdong-gu, Seoul 133-792, Korea. Source: Lee, Seung Won Kim, Ki Chan Oh, Dong Ho Jung, Sung Soo Yoo, Dae Hyun Kim, Seong Yoon Choe, Gheeyoung Kim, Tae Hwan J-Korean-Med-Sci. 2002 February; 17(1): 141-3 1011-8934
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A rat model of dilated cardiomyopathy to investigate partial left ventriculectomy. Author(s): Department of Cardiovascular Surgery, Matsue Red-Cross Hospital, Shimane, Japan. Source: Yuasa, S Nishina, T Nishimura, K Miwa, S Ikeda, T Hanyu, M Fujioka, Y Kihara, Y Sasayama, S Komeda, M J-Card-Surg. 2001 Jan-February; 16(1): 40-7 0886-0440
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A rat model of ischaemic or dilated cardiomyopathy for investigating left ventricular repair surgery. Author(s): Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Source: Nishina, T Miwa, S Yuasa, S Nishimura, K Komeda, M Clin-Exp-PharmacolPhysiol. 2002 August; 29(8): 728-30 0305-1870
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Activity of GH/IGF-I axis in patients with dilated cardiomyopathy. Author(s): Department of Internal Medicine, University of Turin, Italy. Source: Benso, A Broglio, F Gottero, C Di Vito, L Arvat, E Bobbio, M Ghigo, E JEndocrinol-Invest. 1999; 22(10 Suppl): 63 0391-4097
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Advances in the treatment of dilated cardiomyopathy. Source: Purcell, J A AACN-Clin-Issues-Crit-Care-Nurs. 1990 May; 1(1): 31-45 1046-7467
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Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene, OCTN2. Author(s): Department of Hygiene, Akita University School of Medicine, Japan. Source: Xiaofei, E Wada, Yasuhiko Dakeishi, Miwako Hirasawa, Fujiko Murata, Katsuyuki Masuda, Hirotake Sugiyama, Toshihiro Nikaido, Hiroko Koizumi, Akio JGerontol-A-Biol-Sci-Med-Sci. 2002 July; 57(7): B270-8 1079-5006
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Alcohol-induced congestive cardiomyopathy in adult turkeys: effects on myocardial antioxidant defence systems. Author(s): 2nd Department of Medicine, University Medical School, Szeged, Hungary. Source: Edes, I Piros, G Forster, T Csanady, M Basic-Res-Cardiol. 1987 Nov-December; 82(6): 551-6 0300-8428
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Anticoagulation in patients with dilated cardiomyopathy and sinus rhythm: a critical literature review. Author(s): Division of Cardiovascular Diseases, Department of Internal Medicine, University of Florida Health Science Center, Jacksonville, FL, USA. Source: Sirajuddin, Riaz A Miller, Alan B Geraci, Stephen A J-Card-Fail. 2002 February; 8(1): 48-53 1071-9164
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Axillary vein thrombosis complicating peripartum congestive cardiomyopathy. Source: Neill, P Cent-Afr-J-Med. 1987 December; 33(12): 292-4 0008-9176
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beta-Methyl-p-(123I)-iodophenyl pentadecanoic acid single-photon emission computed tomography in cardiomyopathy. Author(s): Osaka University, Medical School, Japan.
[email protected]
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Source: Nishimura, T Int-J-Card-Imaging. 1999 February; 15(1): 41-8 0167-9899 •
Calcium-activated protease in hamster cardiomyopathy. Source: Spalla, M Kuo, T H Wiener, J Muscle-Nerve. 1987 January; 10(1): 54-9 0148-639X
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Cardiac thrombus in dilated cardiomyopathy. Relationship between left ventricular pathophysiology and left ventricular thrombus. Author(s): First Department of Internal Medicine, Kobe University School of Medicine, Japan. Source: Yokota, Y Kawanishi, H Hayakawa, M Kumaki, T Takarada, A Nakanishi, O Fukuzaki, H Jpn-Heart-J. 1989 January; 30(1): 1-11 0021-4868
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Cardiomyopathy in children. Author(s): Department of Pediatrics, University of South Florida, Tampa, USA. Source: Gilbert Barness, E Marshall, R J W-V-Med-J. 2000 Jan-February; 96(1): 352-6 0043-3284
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Contractile responses of myocytes isolated from patients with cardiomyopathy. Author(s): Department of Cardiac Medicine, National Heart and Lung Institute, London, U.K. Source: Harding, S E MacLeod, K T Jones, S M Vescovo, G Poole Wilson, P A Eur-HeartJ. 1991 August; 12 Suppl D44-8 0195-668X
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Coronary flow reserve in patients with chest pain, angiographically normal coronary arteries and normal left ventricle, dilated cardiomyopathy, and hypertrophic cardiomyopathy. Author(s): Cardiovascular Diagnosis Section, National Heart, Lung, and Blood Institute, Bethesda, Md. Source: Cannon, R O 3rd Bibl-Cardiol. 1989; (44): 25-38; discussion 38-9 0067-7906
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Dilated cardiomyopathy in an American Cocker Spaniel with taurine deficiency. Source: Gavaghan, B.J. Kittleson, M.D. Aust-vet-j. Brunswick, Vic. : Australian Veterinary Association, 1927-. December 1997. volume 75 (12) page 862-868. 0005-0423
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Echocardiographic features of genetic diseases: part 1. Cardiomyopathy. Author(s): Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. Source: Alizad, A Seward, J B J-Am-Soc-Echocardiogr. 2000 January; 13(1): 73-86 08947317
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Experimental induction of cardiomyopathy in young bovine. Source: Kennedy, S. Rice, D.A. McMurray, C.H. Selenium in biology and medicine : proceedings of the Third International Symposium on Selenium in Biology and Medicine, held May 27-June 1, 1984, Xiangshan (Fragrance Hills) Hotel Beijing, People's Republic of China. New York : Van Nostrand Reinhold, c1987. page 853-856. ill. ISBN: 0442221088
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Familial hypertrophic cardiomyopathy and muscle carnitine deficiency. Author(s): Department of Neurology, Hospital Virgen del Rocio, Sevilla, Spain. Source: Bautista, J Rafel, E Martinez, A Sainz, I Herrera, J Segura, L Chinchon, I MuscleNerve. 1990 Mar; 13(3): 192-4 0148-639X
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Fulminant heart failure due to selenium deficiency cardiomyopathy (Keshan disease). Author(s): Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash University, Southbank, Australia. Source: Burke, Michael Philip Opeskin, Kenneth Med-Sci-Law. 2002 January; 42(1): 10-3 0025-8024
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Glucose insulin potassium infusion improves systolic function in patients with chronic ischemic cardiomyopathy. Author(s): Cardiology Department, University Hospital, Dijon, France.
[email protected] Source: Cottin, Yves Lhuillier, Isabelle Gilson, Laurent Zeller, Marianne Bonnet, Caroline Toulouse, Christine Louis, Pierre Rochette, Luc Girard, Claude Wolf, Jean Eric Eur-J-Heart-Fail. 2002 Mar; 4(2): 181-4 1388-9842
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Growth hormone therapy in dilated cardiomyopathy monitored with MRI. Author(s): Franz-Volhard-Klinik, Max-Delbruck-Centrum for Molecular Medicine, Charite, Humboldt-University, Berlin, Germany. Source: Friedrich, M G Strohm, O Osterziel, K J Dietz, R MAGMA. 1998 September; 6(23): 152-4 0968-5243
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Growth hormone treatment in dilated cardiomyopathy. Author(s): Charitz/Franz-Volhard-Klinik am Max Delbruck Centrum fur Molekulare Medizin, Humboldt Universitat zu Berlin, Germany.
[email protected] Source: Perrot, A Ranke, M B Dietz, R Osterziel, K J J-Card-Surg. 2001 Mar-April; 16(2): 127-31 0886-0440
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Heart failure and Ca++ activation of the cardiac contractile system: hereditary cardiomyopathy in hamsters (BIO 14.6), isoprenaline overload and the effect of APP 201-533. Author(s): Department Research CVS, Ciba-Geigy Ltd., Basle, Switzerland. Source: Herzig, J W Gerber, W Salzmann, R Basic-Res-Cardiol. 1987 Jul-August; 82(4): 326-40 0300-8428
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Idiopathic dilated cardiomyopathy presenting in pregnancy. Author(s): Department of Anaesthesia & Intensive Care, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, China. Source: Chan, F Ngan Kee, W D Can-J-Anaesth. 1999 December; 46(12): 1146-9 0832610X
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Lack of effects of recombinant human growth hormone in a child with a complex cardiovascular malformation and dilated cardiomyopathy. Author(s): Cardiologia/Cardiochirurgia Pediatrica, Centro “E. Malan”, Ospedale San Donato, San Donato Milanese, Milano, Italy. Source: Rosti, L Cerini, E Festa, P Miola, A Brunelli, V Frigiola, A J-Endocrinol-Invest. 2000 January; 23(1): 28-30 0391-4097
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L-carnitine in children with idiopathic dilated cardiomyopathy. Author(s): Department of Cardiology, All India Institute of Medical Sciences, New Delhi. Source: Kothari, S S Sharma, M Indian-Heart-J. 1998 Jan-February; 50(1): 59-61 0019-4832
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Life-style related factors and idiopathic dilated cardiomyopathy--a case-control study using pooled controls. Author(s): Kurume University Medical Center, Japan. Source: Kodama, K Toshima, H Yazaki, Y Toyoshima, H Nakagawa, H Okada, R Kitabatake, A Serizawa, T Tanaka, H Hosoda, S Yano, K Yokoyama, M Fujita, Y Kasagi, F Yokoyama, T Tanaka, H Kawamura, T Ohno, Y Hashimoto, T J-Epidemiol. 1999 November; 9(5): 286-96 0917-5040
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Medical therapy of end-stage congestive and ischemic cardiomyopathy. Source: Leier, C V Unverferth, D V Cardiovasc-Clin. 1988; 19(1): 243-51 0069-0384
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Monocyte chemoattractant protein 1 (MCP-1) gene expression in dilated cardiomyopathy. Author(s): Department of Internal Medicine, Division of Cardiology, University of Jena, Jena, Germany. Source: Lehmann, M H Kuhnert, H Muller, S Sigusch, H H Cytokine. 1998 October; 10(10): 739-46 1043-4666
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Nemaline myopathy and cardiomyopathy. Author(s): Department of Pediatric Cardiology, University of Vienna, Austria. Source: Skyllouriotis, M L Marx, M Skyllouriotis, P Bittner, R Wimmer, M PediatrNeurol. 1999 April; 20(4): 319-21 0887-8994
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Opioid peptides in response to mental stress in asymptomatic dilated cardiomyopathy. Author(s): Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Ospedale S. Orsola, Bologna, Italy. Source: Fontana, F Bernardi, P Merlo Pich, E Tartuferi, L Boschi, S De Iasio, R Spampinato, S Peptides. 1998; 19(7): 1147-53 0196-9781
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Possible involvement of free radicals and antioxidants in the early stages of the development of cardiomyopathy in BIO 14.6 Syrian Hamster. Author(s): Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan. Source: Fukuchi, T Kobayashi, A Kaneko, M Ichiyama, A Yamazaki, N Jpn-Heart-J. 1991 September; 32(5): 655-66 0021-4868
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Pregnancy and peripartum cardiomyopathy. A comparative and prospective study. Author(s): Instituto do Coracao do Hospital das Clinicas - FMUSP, Sao Paulo, Brazil.
[email protected] Source: Avila, W S de Carvalho, M E Tschaen, C K Rossi, E G Grinberg, M Mady, C Ramires, J A Arq-Bras-Cardiol. 2002 November; 79(5): 484-93 0066-782X
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Primary systemic carnitine deficiency presenting as recurrent Reye-like syndrome and dilated cardiomyopathy. Author(s): Division of Medical Genetics, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan, ROC. Source: Hou, J W Chang-Gung-Med-J. 2002 December; 25(12): 832-7
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Propionyl-L-carnitine as protector against adriamycin-induced cardiomyopathy. Author(s): Pharmacology Unit, National Cancer Institute, Fum El-Khalig, Kasr El-Aini Street, Cairo, Egypt. Source: Sayed Ahmed, M M Salman, T M Gaballah, H E Abou El Naga, S A Nicolai, R Calvani, M Pharmacol-Res. 2001 June; 43(6): 513-20 1043-6618
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Protection from adriamycin-induced cardiomyopathy in rats. Author(s): Metabolic Research Laboratory, William S. Middleton Memorial Veterans Administration Hospital, Madison. Source: Shug, A L Z-Kardiol. 1987; 76 Suppl 546-52 0300-5860
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Rationale for clinical trials of selenium as an antioxidant for the treatment of the cardiomyopathy of Friedreich's ataxia. Author(s): John Tabor Laboratories, University of Essex, Colchester, UK.
[email protected] Source: Fryer, M J Med-Hypotheses. 2002 February; 58(2): 127-32 0306-9877
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Recirculating, retrograde heart perfusion according to Langendorff as a tool in the evaluation of drug-induced cardiomyopathy: effects of a high lipid diet. Author(s): Institute of Toxicology, Swiss Federal Institute of Technology. Source: Bachmann, E Weber, E Arch-Toxicol. 1991; 65(6): 474-9 0340-5761
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Relationship between dietary fatty acid, selenium, and degenerative cardiomyopathy. Author(s): Kenneth L. Jordan Heart Fund, Montclair, NJ. Source: Bierenbaum, M L Chen, Y Lei, H Watkins, T Med-Hypotheses. 1992 September; 39(1): 58-62 0306-9877
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Serum antioxidant capacity in neurological, psychiatric, renal diseases and cardiomyopathy. Author(s): Neuroscience and Phytochemical Laboratories, Jean Mayer USDA Human Nutrition Research Center on Aging, Tuft's University, Boston, MA, USA. Source: Sofic, E Rustembegovic, A Kroyer, G Cao, G J-Neural-Transm. 2002 May; 109(56): 711-9 0300-9564
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Serum selenium deficiency in myocardial infarction and congestive cardiomyopathy. Author(s): Unit of Cardiology, Bicetre Hospital, Paris. Source: Auzepy, P Blondeau, M Richard, C Pradeau, D Therond, P Thuong, T ActaCardiol. 1987; 42(3): 161-6 0001-5385
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Structural manifestations of diabetic cardiomyopathy in the rat and its reversal by insulin treatment. Author(s): Hornel Institute, University of Minnesota, Austin 55912. Source: Thompson, E W Am-J-Anat. 1988 July; 182(3): 270-82 0002-9106
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Sympathetic deactivation by growth hormone treatment in patients with dilated cardiomyopathy. Author(s): Department of Internal Medicine, IRCCS, NEUROMED, Pozzilli Isernia, Italy. Source: Capaldo, B Lembo, G Rendina, V Vigorito, C Guida, R Cuocolo, A Fazio, S Sacca, L Eur-Heart-J. 1998 April; 19(4): 623-7 0195-668X
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The addition of pentoxifylline to conventional therapy improves outcome in patients with peripartum cardiomyopathy. Author(s): Department of Cardiology, Baragwanath Hospital, University of the Witwatersrand, PO Bertsham 2013, Johannesburg, South Africa.
[email protected] Source: Sliwa, K Skudicky, D Candy, G Bergemann, A Hopley, M Sareli, P Eur-J-HeartFail. 2002 June; 4(3): 305-9 1388-9842
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The effects of L-carnitine treatment on left ventricular function and erythrocyte superoxide dismutase activity in patients with ischemic cardiomyopathy. Author(s): Department of Cardiology, Ankara University Faculty of Medicine, Ankara, Turkey. Source: Gurlek, A Tutar, E Akcil, E Dincer, I Erol, C Kocaturk, P A Oral, D Eur-J-HeartFail. 2000 June; 2(2): 189-93 1388-9842
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The role of selenium deficiency in occidental dilated cardiomyopathy. Author(s): Cardiology Department, Princess Margaret Hospital, Christchurch. Source: Ikram, H Crozier, I G Webster, M Low, C J N-Z-Med-J. 1989 March 8; 102(863): 100-2 0028-8446
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The role of the carnitine system in myocardial fatty acid oxidation: carnitine deficiency, failing mitochondria and cardiomyopathy. Author(s): Department of Biochemistry, Medical Faculty, Erasmus University, Rotterdam, The Netherlands.
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Source: Scholte, H R Luyt Houwen, I E Vaandrager Verduin, M H Basic-Res-Cardiol. 1987; 82 Suppl 163-73 0300-8428 •
The use of enalapril in the treatment of feline hypertrophic cardiomyopathy. Source: Rush, J.E. Freeman, L.M. Brown, D.J. Smith, F.W.K. Jr. J-Am-Anim-Hosp-Assoc. Lakewood, Colo. : The American Animal Hospital Association. Jan/February 1998. volume 34 (1) page 38-41. 0587-2871
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Thiamin, selenium, and copper levels in patients with idiopathic dilated cardiomyopathy taking diuretics. Author(s): Hospital Universitario Pedro Ernesto, IBRAG, Geologia - UERJ, Rio de Janeiro, RJ, Brazil.
[email protected] Source: da Cunha, S Albanesi Filho, F M da Cunha Bastos, V L Antelo, D S Souza, M M Arq-Bras-Cardiol. 2002 November; 79(5): 454-65 0066-782X
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To anticoagulate or not to anticoagulate patients with cardiomyopathy. Author(s): Division of Cardiology, Department of Medicine, State University of New York at Buffalo, Buffalo General Hospital, Buffalo, New York, USA.
[email protected] Source: Graham, S P Cardiol-Clin. 2001 November; 19(4): 605-15 0733-8651
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Transient dilated cardiomyopathy in a newborn exposed to idarubicin and all-transretinoic acid (ATRA) early in the second trimester of pregnancy. Author(s): Department of Pediatrics (Cardiology), Texas Children's Hospital, 6621 Fannin, MC 19345-C, Houston, TX 77030, USA. Source: Siu, B L Alonzo, M R Vargo, T A Fenrich, A L Int-J-Gynecol-Cancer. 2002 JulAugust; 12(4): 399-402 1048-891X
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Treatment of advanced heart failure in a young man with familial cardiomyopathy. Author(s): Department of Adult Cardiology, Texas Heart Institute, St. Luke's Episcopal Hospital, Houston 77030, USA. Source: Massin, E K Tex-Heart-Inst-J. 1998; 25(4): 294-7 0730-2347
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Use of dexrazoxane and other strategies to prevent cardiomyopathy associated with doxorubicin-taxane combinations. Author(s): Albert Einstein Cancer Center, Montefiore Medical Center, Bronx, NY 10467, USA. Source: Sparano, J A Semin-Oncol. 1998 August; 25(4 Suppl 10): 66-71 0093-7754
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Value of radionuclide assessment with thallium 201 scintigraphy in carnitine deficiency cardiomyopathy. Author(s): Service de Pediatrie Hopital Herold, Paris, France. Source: Taillard, F Mundler, O Tillous Borde, I Desbois, J C Paturneau Jouas, M EurHeart-J. 1988 July; 9(7): 811-8 0195-668X
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Warfarin for dilated cardiomyopathy: a bloody tough pill to swallow? Author(s): Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111. Source: Tsevat, J Eckman, M H McNutt, R A Pauker, S G Med-Decis-Making. 1989 JulSeptember; 9(3): 162-9 0272-989X
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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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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to cardiomyopathy; 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 B1 Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com L-carnitine Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE CARDIOMYOPATHY
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to cardiomyopathy. 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 cardiomyopathy 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 “cardiomyopathy” (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 cardiomyopathy: •
A cohort study of childhood hypertrophic cardiomyopathy: improved survival following high-dose beta-adrenoceptor antagonist treatment. Author(s): Ostman-Smith I, Wettrell G, Riesenfeld T. Source: Journal of the American College of Cardiology. 1999 November 15; 34(6): 181322. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10577575&dopt=Abstract
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A physiological oral magnesium supplement does not influence total serum magnesium, left ventricular ejection fraction and prognosis in patients with dilated cardiomyopathy. Author(s): Fruhwald FM, Dusleag J, Fruhwald SM, Grisold M, Gasser R, Klein W. Source: Magnes Res. 1993 September; 6(3): 251-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8292499&dopt=Abstract
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Alteration of Na,K-ATPase isoenzymes in diabetic cardiomyopathy: effect of dietary supplementation with fish oil (n-3 fatty acids) in rats. Author(s): Gerbi A, Barbey O, Raccah D, Coste T, Jamme I, Nouvelot A, Ouafik L, Levy S, Vague P, Maixent JM. Source: Diabetologia. 1997 May; 40(5): 496-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9165216&dopt=Abstract
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Arrhythmogenic right ventricular cardiomyopathy and sudden cardiac death in young Koreans. Author(s): Cho Y, Park T, Yang DH, Park HS, Chae J, Chae SC, Jun JE, Kwak JS, Park WH. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2003 November; 67(11): 925-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14578598&dopt=Abstract
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Cardiomyopathies and oxidative stress. Author(s): Romero-Alvira D, Roche E, Placer L. Source: Medical Hypotheses. 1996 August; 47(2): 137-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8869930&dopt=Abstract
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Cardiomyopathy from ipecac administration in Munchausen syndrome by proxy. Author(s): Goebel J, Gremse DA, Artman M. Source: Pediatrics. 1993 October; 92(4): 601-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8105444&dopt=Abstract
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Cardiomyopathy of copper deficiency: effect of vitamin E supplementation. Author(s): Fields M, Lewis CG, Lure MD. Source: Journal of the American College of Nutrition. 1992 June; 11(3): 330-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1619185&dopt=Abstract
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Clinical and pathologic aspects of cardiomyopathy from ipecac administration in Munchausen's syndrome by proxy. Author(s): Schneider DJ, Perez A, Knilamus TE, Daniels SR, Bove KE, Bonnell H. Source: Pediatrics. 1996 June; 97(6 Pt 1): 902-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8657536&dopt=Abstract
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Dietary fish oil does not prevent doxorubicin-induced cardiomyopathy in rats. Author(s): Matsui H, Morishima I, Hayashi K, Kamiya H, Saburi Y, Okumura K. Source: The Canadian Journal of Cardiology. 2002 March; 18(3): 279-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907617&dopt=Abstract
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Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid. Author(s): Ostman-Smith I, Brown G, Johnson A, Land JM. Source: British Heart Journal. 1994 October; 72(4): 349-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7833193&dopt=Abstract
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Dilated cardiomyopathy in juvenile chronic arthritis. Author(s): Soylemezoglu O, Besbas N, Ozkutlu S, Saatci U. Source: Scandinavian Journal of Rheumatology. 1994; 23(3): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8016592&dopt=Abstract
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Echocardiographic findings of the heart resembling dilated cardiomyopathy during hypokalemic myopathy due to licorice-induced pseudoaldosteronism. Author(s): Hasegawa J, Suyama Y, Kinugawa T, Morisawa T, Kishimoto Y. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1998 December; 12(6): 599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10410830&dopt=Abstract
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Ephedra-associated cardiomyopathy. Author(s): Naik SD, Freudenberger RS. Source: The Annals of Pharmacotherapy. 2004 March; 38(3): 400-3. Epub 2004 January 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14742827&dopt=Abstract
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Experimental idiopathic dilated cardiomyopathy under low-calcium condition. Author(s): Yamaguchi H, Kaku H, Onodera T, Kurokawa R, Morisada M. Source: Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Fur Toxikologische Pathologie. 1994 August; 46(3): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8000243&dopt=Abstract
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Genotypic and serotypic profile in dilated cardiomyopathy. Author(s): Wesslen L, Waldenstrom A, Lindblom B, Hoyer S, Friman G, Fohlman J. Source: Scand J Infect Dis Suppl. 1993; 88: 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8390721&dopt=Abstract
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Hypertrophic obstructive cardiomyopathy: alternative therapeutic options. Author(s): Cheng TO. Source: Clin Cardiol. 1997 July; 20(7): 667. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220187&dopt=Abstract
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Impaired cardiac adrenergic innervation assessed by MIBG imaging as a predictor of treatment response in childhood dilated cardiomyopathy. Author(s): Acar P, Merlet P, Iserin L, Bonnet D, Sidi D, Syrota A, Kachaner J.
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Source: Heart (British Cardiac Society). 2001 June; 85(6): 692-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359754&dopt=Abstract •
Induction of subaortic septal ischaemia to reduce obstruction in hypertrophic obstructive cardiomyopathy. Studies to develop a new catheter-based concept of treatment. Author(s): Kuhn H, Gietzen F, Leuner C, Gerenkamp T. Source: European Heart Journal. 1997 May; 18(5): 846-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9152655&dopt=Abstract
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Interferon and thymic hormones in the therapy of human myocarditis and idiopathic dilated cardiomyopathy. Author(s): Miric M, Miskovic A, Vasiljevic JD, Keserovic N, Pesic M. Source: European Heart Journal. 1995 December; 16 Suppl O: 150-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8682086&dopt=Abstract
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Ipecac myopathy and cardiomyopathy. Author(s): Dresser LP, Massey EW, Johnson EE, Bossen E. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1993 May; 56(5): 560-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8099367&dopt=Abstract
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Iron overload cardiomyopathies: new insights into an old disease. Author(s): Liu P, Olivieri N. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1994 February; 8(1): 101-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8086319&dopt=Abstract
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L-carnitine administration in coronary artery disease and cardiomyopathy. Author(s): Singh RB, Aslam M. Source: J Assoc Physicians India. 1998 September; 46(9): 801-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229253&dopt=Abstract
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L-carnitine supplementation in the therapy of canine dilated cardiomyopathy. Author(s): Keene BW. Source: The Veterinary Clinics of North America. Small Animal Practice. 1991 September; 21(5): 1005-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1949496&dopt=Abstract
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Long-term follow-up of patients with myocarditis and idiopathic cardiomyopathy after immunomodulatory therapy. Author(s): Miric M, Miskovic A, Brkic S, Vasiljevic J, Keserovic N, Pesic M.
dilated
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Source: Fems Immunology and Medical Microbiology. 1994 November; 10(1): 65-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7874080&dopt=Abstract •
Long-term survival effect of metoprolol in dilated cardiomyopathy. The SPIC (Italian Multicentre Cardiomyopathy Study) Group. Author(s): Di Lenarda A, De Maria R, Gavazzi A, Gregori D, Parolini M, Sinagra G, Salvatore L, Longaro F, Bernobich E, Camerini F. Source: Heart (British Cardiac Society). 1998 April; 79(4): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9616339&dopt=Abstract
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Magnesium status and the effect of magnesium supplementation in feline hypertrophic cardiomyopathy. Author(s): Freeman LM, Brown DJ, Smith FW, Rush JE. Source: Canadian Journal of Veterinary Research = Revue Canadienne De Recherche Veterinaire. 1997 July; 61(3): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9243004&dopt=Abstract
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Metabolic aspects of myocardial disease and a role for L-carnitine in the treatment of childhood cardiomyopathy. Author(s): Helton E, Darragh R, Francis P, Fricker FJ, Jue K, Koch G, Mair D, Pierpont ME, Prochazka JV, Linn LS, Winter SC. Source: Pediatrics. 2000 June; 105(6): 1260-70. Erratum In: Pediatrics 2000 September; 106(3): 623. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10835067&dopt=Abstract
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Nonsurgical septal reduction therapy for hypertrophic obstructive cardiomyopathy: one-year follow-up. Author(s): Lakkis NM, Nagueh SF, Dunn JK, Killip D, Spencer WH 3rd. Source: Journal of the American College of Cardiology. 2000 September; 36(3): 852-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987610&dopt=Abstract
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Rapidly reversible cardiomyopathy associated with chronic ipecac ingestion. Author(s): Ho PC, Dweik R, Cohen MC. Source: Clin Cardiol. 1998 October; 21(10): 780-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9789704&dopt=Abstract
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Relationship between dietary fatty acid, selenium, and degenerative cardiomyopathy. Author(s): Bierenbaum ML, Chen Y, Lei H, Watkins T. Source: Medical Hypotheses. 1992 September; 39(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1435394&dopt=Abstract
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Response of cats with dilated cardiomyopathy to taurine supplementation. Author(s): Pion PD, Kittleson MD, Thomas WP, Delellis LA, Rogers QR.
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Source: J Am Vet Med Assoc. 1992 July 15; 201(2): 275-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1500324&dopt=Abstract •
Reversal of Borrelia burgdorferi associated dilated cardiomyopathy by antibiotic treatment? Author(s): Gasser R, Fruhwald F, Schumacher M, Seinost G, Reisinger E, Eber B, Keplinger A, Horvath R, Sedaj B, Klein W, Pierer K. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1996 July; 10(3): 351-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8877079&dopt=Abstract
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Reversal of haemochromatotic cardiomyopathy in beta thalassaemia by chelation therapy. Author(s): Politi A, Sticca M, Galli M. Source: British Heart Journal. 1995 May; 73(5): 486-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7786668&dopt=Abstract
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Reversible dilated cardiomyopathy following treatment of atopic eczema with Chinese herbal medicine. Author(s): Ferguson JE, Chalmers RJ, Rowlands DJ. Source: The British Journal of Dermatology. 1997 April; 136(4): 592-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9155965&dopt=Abstract
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Reversible restrictive cardiomyopathy due to light-chain deposition disease. Author(s): Nakamura M, Satoh M, Kowada S, Satoh H, Tashiro A, Sato F, Masuda T, Hiramori K. Source: Mayo Clinic Proceedings. 2002 February; 77(2): 193-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838655&dopt=Abstract
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Right ventricular cardiomyopathy in beta-thalassaemia major. Author(s): Hahalis G, Manolis AS, Apostolopoulos D, Alexopoulos D, Vagenakis AG, Zoumbos NC. Source: European Heart Journal. 2002 January; 23(2): 147-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11785997&dopt=Abstract
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Role of endothelin-1 in the development of a special type of cardiomyopathy. Author(s): Zsary A, Szucs S, Schneider T, Rosta A, Sarman P, Fenyvesi T, Karadi I. Source: Clinical Science (London, England : 1979). 2002 August; 103 Suppl 48: 272S-275S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193102&dopt=Abstract
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Secondary and Infiltrative Cardiomyopathies. Author(s): Saltzberg MT.
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Source: Current Treatment Options in Cardiovascular Medicine. 2000 October; 2(5): 373384. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096542&dopt=Abstract •
Selenium deficiency associated with cardiomyopathy: a complication of the ketogenic diet. Author(s): Bergqvist AG, Chee CM, Lutchka L, Rychik J, Stallings VA. Source: Epilepsia. 2003 April; 44(4): 618-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681013&dopt=Abstract
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Successful treatment with an implantable cardioverter defibrillator for spontaneous ventricular fibrillation in dilated cardiomyopathy with very high defibrillation thresholds. Author(s): Tamura K, Abe H, Nagatomo T, Nakashima Y. Source: J Uoeh. 2001 December 1; 23(4): 363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789138&dopt=Abstract
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The effect of EGb 761 on the doxorubicin cardiomyopathy. Author(s): Timioglu O, Kutsal S, Ozkur M, Uluoglu O, Aricioglu A, Cevik C, Duzgun E, Sancak B, Poyraz A. Source: Res Commun Mol Pathol Pharmacol. 1999; 106(3): 181-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485048&dopt=Abstract
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Use of dexrazoxane and other strategies to prevent cardiomyopathy associated with doxorubicin-taxane combinations. Author(s): Sparano JA. Source: Seminars in Oncology. 1998 August; 25(4 Suppl 10): 66-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9768827&dopt=Abstract
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Use of paclitaxel in patients with pre-existing cardiomyopathy: a review of our experience. Author(s): Gollerkeri A, Harrold L, Rose M, Jain D, Burtness BA. Source: International Journal of Cancer. Journal International Du Cancer. 2001 July 1; 93(1): 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391633&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to cardiomyopathy; 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 Ascariasis Source: Integrative Medicine Communications; www.drkoop.com Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Cardiomyopathy Source: Prima Communications, Inc.www.personalhealthzone.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Guinea Worm Disease Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hookworm Source: Integrative Medicine Communications; www.drkoop.com
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Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Loiasis Source: Integrative Medicine Communications; www.drkoop.com Lymphatic Filariasis Source: Integrative Medicine Communications; www.drkoop.com Pinworm Source: Integrative Medicine Communications; www.drkoop.com River Blindness Source: Integrative Medicine Communications; www.drkoop.com Roundworms Source: Integrative Medicine Communications; www.drkoop.com Shock Source: Integrative Medicine Communications; www.drkoop.com Threadworm Source: Integrative Medicine Communications; www.drkoop.com Trichinosis Source: Integrative Medicine Communications; www.drkoop.com Visceral Larva Migrans Source: Integrative Medicine Communications; www.drkoop.com Whipworm Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc.www.personalhealthzone.com Coleus Alternative names: Coleus forskohlii Source: Healthnotes, Inc.; www.healthnotes.com Doxorubicin Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Hawthorn Alternative names: Crataegus laevigata, Crataegus oxyacantha, Crataegus monogyna Source: Healthnotes, Inc.; www.healthnotes.com Taurine Source: Healthnotes, Inc.; www.healthnotes.com Thymus Extracts Source: Healthnotes, Inc.; www.healthnotes.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON CARDIOMYOPATHY Overview In this chapter, we will give you a bibliography on recent dissertations relating to cardiomyopathy. 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 “cardiomyopathy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cardiomyopathy, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Cardiomyopathy 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 cardiomyopathy. 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: •
Cardiac Vasoactive Peptides in Hypertrophic Cardiomyopathy of Cats by Biondo, Alexander Welker, PhD from University of Illinois at Urbana-Champaign, 2003, 140 pages http://wwwlib.umi.com/dissertations/fullcit/3101799
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Effects of Pkc Phosphorylation and Mutations Linked to Familial Hypertrophic Cardiomyopathy in the Heart by Burkart, Eileen Marie, PhD from University of Illinois at Chicago, Health Sciences Center, 2003, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3098349
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Erbb2 Is Essential for Maintenance of the Enteric Nervous System and Prevention of Dilated Cardiomyopathy by Crone, Steven Allen, PhD from University of California, San Diego, 2003, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3071016
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Excitation-contraction Coupling in Hamster Model of Cardiomyopathy by Ma, Tony Sungnan; PhD from The University of Manitoba (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK37811
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Initiation and Progression of Cardiomyopathy in Sarcoglycan Deficiency by Wheeler, Matthew Thomas, PhD from The University of Chicago, 2003, 250 pages http://wwwlib.umi.com/dissertations/fullcit/3097182
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Investigations of the Mechanism of Alcohol-induced Cardiomyopathy by King, David Christopher; PhD from The University of Western Ontario (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL49328
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Pathophysiology of Bacterial Cardiomyopathy by Tomlinson, Charles W; PhD from The University of Manitoba (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK26385
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Retrovirally Induced Dilated Cardiomyopathy in Murine Acquired Immunodeficiency Syndrome by Beischel, Julie Marie, PhD from The University of Arizona, 2003, 125 pages http://wwwlib.umi.com/dissertations/fullcit/3089910
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The Role of Cytoskeletal Lim Protein Deficiency in the Development of Dilated Cardiomyopathy by Lorenzen-Schmidt, Ilka, PhD from University of California, San Diego, 2003, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3099547
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The Role of Lipid Abnormalities in the Development of Diabetic Cardiomyopathy by Rodrigues, Brian Baltzar; PhD from The University of British Columbia (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL50580
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. CLINICAL TRIALS AND CARDIOMYOPATHY Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning cardiomyopathy.
Recent Trials on Cardiomyopathy The following is a list of recent trials dedicated to cardiomyopathy.8 Further information on a trial is available at the Web site indicated. •
Evaluation of Patients with Known or Suspected Heart Disease Condition(s): Chest Pain; Coronary Cardiomyopathy; Syndrome X
Disease;
Heart
Disease;
Hypertrophic
Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: In this study researchers will admit and evaluate patients with known or suspected heart disease referred to the Cardiology Branch of the National Heart, Lung, and Blood Institute (NHLBI). Patients participating in this study will undergo a general medical evaluation, including blood tests, urine, examination, chest x-ray and electrocardiogram (EKG). In addition, patients may be asked to have an echocardiogram (ultrasound scan of the heart) and to perform an exercise stress test. These tests are designed to assess the types and causes of patient's heart diseases and to determine if they can participate in other, specific research studies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001313 •
Family Studies of Hypertrophic/Dilated Cardiomyopathy Condition(s): Hypertrophic Cardiomyopathy; Congestive Cardiomyopathy
8
These are listed at www.ClinicalTrials.gov.
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Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine blood cells of patients (and their relatives) with hypertrophic cardiomyopathy or dilated cardiomyopathy for genes that may cause or modify the disease. Cardiomyopathy causes thickening or stretching of the heart muscle that can cause chest pain, shortness of breath, palpitations, and fainting. Cardiomyopathy sometimes runs in families and is caused by an abnormal gene or genes. Patients diagnosed with hypertrophic cardiomyopathy or dilated cardiomyopathy, or both, may enroll in this study. Relatives of patients will also be studied. Participants will have a review of their medical history and a brief physical examination, including and electrocardiogram (EKG) and echocardiogram-an ultrasound test of the heart. A small blood sample will be obtained for DNA (genetic) study. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00045825 •
Randomized Trial of a Telephone Intervention in Heart Failure Patients Condition(s): Heart Failure, Congestive; Cardiomyopathy Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: In addition to medical treatment for heart failure (HF), a variety of non-pharmacological interventions have been demonstrated to benefit these patients. Some of these include systems for weight monitoring and medication reminders, exercise programs, and individually tailored evaluation and treatment plans with dieticians, social workers, psychologists, and nurse case managers. While many of these approaches have been shown to increase adherence to medication guidelines and result in decreased health care utilization, most rely heavily on a large team of specialized health care providers. It remains unknown whether or not an intervention with a lower intensity of specialized care using sophisticated automated computer tracking and Interactive Voice Response (IVR) techniques can impact the care of HF patients. The primary hypothesis of this study is that Heart Failure Telephone Intervention (HearT-I) will decrease hospitalizations and clinic visits in the veteran population with heart failure. The HearT-I intervention consists of three components: 1) computer-initiated medication refill and clinic appointment reminders; 2) IVR access to educational modules; and 3) weekly computer-initiated phone calls with a series of questions regarding weight and symptoms. Four hundred eighty-eight HF patients (NYHA class II-IV) will be randomized to HearT-I intervention vs. usual care. Upon enrollment, all patients will complete questionnaires assessing HF knowledge, behavior, self-efficacy, and perceptions of HF health care, and HF related Quality of Life (Kansas City Cardiomyopathy Questionnaire, KCCQ). Both groups also will receive a digital scale, educational materials, view an educational video about HF and perform a six-minute walk test. We will test the hypothesis that the HearT-I intervention will decrease health care utilization as measured by hospitalizations and unscheduled outpatient visits for HF over one year. Secondary endpoints include KCCQ score, patient satisfaction, adherence to medications, and general knowledge of heart failure and its management. Study Type: Interventional
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057057 •
The Role of Heart Stiff and Weak Atrium on Exercise Capacity in Patients with Hypertrophic Cardiomyopathy Condition(s): Cardiomyopathy, Hypertrophic Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine how heart stiffness and a weak atrium affect exercise capacity and symptoms in patients with hypertrophic cardiomyopathy (HCM). The atrium is the booster pumping chamber of the heart that helps the ventricle (main pumping chamber), to fill properly. HCM is an inherited disease in which the ventricle becomes thickened and, in some patients, stiff. The stiffness makes it difficult for the ventricle to fill and empty, causing breathing difficulty, fatigue, and reduced exercise capacity. Scar formation and a weakened atrium can cause the heart to stiffen. Information gained from this study may guide doctors in prescribing medicines to reduce scarring or improve atrial function. Patients 21 years of age and older with hypertrophic cardiomyopathy may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram (EKG), blood tests, Holter monitor, and echocardiogram. A Holter monitor is a device about the size of a Walkman that is connected to three wires that are attached to the chest. It is worn for 24 hours to provide continuous monitoring of heart rhythm. An echocardiogram uses a small probe that emits sound waves to produce images of the heart. The probe is moved across the chest and the reflection of the sound waves from the chambers of the heart produce images showing the heart's thickness and function. Participants will undergo the following tests and procedures over 3 days: -Physical examination and echocardiogram. -Intravenous cannula insertion: A plastic tube is inserted into an arm vein for collecting blood samples to measure substances that the heart and circulatory system release at rest and during exercise. -Impedance cardiography: A small current of electricity is passed across the chest and electrodes similar to those used for an EKG test are placed to measure blood flow in the area of the current. -Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein either in the arm, under the collarbone, or in the neck and advanced to the right atrium and ventricle. The catheter remains in place during the echocardiogram tilt and bicycle exercise tests (see below). -Echocardiogram tilt test: The patient lies flat on a table. After a few minutes, the table is tilted so that the patient's head is just above his or her feet for a short while, then is positioned flat again, and then tilted so the feet are just above the head. Echocardiographic measurements and blood samples are taken at intervals to examine heart function during changes in posture. -Echocardiogram bicycle stress test: The patient exercises for as long as possible on a bicycle-like machine while lying on his or her back. Echocardiographic measurements and blood samples are taken at intervals during the test. -Treadmill stress test: The patient runs for as long as possible on a treadmill that increases in difficulty. The patient wears a facemask or mouthpiece through which small amounts of gases are added in order to measure the ability of the heart and lung to increase their effectiveness with exercise. -Digoxin loading: Only patients who demonstrate limited exercise capacity and for whom digoxin is not a risk will undergo this procedure. A medicine that makes the heart contract more strongly, digoxin is used to treat certain heart abnormalities. Patients are given doses of either digoxin or placebo (a look-alike injection with no active ingredient) at 4-hour intervals
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over a 24-hour period and then repeat the tilt test and the bicycle and treadmill exercise tests Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00074880 •
Mapping Novel Disease Genes for Dilated Cardiomyopathy Condition(s): Cardiomyopathy, Congestive; Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To identify new dilated cardiomyopathy genes by genetic linkage and mutational analyses. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046618
•
Natural History and Results of Dual Chamber (DDD) Pacemaker Therapy of Children with Obstructive Hypertrophic Cardiomyopathy (HCM) Condition(s): Hypertrophic Cardiomyopathy Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Several studies have shown that specialized pacemaking devices (DDD pacing) can improve the symptoms associated with hypertrophic cardiomyopathy (HCM) in adults. In addition, studies have also shown that specialized pacemaking devices (DDD pacing) can improve conditions of HCM in children. However, growth of the body and organs, including the heart, is very rapid during childhood. Therefore the long-term effects of DDD pacing in children are unknown. The purpose of this study is to examine the growth rate and nutrition of children with HCM. Due to this heart condition and the restrictions that are often placed on the child's activity level, children with HCM may grow at a slower rat and may have a greater tendency to be overweight. Children participating in the study will have their growth rate and nutritional status measured before the study begins and throughout the course of the study. Findings in this research study will not directly benefit the patients participating in it. However, information gathered as a result of this study may lead to improvements in the management of children with HCM in the future. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001396
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Pediatric Cardiomyopathy Registry Condition(s): Cardiovascular Diseases; Heart Diseases; Myocardial Diseases
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Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To establish and maintain a national registry of children with different forms of cardiomyopathy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005391 •
A Comparison of Two Treatments' Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy Condition(s): Hypertrophic Cardiomyopathy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will compare two treatments: pacemaker implantation and percutaneous transluminal septal ablation (PTSA) for patients with hypertrophic cardiomyopathy (HCM), a condition in which the heart muscle thickens and obstructs the flow of blood out of the heart. The reduced blood flow can cause chest pain, shortness of breath, palpitations, tiredness, lightheadedness and fainting. Patients with HCM who cannot be helped by drug therapy may participate in the study. The standard treatment for such patients is septal myectomy, an operation in which the surgeon shaves the muscle obstructing the blood flow. Another treatment option is implantation of a type of pacemaker that causes the heart to contract in a certain way that reduces blood flow obstruction and improves symptoms. The pacemaker is implanted under local anesthesia and usually takes less than an hour. PTSA is an experimental treatment that may provide a third option. In PTSA, a thin tube (catheter) is inserted into the blood vessel that feeds the heart muscle causing the blood flow obstruction. A small amount of alcohol is injected through the catheter to destroy some of the muscle and relieve the obstruction. Candidates will have the following screening tests: chest X-ray, electrocardiogram, echocardiogram, exercise tests, exercise radionuclide angiography, exercise thallium scintigraphy, Holter monitoring, cardiac catheterization, electrophysiology study, and coronary angiography. Participants will be assigned to one of the two treatments groups: pacemaker implantation or PTSA. Patients in the PTSA group will also have magnetic resonance imaging scans at the start of the study, 3 to 7 days after PTSA, and at the end of the study, in order to observe changes in the heart's shape. All patients will fill out a questionnaire answering questions about their quality of life. Patients' progress will be followed with monthly phone calls. In addition, various tests, such as exercise tests and echocardiography, will be done during repeat visits at three and six months to measure treatment results. Patients will again complete qualityof-life questionnaires at both of those visits. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001894
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AIDS-Associated Cardiomyopathy Condition(s): Acquired Immunodeficiency Syndrome; Heart Diseases; Myocardial Diseases; HIV Infections Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To define the incidence and prevalence of AIDS-associated cardiomyopathy. Also, to conduct immunopathology and serologic studies in endomyocardial biopsies and autopsy tissues. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005227
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Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study Condition(s): Hypertrophic Cardiomyopathy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will test the feasibility of a modified procedure for treating obstructive hypertrophic cardiomyopathy (OHC). Patients with OHC have a thickening of the heart muscle that obstructs blood flow out of the heart, causing breathlessness, chest pain, palpitations, tiredness, lightheadedness, and fainting. The current treatment for OHC is a procedure called alcohol septal ablation (also percutaneous transluminal septal ablation, or PTSA), which involves injecting a small amount of alcohol into a tiny artery that supplies the part of muscle causing blood flow obstruction. The success of PTSA is limited, however, by problems of heart anatomy and the ability to find the appropriate artery to inject. Modifying the procedure by injecting the alcohol through the wall of the lower right chamber of the heart may improve its safety and effectiveness. The new technique requires positioning a catheter (a flexible tube) into the appropriate area of the heart. This study will test the ability to accurately guide the catheter to that area. Patients with OHC 18 years of age and older who are scheduled to have a cardiac catheterization may be eligible for this study. At the end of the catheterization procedure, participants will undergo intra-cardiac echocardiographic imaging. For this test, one of the catheters placed in the femoral artery (at the top of the leg) for cardiac catheterization will be substituted for a larger one. Through this catheter, a special catheter will be introduced and advanced to the heart to provide images. This pilot feasibility study does not involve injection of alcohol. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035386
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Analysis of Heart Muscle Function in Patients with Heart Disease and Normal Volunteers Condition(s): Cardiomyopathy, Hypertrophic; Coronary Disease; Healthy; Myocardial Ischemia; Syndrome X Study Status: This study is completed.
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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Myocardial ischemia is a heart condition in which not enough blood supply and oxygen reaches the heart muscle. Damage to the major blood vessels of the heart (coronary artery disease), minor blood vessels of the heart (microvascular heart disease), or damage to the heart muscle (hypertrophic cardiomyopathy) can cause myocardial ischemia. Any of theses three conditions can cause patients to experience chest pain and other symptoms as well as cause the heart to function improperly. In order to detect myocardial ischemia researchers can use tests to measure the movement of the walls of the heart. Walls receiving inadequate supplies of blood often move less and occasionally move in the opposite direction. Some of the tests may require patients to receive injections of radioactive tracers. The radioactive material acts to enhance 3 dimensional pictures of the heart and helps to identify areas of ischemia. The purpose of this study is to determine whether 3-dimensional imaging (tomography) with radioactive tracers can provide more important information about heart wall function than routine diagnostic tests. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001459 •
Chagas Disease as an Undiagnosed Type of Cardiomyopathy in the United States Condition(s): Heart Diseases; Myocardial Diseases; Chagas Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: A detailed review was made of data pertinent to the occurrence of chronic Chagas disease in the United States. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005455
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Cyclosporine A to Treat Hypertrophic Cardiomyopathy (HCM) Condition(s): Cardiomyopathy, Hypertrophic; Heart Hypertrophy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine the effectiveness of the drug cyclosporine in treating hypertrophic cardiomyopathy (HCM), a condition in which the heart muscle thickens. The thickened muscle can impair the heart's pumping action or decrease its blood supply, or both. Various symptoms, such as chest pain, shortness of breath, fatigue, and palpitations, may result. In animal studies, cyclosporine prevented heart muscle from thickening in mice that had been engineered to develop thick hearts. Patients with HCM 18 to 75 years old are screened for this study under protocol 98-H0102 and this protocol. Screening tests include blood tests, echocardiogram to measure heart thickness, Holter monitor to record heartbeats, treadmill exercise test, and various imaging tests including a thallium scan, radionuclide angiography, magnetic resonance imaging (MRI), and cardiac catheterization to examine heart function and blood supply. Patients admitted to the study will be randomly assigned to take either cyclosporine tablets or a placebo (a look-alike tablet with no active ingredient) twice a day for 6
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months. During a brief hospital stay at the start of the study, blood samples will be taken to measure cyclosporine levels. After discharge, heart rate and blood pressure will be checked and blood tests done during follow-up visits once a week for 2 weeks and then every two weeks until the end of the 6-month treatment period. At that time, patients will be hospitalized a second time for repeat tests to determine the effects of the drug on the heart condition. They include thallium scan, radionuclide angiogram, MRI, treadmill exercise test, cardiac catheterization, and echocardiogram. An echocardiogram and MRI will be repeated 1 year after the start of the study to evaluate long term effects of the drug, if any. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001965 •
Effect of Behavioral Management on Quality of Life in Heart Failure Condition(s): Heart Failure, Congestive; Cardiomyopathy, Dilated Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs Purpose - Excerpt: Nurses play an important role in helping patients to manage symptoms, adhere to treatment, and change behavior. There has been a lack of research regarding nonpharmacologic interventions with patients with heart failure and other chronic conditions. The primary objective of this 4-year study was to determine the effect of a nurse-led behavioral management intervention on health-related quality in patients with medically-managed heart failure. The secondary objective was to assess the impact of the behavioral management intervention on health care resource utilization. DESIGN: randomized controlled trial. SETTING: single site, VA San Diego Healthcare System. SAMPLE: Patients were enrolled in 11 cohorts a total of 116 outpatients were randomly assigned to one of two treatment groups to evaluate the clinical impact of the intervention. Group 1 received usual care for patients with heart failure (n=58). Group 2 was an augmented group receiving usual care plus participation in the 15-week (4-month) behavioral management program (n=58). Inclusion criteria were that the patient had a primary diagnosis of heart failure, a VA primary care provider, stable symptoms for at least one month and was able to walk. INTERVENTION: The behavioral management program augmented usual care and consisted of establishing specific goals with patients related to healthier diet, increased quality and amount of exercise, smoking cessation, and increased social and interpersonal activities. DEPENDENT VARIABLES/OUTCOME MEASURES: The five major dependent variables for this study were psychological symptom distress (Multiple Affect Adjective Check List - MAACL), physical functioning (SF-36 physical component summary score), mental functioning (SF-36 mental component summary score), exercise capability (6-Minute Walk), and general health perceptions (SF-36 general health scale score). Dependent variables were assessed at baseline, at the end of treatment (at 4 months), and then at 10 and 16 months. DATA ANALYSIS: Initial analyses included all subjects who were randomized to treatment and completed all data collection time points in a series of 2 by 4 ANOVAs with time as a repeated measure. Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00012870 •
Epidemiology of Idiopathic Dilated Cardiomyopathy (Washington, DC Dilated Cardiomyopathy Study) Condition(s): Cardiovascular Diseases; Heart Diseases; Myocardial Diseases; Asthma; Diabetes Mellitus; Hypertension Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To identify risk factors for idiopathic dilated cardiomyopathy and to examine prognostic factors over a follow-up period of two to three years. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005262
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Factors Contributing to Increased Left Ventricle Size in Patients with Abnormally Enlarged Hearts Condition(s): Hypertrophic Cardiomyopathy; Left Ventricular Hypertrophy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into the circulation. There is an inherited condition affecting the heart, passed on through genetics, hypertrophic cardiomyopathy (HCM). HCM causes the left ventricle to become abnormally enlarged (left ventricular hypertrophy LVH). Some patients with the abnormal genes that may cause HCM do not have the characteristic LVH. Approximately 20 - 40% of patients with the genetic abnormality (missense mutation of genes encoding for sarcomeric protein) actually have an enlarged left ventricle. Because of this, researchers believe there may be other factors, along with the genetic abnormality that contribute to the development of HCM. Researchers are interested in learning more about several factors they suspect may play a role in the development of HCM. Specifically, researchers plan to study levels of a hormone and the protein it attaches to, which may contribute to the development of an abnormally enlarged heart. Insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein (IGFBP) work together with growth hormone (GH) in the development and maturation of many organ systems. Previous studies have suggested that these hormones affect the development and function of the heart. Patients participating in this study will undergo a variety of tests including collection of blood samples, echocardiogram of the heart, treadmill exercise test, and continuous electrical monitoring of heart activity (Holter monitor). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001878
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Family Studies of Inherited Heart Disease Condition(s): Hypertrophic Cardiomyopathy
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Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Hypertrophic cardiomyopathy (HCM) is a genetically inherited heart disease. It causes thickening of heart muscle, especially the chamber responsible for pumping blood out of the heart, the left ventricle. Hypertrophic cardiomyopathy (HCM) is the most important cause of sudden death in apparently healthy young people. A genetic test called linkage analysis is used to locate genes causing inherited diseases like HCM. Linkage analysis requires large families to be evaluated clinically in order to identify the members with and without the disease. In this study researchers will collect samples of DNA from family members of patients with HCM. The diagnosis of the disease will be made by history and physical examination, electrocardiogram (12 lead ECG), and ultrasound of the heart (2-D echocardiogram). The ability of the researchers to locate the gene responsible for the disease improves with increases in the size of the family and members evaluated. In order to continue research on the genetic causes of heart disease, researchers intend on studying families with specific genetic mutations (beta-MHC) causing HCM. Researcher plan to also study families with HCM not linked to specific gene mutations (beta-MHC). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001225 •
Genetic Analysis of Familial Hypertrophic Cardiomyopathy Condition(s): Cardiovascular Diseases; Cardiomyopathy, Hypertrophic
Heart
Diseases;
Myocardial
Diseases;
Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To map the genetic defect responsible for familial hypertrophic cardiomyopathy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005251 •
Home Walking Exercise Training in Advanced Heart Failure Condition(s): Cardiomyopathy, Congestive Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: Heart failure (HF) is a major public health burden in the United States. Despite considerable advances in the diagnosis and management of HF, it remains one of the leading causes of morbidity and mortality. HF is a progressive cardiovascular syndrome characterized by a reduction in exercise capacity with distressing symptoms of exertional fatigue and dyspnea. Currently, much of HF therapy is aimed at increasing survival. Yet, for many patients prolonged survival may be less critical than improved functional status and quality of life.38,39 Hence, a nursing intervention designed to ameliorate symptoms, maximize functional status, and achieve
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a high level of well-being is clinically relevant. Investigators have suggested that either a cardiac rehabilitation program or a home bicycle exercise training program may improve peak oxygen consumption, symptom scores and reverse autonomic imbalance. Improvement of peak oxygen consumption may not necessarily translate into improve functional status and quality of life. A cardiac rehabilitation program or bicycle ergometer may be costly for patients to perform. Utilizing a 2-group pre-test-post-test experimental design, the specific aim is to compare functional status (FS), quality of life (QOL) and neurohormonal activation in 2 groups of advanced HF patients (control group vs. home walking exercise (HWE) group). Will a 12-week HWE program decrease sympathetic activity, increase FS, and/or improve QOL? Heart failure patients from WLA-VAMC who meets inclusion criteria (dilated cardiomyopathy for 3 months, LVEF < 40%, NYHA Class II-III, 25-80 years) and exclusion criteria (i.e. MI or recurrent angina in past 3 months, orthopedic impediments, severe COPD, stenotic valvular disease, ventricular tachyarrhythmias, etc) are considered. Sample size will be 55 in each group. Consented patients are stratified by age: younger (< 60 years) and older (> 60 years); then, randomized into either control or experimental group. Control group performs "limited physical activity" for 12weeks; whereas, experimental group performs a 12week HWE program. The 12- week HWE program is once a day, 5x a week and initiated at 10 minutes and progressively increases in duration and intensity up to 45 minutes. Pre- and post-study measures are sympathetic activation (norepinephrine (NE)), FS (peak VO2 via cardiopulmonary exercise test and a Heart Failure Functional Status Inventory), and QOL (Cardiac Quality of life Index by Ferrans and Powers, and the Dyspnea-Fatigue Rating Index). Between group differences over time for FS (VO2max, and HFFSI scores), QOL (C-QLI and Dyspnea-Fatigue Rating Index scores), neurohormonal activation (NE levels) will be evaluated by repeated measures multivariate analysis of variance. Significance will be set at alpha=.05. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012883 •
Idiopathic Dilated Cardiomyopathy Condition(s): Heart Diseases; Cardiomyopathy, Congestive Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the familial occurrence and pathogenesis of idiopathic dilated cardiomyopathy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005201
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Investigation into the Use of Ultrasound Technique in the Evaluation of Heart Disease Condition(s): Healthy; Hypertrophic Cardiomyopathy; Left Ventricular Hypertrophy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)
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Purpose - Excerpt: The human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into the circulation. Hypertrophic cardiomyopathy is a genetically inherited disease causing an abnormal thickening of heart muscle, especially the muscle making up the left ventricle. When the left ventricle becomes abnormally large, it is called left ventricular hypertrophy (LVH). Patients with HCM can be born with an enlarged left ventricle or they may develop the condition in childhood or adolescence, usually during the time when the body is rapidly growing. However, not all patients with the abnormal genes linked to HCM have the characteristic LVH. Currently, it is impossible to tell if a patient with the genes for HCM will develop LVH. A recently developed ultrasound tool called an integrated backscatter analysis (IBS), may allow researchers to determine those children who may later develop HCM and LVH. In order to test this, researchers plan to use IBS to study normal children with relatives diagnosed with HCM. This study will compare the results of IBS done on normal children with relatives diagnosed with HCM , normal children, and children with evidence enlarged heart muscle (HCM). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001632 •
Long Term Effects of Enalapril and Losartan on Genetic Heart Disease Condition(s): Hypertrophic Myocardial Ischemia
Cardiomyopathy;
Left
Ventricular
Hypertrophy;
Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into circulation. Hypertrophic cardiomyopathy (HCM) is a genetically inherited disease causing an abnormal thickening of the heart muscle, especially the muscle making up the left ventricle. When the left ventricle becomes abnormally large it is called left ventricular hypertrophy (LVH). This condition can cause symptoms of chest pain, shortness of breath, fatigue, and heart beat palpitations. This study is designed to compare the ability of two drugs (enalapril and losartan) to improve symptoms and heart function of patients diagnosed with hypertrophic cardiomyopathy (HCM). Researchers have decided to compare these drugs because each one has been used to treat patients with other diseases causing thickening of the heart muscle. In these other conditions, enalapril and losartan have improved symptoms, decreased the thickness of heart muscle, improved blood flow and supply to the heart muscle, and improved the pumping action of the heart muscle. In this study researchers will compare the effectiveness of enalapril and losartan when given separately and together to patients with hypertrophic cardiomyopathy (HCM). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001534 •
Long-Term Results of DDD Pacing in Obstructive Hypertrophic Cardiomyopathy Condition(s): Cardiomyopathy, Hypertrophic Study Status: This study is completed.
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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: DDD pacing improves symptoms and relieves LV outflow tract (LVOT) obstruction in most patients with hypertrophic cardiomyopathy (HCM). Notably, when pacing is temporarily discontinued, the beneficial effects of pacing are evident in sinus rhythm. The long term results of this novel therapy are, however, uncertain. We propose (1) to record the hemodynamic changes following >4 years of pacing; and (2) to determine whether DDD pacing continues to be necessary in patients who have had a substantial relief of their LVOT obstruction. Patients who have had >50% reduction in LVOT pressure gradients will be randomized to two pacing modalities: DDD at 70 beats per minute and AAI pacing at 70 beats per minute (DDD switched off), and reevaluated after a six-month period. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001530 •
Mortality Surveillance of MRFIT Screenees Condition(s): Cardiovascular Diseases; Heart Diseases; Cerebrovascular Accident; Coronary Disease; Hypertension; Cardiomyopathy, Congestive Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To ascertain the sixteen year mortality status of the 361,662 middleaged men screened in 1973-1975 for the Multiple Risk Factor Intervention Trial (MRFIT). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005156
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Pirfenidone to Treat Hypertrophic Cardiomyopathy Condition(s): Hypertrophic Cardiomyopathy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine the effectiveness of the drug pirfenidone (Deskar) in improving heart function in patients with hypertrophic cardiomyopathy (HCM). Stiffening of the heart muscle in patients with HCM impairs the heart's ability to relax and thus fill and empty properly. This can lead to heart failure, breathlessness and excessive fatigue. The heart's inability to relax may be due to scarring, or fibrosis, in the muscle wall. This study will test whether pirfenidone can reduce fibrosis, improve heart relaxation and reduce abnormal heart rhythms. Men and women 20 to 75 years old with HCM may be eligible for this study. Participants will undergo a physical examination, blood tests, and other tests and procedures, described below, to assess heart function. When the tests are completed, patients will be randomly assigned to one of two treatment groups. One group will take a pirfenidone capsule and the other will take a placebo (a look-alike pill with no active ingredient) twice a day with meals for 6 months. For the pirfenidone group, the dose of drug will be increased gradually from 400 to 800 milligrams. At the end of 6 months, all patients will repeat the physical examination and heart tests that were done before starting medication. These include: -Electrocardiogram (ECG) - electrodes are attached to the heart to record the heart's electrical activity,
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providing information on the heartbeat. -Echocardiogram - a probe held against the chest wall uses sound waves to produce images of the heart, providing information on the function of the heart chambers. -24-hour Holter monitor - a 24-hour recording of the electrical activity of the heart monitors for abnormal heartbeats or conduction abnormalities. -Magnetic resonance imaging (MRI) - Radiowaves and a strong magnetic field are used to produce images of the heart, providing information on the thickness and movement of the heart muscle. -Radionuclide angiogram - a radioactive tracer is injected into a vein and a special camera is used to scan the heart, providing information on the beating motion of the heart. Scans are obtained at rest and after exercise. -Cardiac (heart) catheterization - a catheter (thin plastic tube) is inserted into a blood vessel in the groin and advanced to the heart to record pressures and take pictures inside the heart. Electrophysiology study - a catheter is inserted into a blood vessel in the groin and advanced to the heart to record electrical activity, providing information on abnormal heart rhythms. This procedure is done at the time of the heart catheterization. -Cardiac biopsy - a catheter is inserted into a blood vessel in the groin and advanced to the heart to remove a small sample of heart muscle for microscopic examination. This procedure is done at the end of the heart catheterization. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011076 •
Screening for Inherited Heart Disease Condition(s): Heart Disease; Hypertrophic Cardiomyopathy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Genetically inherited heart diseases like hypertrophic cardiomyopathy (HCM) are conditions affecting the heart passed on to family members by abnormalities in genetic information. These conditions are responsible for many heart related deaths and illnesses. Presently, there are several research studies being conducted in order to improve the understanding of disease processes and symptoms associated with genetically inherited heart diseases. This study is designed to determine the eligibility of patients diagnosed with or suspected to have inherited heart disease to participate in these research studies. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001746
•
Study of Blood Flow in Heart Muscle Condition(s): Coronary Disease; Healthy; Hypertrophic Cardiomyopathy; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Blood flows to areas of the heart providing oxygen and fuel to the pumping muscle. Occasionally the arteries providing the fuel can become blocked. This occurs in coronary artery disease. Magnetic resonance imaging (MRI) can be used to
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evaluate the blood flow to different areas of the heart muscle. In this study magnetic resonance imaging will be compared to other diagnostic tests (radionucleotide perfusion studies) capable of measuring blood flow to heart muscle. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001631 •
Studying the Effectiveness of Pacemaker Therapy in Children who Have Thickened Heart Muscle Condition(s): Hypertrophic Cardiomyopathy Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: A heart condition called hypertrophic cardiomyopathy (HCM) causes abnormal thickening of the heart muscle, which obstructs the flow of blood out of the heart. The thickened muscle and the obstruction of blood flow are believed to cause chest discomfort, breathlessness, fainting, and a sensation of heart pounding. Treatment options for children with HCM include medicine, heart operation, and cardiac transplantation. However, there is no evidence that medicine prevents further thickening of heart muscle; operations carry the risk of death; and donor hearts are not always available. Several studies have shown that pacemaker treatment reduces the obstruction and improves heart complaints in patients with HCM. This study investigates further the efficacy of pacemaker treatment in children. Patients will have exercise tests after treatment with beta blocker and verapamil and will be eligible for the study if heart complaints or reduced exercise performance continue. A pacemaker that treats slow heart rhythms will be inserted. The patient will be sedated and local anesthesia will be administered to numb the area. The procedure takes about an hour. The study will last two years. Patients will be placed on one of two pacemaker programs for the first year and another the second year. At 3- and 6-month follow-up visits, a pacemaker check and echocardiogram will be performed. After 1 year, patients will be admitted to NIH for 2 to 3 days for exercise tests, echocardiogram, and cardiac catheterization. Also, the pacemaker will be changed to the second program. At 15- and 18-month follow-up visits, a pacemaker check and echocardiogram will be performed. After 2 years, patients will again be admitted for 2 to 3 days for exercise tests, echocardiogram, and cardiac catheterization. A pregnancy test will be given to females of child-bearing age before each cardiac catheterization and electrophysiology study. At the end of the study, the pacemaker will be set to the program that worked better. Risks of pacemaker insertion include lung collapse, infection, blood vessel damage, bleeding, heart attack, and death. Risks of cardiac catheterization include infection, bleeding, blood clots, abnormal heart rhythms, perforation of the heart, need for surgery, and death. However, the safety record for both these procedures at NIH has been excellent. The radiation exposure exceeds the NIH radiation guidelines for children, but this exposure in adults has not been associated with any definite adverse effects. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001960
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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “cardiomyopathy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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•
For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON CARDIOMYOPATHY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “cardiomyopathy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cardiomyopathy, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Cardiomyopathy By performing a patent search focusing on cardiomyopathy, 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. 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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Cardiomyopathy
The following is an example of the type of information that you can expect to obtain from a patent search on cardiomyopathy: •
Actin mutations in dilated cardiomyopathy, a heritable form of heart failure Inventor(s): Keating; Mark T. (Salt Lake City, UT), Olson; Thomas M. (Salt Lake City, UT) Assignee(s): University of Utah Research Foundation (salt Lake City, Ut) Patent Number: 6,063,576 Date filed: June 29, 1998 Abstract: Two mutations in the human cardiac actin gene are disclosed which have been associated with idiopathic dilated cardiomyopathy (IDC) in two families. These mutations cosegregate with IDC in the two families. Both mutations affect universally conserved amino acids in domains of actin that attach to Z bands and intercalated discs. Analysis of the cardiac actin gene can be used to determine the presence in a patient of IDC resulting from mutations in this gene. Such analysis is useful in the diagnosis and prognosis of the disease in patients with mutations in this gene. Excerpt(s): Heart failure is a major medical problem that affects 700 thousand individuals per year in the United States and accounts for annual costs of 10 to 40 billion dollars (Abraham and Bristow, 1997). Heart failure is the primary manifestation of dilated cardiomyopathy, a group of disorders characterized by cardiac dilation and pump dysfunction. Half of patients with dilated cardiomyopathy are diagnosed with idiopathic dilated cardiomyopathy (IDC), isolated heart failure of unknown etiology (affecting 5 to 8 in 100,000 individuals) (Manolio et al., 1992; Kasper et al., 1994). Cardiac transplantation is the only definitive treatment for end-stage disease. The present invention is directed to ACTC and its gene products, mutations in the gene, the mutated gene, probes for the wild-type and mutated gene, and to a process for the diagnosis and prevention of idiopathic dilated cardiomyopathy. The instant work shows that some families with idiopathic dilated cardiomyopathy have mutations in ACTC. Idiopathic dilated cardiomyopathy is diagnosed in accordance with the present invention by analyzing the DNA sequence of the ACTC gene of an individual to be tested and comparing the respective DNA sequence to the known DNA sequence of normal ACTC. Alternatively, the ACTC gene of an individual to be tested can be screened for mutations which cause idiopathic dilated cardiomyopathy. The publications and other materials used herein to illuminate the background of the invention or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the appended List of References. Web site: http://www.delphion.com/details?pn=US06063576__
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Adeno associated virus vectors for the treatment of a cardiomyopathy Inventor(s): Byrne; Barry J. (Baltimore, MD), Kessler; Paul D. (Baltimore, MD), Kurtzman; Gary J. (Menlo Park, CA), Podsakoff; Gregory M. (Fullerton, CA) Assignee(s): Avigen, Inc. (alameda, Ca), Johns Hopkins University (baltimore, Md) Patent Number: 6,610,290 Date filed: October 1, 2001
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Abstract: The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of the delivered gene and for in vivo secretion of the therapeutic protein from transduced muscle cells such that systemic delivery is achieved. Excerpt(s): The present invention relates generally to DNA delivery methods. More particularly, the invention relates to the use of recombinant adeno-associated virus (AAV) virions for delivery of a selected gene to muscle cells and tissue. The method provides for sustained, high-level expression of the delivered gene. Gene delivery is a promising method for the treatment of acquired and inherited diseases. Muscle tissue is an appealing gene delivery target because it is readily accessible, well-differentiated and nondividing. Barr and Leiden (1991) Science 254:1507-1509. These properties are important in the selection of appropriate delivery strategies to achieve maximal gene transfer. Several experimenters have demonstrated the ability to deliver genes to muscle cells with the subsequent systemic circulation of proteins encoded by the delivered genes. See, e.g., Wolff et al. (1990) Science 247:1465-1468; Acsadi et al. (1991) Nature 352:815-818; Barr and Leiden (1991) Science 254:1507-1509; Dhawan et al. (1991) Science 254:1509-1512; Wolff et al. (1992) Human Mol. Genet. 1:363-369; Eyal et al. (1993) Proc. Nat. Acad. Sci. USA 90:4523-4527; Davis et al. (1993) Hum. Gene Therapy 4:151-159. Web site: http://www.delphion.com/details?pn=US06610290__ •
Agent for gene therapy of dilated cardiomyopathy Inventor(s): Toyo-Oka; Teruhiko (23-3, Kamiogi 3-chome, Suginami-ku, Tokyo 167-0043, JP) Assignee(s): None Reported Patent Number: 6,589,523 Date filed: January 25, 2001 Abstract: According to the present invention, there is provided a gene expression vector which is obtained by inserting a gene encoding sarcoglycan into an adeno-associated virus (AAV) vector. By administering the gene expression vector of the present invention to a living body in vivo, a sarcoglycan can be continuously expressed in the living body, so that the restoration of.alpha.-,.beta.-,.gamma.- and.delta.-sarcoglycan components can be accompanied and the heart function of the patient of dilated cardiomyopathy can be improved. Excerpt(s): The present invention relates to an agent for gene therapy of dilated cardiomyopathy, more particularly, a gene expression vector which is obtained by inserting a gene encoding a sarcoglycan into an adeno-associated virus vector. Cardiomyopathy is one of the heart diseases which shows contraction dysfunction and electrophysiological dysfunction as symptoms, and includes a group of heart diseases which lead to a sever heart failure and a sudden death. Cardiomyopathy is classified into dilated cardiomyopathy and hypertrophied cardiomyopathy, and the study for revealing the causes of each cardiomyopathy has been made. In the case of dilated cardiomyopathy (DCM), in spite of progress in the therapy, the prognosis of the patients is still poor and cardiac transplantation is necessary in the deteriorated cases (V.
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V. Michels, et al., New Engl.J.Med. 326, 77 (1992); E. K. Kasper, et al., J.Am.Coll.Cardiol. 23, 586 (1994); M. Packer, et al., New Engl.J.Med. 334, 1349 (1996); M. Packer, et al. New Engl.J.Med. 335,1107 (1996); R. M. Graham, W. A. Owens, N.Engl.J.Med. 341, 1759 (1999)). Therefore, it is necessary to develop a novel method for therapy which can improve the patient's mortality and morbidity. Animal model is useful for developing such a novel method for therapy. Gene transfer will be promising for the therapy of some type of DCM which is caused by the gene deletion. It has been demonstrated that the deletion of.delta.-sarcoglycan (.delta.-SG) gene is the cause of DCM in hamsters (A. Sakamoto, et al., Proc.Natl.Sci.Acad.U.S.A. 94, 13873 (1997); V. Nigro, et al., Hum.Mol.Genet. 6, 601 (1997)). Also, it has been found that the breakpoint of.delta.-SG gene in TO-2 hamster which is a model animal of DCM is present in the first intron, and large region including its promoter and the first exon is deleted in TO-2 hamster (A. Sakamoto, et al., Proc.Natl.Sci.Acad.U.S.A. 94, 13873 (1997)). Furthermore, dystrophinassociated glycoprotein complex (DAGC) links intracellular contractile machinery with extracellular matrix (G. F. Cox, L. M. Kunkel, Curr.Opin.Cardiol. 12, 329 (1997); K. H. Holt, et al., Mol. Cell 1, 841 (1998); M. D. Henry, K. P. Campbell, Curr.Opin.Cell Biol. 11, 602 (1999)). Web site: http://www.delphion.com/details?pn=US06589523__ •
Aldose reductase inhibition in preventing or reversing diabetic cardiomyopathy Inventor(s): Johnson; Brian F. (East Lyme, CT) Assignee(s): Pfizer Inc. (new York, Ny) Patent Number: 5,990,111 Date filed: May 1, 1998 Abstract: This invention relates to the use of aldose reductase inhibitors in the treatment, prevention or reversal of diabetic cardiomyopathy in a human subject. Excerpt(s): This invention relates to the use of aldose reductase inhibitors in the treatment or reversal of diabetic cardiomyopathy in a human subject. Of all identified diabetic sequelae, perhaps the most physiologically deleterious are those complications involving the cardiovascular system. These may, for example, involve the blood or nervous supply to the heart or the heart muscle (myocardium) directly. An associated disease state related to myocardial abnormalities is diabetic cardiomyopathy, an affliction in which subjects afflicted therewith manifest such symptomes as, inter alia, an overall reduction in cardiac performance, reduced ventricular compliance as characterized by slowed, incomplete cardiac filling (diastolic dysfunction), an increased incidence of congestive heart failure and a markedly enhanced potential for death during episodes of myocardial infarction. Moreover, secondary indicators such as the development of interstitial and myocellular tissue abnormalities (including interstitial, perivascular and focal scar-like connective tissue accumulations) may be present in addition to microangiopathy (including thickening of the capillary basement membrane, pericapillary edema and capillary microaneurysms). These characteristic abnormalities define the syndrome of diabetic cardiomyopathy. Detailed discussions of this condition may be found, for example, in F. S. Fein, et. al., "Diabetic Cardiomyopathy", Cardiovascular Drugs and Therapy, Vol. 8, pp. 65-73, 1994, and D. S. H. Bell, "Diabetic Cardiomyopathy", Diabetes Care, Vol. 18, pp. 708-714, 1995 and pertinent references cited therein. Aldose reductase inhibitors constitute a class of compounds which have become well known for their utility in the treatment of certain diabetic complications such as ocular cataract formation and diabetic neuropathy and nephropathy. Such
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compounds are well known to those skilled in the art and may be identified by standard biological methodology. Web site: http://www.delphion.com/details?pn=US05990111__ •
Combination of aldose reductase inhibitors and selective serotonin reuptake inhibitors for the treatment of diabetic complications Inventor(s): Mylari; Banavara L. (Waterford, CT) Assignee(s): Pfizer, Inc. (new York, Ny) Patent Number: 6,380,200 Date filed: December 1, 2000 Abstract: This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and selective serotonin reuptake inhibitor (SSRI), a prodrug thereof or a pharmaceutically acceptable salt of said SSRI or said prodrug. This invention further relates to methods of using those pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, myocardial infarction, cataracts and diabetic cardiomyopathy. Excerpt(s): This invention relates to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective serotonin reuptake inhibitor (SSRI), a prodrug thereof or a pharmaceutically acceptable salt of said SSRI or said prodrug. This invention further relates to methods of using such pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, myocardial infarction, cataracts and diabetic cardiomyopathy. Aldose reductase inhibitors function by inhibiting the activity of the enzyme aldose reductase, which is primarily responsible for regulating the reduction of aldoses, such as glucose and galactose, to the corresponding polyols, such as sorbitol and galactitol, in humans and other animals. In this way, unwanted accumulations of galactitol in the lens of galactosemic subjects and of sorbitol in the lens, peripheral nervous cord and kidneys of various diabetic subjects are prevented or reduced. Accordingly, aldose reductase inhibitors are of therapeutic value for controlling certain diabetic complications, e.g., diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, myocardial infarction, cataracts and diabetic retinopathy. Selective serotonin reuptake inhibitors function by inhibiting the reuptake of serotonin by afferent neurons. Web site: http://www.delphion.com/details?pn=US06380200__
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Combination of gaba agonists and sorbitol dehydrogenase inhibitors Inventor(s): Mylari; Banavara L. (Waterford, CT) Assignee(s): Pfizer Inc (new York, Ny) Patent Number: 6,544,998 Date filed: November 29, 2001
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Abstract: This invention relates to pharmaceutical compositions comprising combinations of a GABA agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and a SDI, a prodrug thereof or a pharmaceutically acceptable salt of said SDI or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. Excerpt(s): This invention relates to pharmaceutical combinations of a.gamma.aminobutyric acid (GABA) agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and a sorbitol dehydrogenase inhibitor (SDI), a prodrug thereof or a pharmaceutically acceptable salt of said SDI or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from diabetic complications such as, inter alia, diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. This invention also relates to additive and synergistic combinations of a GABA agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and a SDI, a prodrug thereof or a pharmaceutically acceptable salt of said SDI or said prodrug, whereby those additive and synergistic combinations are useful in treating mammals, including humans, suffering from diabetic complications such as, inter alia, diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. By gating negative chloride (Cl.sup.31) ions into the interior of cells, GABA inhibits the presynaptic release of neurotransmitter due to a positive voltage polarization pulse. Such inhibition is extremely common: GABA receptors can be found in 60-80% of central nervous system neurons. Subtypes of GABA receptors can be activated by the mushroom toxin muscimol (at GABA.sub.A) as well as the antispasmodic amino acid baclofen (GABA.sub.B). These compounds directly mimic the action of GABA at the receptor. Allosteric facilitation of GABA receptors occurs at several distinct sites; the compounds which bind there are used as sedatives and anxiolytics. Progabide is a prodrug which decomposes to GABA after crossing the blood/brain barrier into the central nervous system. Vigabatrin (gamma-vinyl-GABA) promotes binding of GABA by inhibiting GABA-aminotransferase (GABA-T), the enzyme responsible for degrading GABA in the synapse. S. Ao et al., Metabolism, 40, 7787 (1991) have shown that significant functional improvement in the nerves of diabetic rats (based on nerve conduction velocity) occurs when nerve fructose levels are pharmacologically lowered, and that such improvement correlates more closely with the lowering of nerve fructose than the lowering of nerve sorbitol. Similar results were reported by N. E. Cameron and M. A. Cotter, Diabetic Medicine, 8, Suppl. 1, 35A-36A (1991). In both of these cases, lowering of nerve fructose was achieved using relatively high does of aldose reductase inhibitors, which inhibit the formation of sorbitol, a precursor of fructose, from glucose via the enzyme aldose reductase. Web site: http://www.delphion.com/details?pn=US06544998__
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Dual chamber pacing system having time-adaptive AV delay Inventor(s): Heynen; Henri G. M. (Geleen, NL), Struble; Chester (Eijsden, NL) Assignee(s): Medtronic, Inc. (minneapolis, Mn) Patent Number: 6,507,756 Date filed: April 3, 2000 Abstract: Rate responsive pacing systems that employ a time-dependent AV delay in the pacing hearts in Congestive Heart Failure (CHF) with Dilated Cardiomyopathy (DCM) (a CHF/DCM heart) during a post-implant Time-Adaptive period are disclosed. A starting or initial AV delay is set to an intrinsic AV delay time interval exhibited by the patient's heart at the time of implant. A chronic AV delay is then set to a therapeutic AV delay time interval that is shorter than the intrinsic AV delay time interval and alleviates symptoms of the CHF/DCM heart. A Time-Adaptive AV delay (TA-AV delay) is employed during a post-implant Time-Adaptive period that gradually changes the initial AV delay to the chronic AV delay at the end of the post-implant Time-Adaptive period. Excerpt(s): The present invention relates to dual chamber pacing systems, including rate responsive pacing systems, and more particularly to the employment of a timedependent AV delay for pacing hearts in Congestive Heart Failure (CHF) with Dilated Cardiomyopathy (DCM). Dual chamber pacing systems operating in the multiprogrammable, DDD and DDDR pacing modes have been widely adopted in implantable dual chamber pacemakers and certain implantable cardioverter/defibrillators (ICDs) for providing atrial and ventricular (AV) synchronized pacing on demand. A DDD pacemaker implantable pulse generator (IPG) includes an atrial sense amplifier to detect atrial depolarizations or P-waves and generate an atrial sense event (A-EVENT) signal, a ventricular sense amplifier to detect ventricular depolarizations or R-waves and generate a ventricular sense event (VEVENT) signal, atrial and ventricular pacing pulse generators providing atrial and ventricular pacing (A-PACE and V-PACE) pulses, respectively, and an operating system governing pacing and sensing functions. If the atria fail to spontaneously beat within a pre-defined time interval (atrial escape interval), the pacemaker supplies an A-PACE pulse to the atria through an appropriate lead system. The IPG supplies a V-PACE pulse to the ventricles through an appropriate lead system at the time-out of an AV delay timed from a preceding A-EVENT or generation of an A-PACE pulse unless a nonrefractory V-EVENT is generated in response to an R-wave during the AV delay. Such AV synchronous pacemakers which perform this function have the capability of tracking the patient's natural sinus rhythm and preserving the hemodynamic contribution of the atrial contraction over a wide range of heart rates. The rate-adaptive DDDR pacing mode functions in the above-described manner but additionally provides rate modulation of a pacing escape interval between a programmable lower rate and an upper rate limit (URL) as a function of a physiologic signal or rate control parameter (RCP) developed by one or more physiologic sensors and related to the need for cardiac output. In the DDDR pacing mode, reliance on the intrinsic atrial heart rate is preferred if it is appropriately between the URL and the programmed lower rate. At times when the intrinsic atrial rate is inappropriately high, a variety of "mode switching" schemes for effecting switching between tracking modes and non-tracking modes (and a variety of transitional modes) based on the relationship between the atrial rate and the sensor derived pacing rate have been proposed as exemplified by commonly assigned U.S. Pat. No. 5,144,949, incorporated herein by reference in its entirety.
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Web site: http://www.delphion.com/details?pn=US06507756__ •
Effects of IFN-.gamma. on cardiac hypertrophy Inventor(s): Jin; Hongkui (San Bruno, CA), Lu; Hsienwie (Needham, MA), Paoni; Nicholas F. (Belmont, CA), Yang; Renhui (San Bruno, CA) Assignee(s): Genentech, Inc. (south San Francisco, Ca) Patent Number: 6,187,304 Date filed: March 19, 1999 Abstract: The invention concerns the treatment of cardiac hypertrophy by interferongamma (IFN-.gamma.). Cardiac hypertrophy may result from a variety of diverse pathologic conditions, including myocardial infarction, hypertension, hypertrophic cardiomyopathy, and valvular regurgitation. The treatment extends to all stages of the progression of cardiac hypertrophy, with or without structural damage of the heart muscle, regardless of the underlying cardiac disorder. Excerpt(s): The present invention relates generally to the effects of IFN-.gamma. on cardiac hypertrophy. More particularly, the invention concerns the use of IFN-.gamma. for the prevention and treatment of cardiac hypertrophy and associated pathological conditions. Interferons are relatively small, single-chain glycoproteins released by cells invaded by viruses or certain other substances. Interferons are presently grouped into three major classes, designated leukocyte interferon (interferon-alpha,.alpha.-interferon, IFN-.alpha.), fibroblast interferon (interferon-beta,.beta.-interferon, IFN-.beta.), and immune interferon-gamma,.gamma.-interferon, IFN-.gamma.). In response to viral infection, lymphocytes synthesize primarily.alpha.-interferon (along with a lesser amount of a distinct interferon species, commonly referred to as omega interferon), while infection of fibroblasts usually induces.beta.-interferon.alpha.- and.beta.interferons share about 20-30 percent amino acid sequence homology. The gene for human IFN-.beta. lacks introns, and encodes a protein possessing 29% amino acid sequence identity with human IFN-.alpha.I, suggesting that IFN-.alpha. and IFN-.beta. genes have evolved from a common ancestor (Taniguchi et al., Nature 285, 547-549 [1980]). By contrast, IFN-.gamma. is not induced by viral infection, but rather, is synthesized by lymphocytes in response to mitogens, and is scarcely related to the other two types of interferons in amino acid sequence. Interferons-.alpha. and -.beta. are known to induce MHC Class I antigens, while IFN-.gamma. induces MHC Class II antigen expression, and also increases the efficiency with which target cells present viral peptide in association with MHC Class I molecules for recognition by cytotoxic T cells. Interferon-.gamma., along with other cytokines, has been implicated as an inducer of inducible nitric oxide (iNOS) which, in turn, has been described as an important mediator of the inflammatory mechanism underlying heart failure, of the cardiac response to sepsis or allograft rejection, as well as of the progression of dilated cardiomyopathies of diverse etiologies. Ungureanu-Longrois et al., Circ. Res. 77, 494502 (1995); Pinsky et al., J. Clin. Invest. 95, 677-685 (1995); Singh et al., J. Biol. Chem. 270, 28471-8 (1995); Birks and Yacoub, Coronary Artery Disease 8, 389-402 (1997); Hattori et al., J. Mol. Cell. Cardiol. 29, 1585-92 (1997). Indeed, IFN-.gamma. has been reported to be the most potent single cytokine with regard to myocyte iNOS induction (Watkins et al., J. Mol. & Cell. Cardiol. 27, 2015-29 [1995]). Web site: http://www.delphion.com/details?pn=US06187304__
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Inhibitors of UDP-G1cNAc:Ga1.beta.1-3Ga1NAc.alpha.R.beta.1-6 Nacetylglucosaminyltransferase (core 2 G1cNAc-T) and use of the inhibitors to prevent or treat cardiomyopathy associated with diabetes Inventor(s): Dennis; James W. (c/o Mount Sinai Hospital, Toronto, Ontario, CA), King; George L. (101 Centre St., Dover, MA 02030), Koya; Daisuke (30 Matsunoki-cho, Shimogamo, Sakyo-Ku, Kyoto 606, JP), Nishio; Yoshihiko (9-12-601 Ichiriyama, Ohtsu, Shiga 520-21, JP), Warren; Charles E. (c/o Mount Sinai Hospital, Toronto, Ontario, CA) Assignee(s): None Reported Patent Number: 6,131,578 Date filed: October 2, 1997 Abstract: Cardiomyopathy associated with diabetes and hyperglycemia can be treated by administering to a subject suffering from this condition a substance that inhibits UDP-GlcNAc:Gal.beta.1-3GalNAc.alpha.R.beta.1-6-N-acetylglucosaminyl transferase (core 2 GlcNAc-T) activity. Excerpt(s): The invention relates to methods for preventing or treating cardiomyopathy associated with diabetes mellitus and hyperglycemia by inhibiting UDPGlcNAc:Gal.beta.1-3GalNAc.alpha.R.beta.1-6 N-acetylglucosaminyltransferase (core 2 GlcNAc-T); methods for screening for substances that affect cardiomyopathy associated with diabetes mellitus and hyperglycemia; and methods and pharmaceutical compositions containing the substances for preventing or treating cardiomyopathy associated with diabetes mellitus and hyperglycemia. Cardiovascular diseases are the major cause of morbidity and mortality in diabetic patients, involving cardiac tissues as well as large vessels in the brain, heart, and lower extremities (1). In the heart, the majority of the cardiac failure is probably due to atherosclerotic processes in the coronary vessels, but multiple studies have documented that a sizeable number of diabetic patients suffer from congestive heart failure without significant coronary disease (2, 3). In addition, type I diabetic patients with <5 yr of disease have been reported to have abnormal cardiac function in the absence of significant coronary vessel disease (4). These clinical findings are supported further by animal studies documenting biochemical and functional changes in the cardiac tissue shortly after induction of diabetes (5-8). From these results, it has been postulated that diabetes mellitus and its metabolic sequelae can induce a specific form of cardiomyopathy (8, 9). As with other chronic complications of diabetes, the cardio-vascular changes once established are difficult to reverse, both in clinical and experimental settings (10-12). Most cardiovascular abnormalities are metabolically induced with a great deal of interest directed towards identifying alterations in gene expression induced by diabetes or hyperglycemia in the vasculature. Since thickening of basement membrane is a classical finding in diabetes microvasculature (10), many of the studies concerning glucoseregulated genes have primarily focused on changes in the basement matrix components using cultured vascular cells (13, 14). Web site: http://www.delphion.com/details?pn=US06131578__
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Method and apparatus for the early detection of tissue pathology using wavelet transformation Inventor(s): Kerut, Sr.; Edmund Kenneth (8113 Ferrara Dr., Harahan, LA 70123) Assignee(s): None Reported Patent Number: 6,415,046 Date filed: October 7, 1999 Abstract: A method and apparatus for the early detection of tissue pathology using wavelet decomposition, such as Cardiomyopathy, for the early detection and diagnosis of disease using multi-dimensional non-invasive imaging techniques. The apparatus for early detection of tissue pathology includes a tissue texture quantifier apparatus having a wavelet decomposer for decomposing a region-of-interest (ROI) of a digitized image of anatomical tissue into vertical, horizontal and diagonal detail coefficients and a tissue pathology evaluator having a standard reference model. The tissue texture quantifier further includes a wavelet calculator to calculate the energy content for each of the vertical detail coefficient, the horizontal detail coefficient and the diagonal detail coefficient. Moreover, the tissue texture quantifier includes a summer for summing the energy content of the vertical detail coefficient, the horizontal detail coefficient and the diagonal detail coefficient and a normalizer for normalizing all energy content and the summed energy content. Excerpt(s): The present invention relates to methodologies for detecting tissue pathology, more particularly, to a method and apparatus for the early detection of tissue pathology using a wavelet decomposition method on tissue data obtained by using a multi-dimensional non-invasive imaging technique. Such method and apparatus provides a tool for physicians and researchers to diagnose and thus treat early stages of diseases or other disorders affecting suspect tissue to minimize irreversible tissue or other pathological damage caused by such disease. Detection of diseased tissue by other than histological or biochemical means is a challenge for non-invasive imaging techniques. Pathologies of organ, muscle and tissue, such as various forms of cardiomyopathy, represent a group of diseases in which a non-invasive imaging technique to distinguish normal from abnormal tissue would be of particular importance. Texture analysis of organs, muscles or tissue, such as myocardium, is an approach to tissue characterization based on the spatial distribution of amplitude signals within a region-of-interest (ROI). While I use ultrasound and myocardium as the tissue of interest to describe how to make and use my invention, the invention can be used for images obtained by other multi-dimensional non-invasive imaging techniques, and to study other tissues, such as skeletal muscle, liver, pancreas, kidneys, and arterial wall linings. My invention is especially suitable when only a small ROI is available for analysis, such as a 16.times.16 ROI, as it has been stated by others that statistical methods are less reliable for small ROI's as noise within the signal has a significant effect. However, my invention is also suitable for large ROI'S and, I speculate, is a better detector than statistical methods. The characterization of myocardial tissue itself by ultrasound was attempted in 1957 where excised human hearts were used to distinguish infarcted from normal myocardium. Web site: http://www.delphion.com/details?pn=US06415046__
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Method for testing cardiac myocarditis or cardiomyopathy Inventor(s): Matsumori; Akira (Osaka, JP) Assignee(s): Toray Industries, Inc. (jp) Patent Number: 6,214,535 Date filed: April 16, 1997 Abstract: The present invention relates to a method for the treatment of cardiac disease resulting from a viral infection of the cardiac tissue with human hepatitis C virus or EMC virus comprising administering an antiviral agent to a subject. The antiviral agent is useful in the treatment of myocarditis and cardiomyopathy. Excerpt(s): The present invention relates to a therapeutic agent for a cardiac disease in which the cardiac muscle tissue is infected with human hepatitis C virus and a method for testing a cardiac disease. Myocarditis is a disease caused by infection, allergy, poisoning or the like which will lead to inflammatory myocardial disorders and most of myocarditis is believed to be viral. As causative viruses, a number of enteroviruses are considered. In particular, Coxsackie B virus is believed to cause viral myocarditis most frequently. However, as viruses associated with cardiac diseases, various viruses such as influenza virus, Coxsackie A virus, cytomegalovirus, parainfluenza virus are reported in addition to Coxsackie B virus, and the major causative virus has not been ascertained yet (Akira Matsumori, Circular System Now No. 6: Cardiomyopathy/Myocarditis, Nanko-Do Co., p. 36, 1994). The search for a causative virus has been performed mainly by an indirect method in which a virus antibody is detected in a serum. There has been almost no direct proof from the cardiac muscle. One of the reasons for this is that, since a virus which has invaded the cardiac muscle disappears in several days, it is almost impossible to identify a causative virus in the cardiac muscle, particularly in a clinical scene. Web site: http://www.delphion.com/details?pn=US06214535__
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Method for treating ischemic tissue Inventor(s): Isner; Jeffrey M. (Weston, MA) Assignee(s): St. Elizabeth's Medical Center of Boston, Inc. (boston, Ma) Patent Number: 6,121,246 Date filed: October 20, 1995 Abstract: The present invention provides a method for treating ischemic tissue in a mammal which comprises injecting said tissue with an effective amount of a nucleic acid capable of expressing an angiogenic protein. The method of the present invention may be used to treat any ischemic tissue, i.e., a tissue having a deficiency in blood as the result of an ischemic disease. Such tissues can include, for example, muscle, brain, kidney and lung. Ischemic diseases include, for example, cerebrovascular ischemia, renal ischemia, pulmonary ischemia, limb ischemia, ischemic cardiomyopathy and myocardial ischemia. Excerpt(s): The present invention is directed to a method for enhancing blood vessel development in ischemic tissues. The therapeutic implications of angiogenic growth factors were first described by Folkman and colleagues over two decades ago (Folkman, N Engl J Med, 285:1182-1186 (1971)). Recent investigations have established the feasibility of using recombinant angiogenic growth factors, such as fibroblast growth
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factor (FGF) family (Yanagisawa-Miwa, et al., Science, 257:1401-1403 (1992) and Baffour, et al., J Vasc Surg, 16:181-91 (1992)), endothelial cell growth factor (ECGF)(Pu, et al., J Surg Res, 54:575-83 (1993)), and more recently, vascular endothelial growth factor (VEGF) to expedite and/or augment collateral artery development in animal models of myocardial and hindlimb ischemia (Takeshita, et al., Circulation, 90:228-234 (1994) and Takeshita, et al., J Clin Invest, 93:662-70 (1994)). In studies with recombinant angiogenic growth factors, intra-muscular administration of the growth factor was repeated over a range of 10 to 14 days. Thus, one major limitation of recombinant protein therapy is its potential requirement to maintain an optimally high and local concentration over time. Gene delivery systems employed to date have been characterized by two principal components: a macro delivery device designed to deliver the DNA/carrier mixture to the appropriate segment of the vessel, and microdelivery vehicles, such as liposomes, utilized to promote transmembrane entry of DNA into the cells of the arterial wall. Macrodelivery has typically been achieved using one of two catheters initially developed for local drug delivery: a double-balloon catheter, intended to localize a serum-free arterial segment into which the carrier/DNA mixture can be injected, or a porous-balloon catheter, designed to inject gene solutions into the arterial wall under pressure. Jorgensen et al., Lancet 1:1106-1108 (1989); Wolinsky, et al., J. Am. Coll. Cardiol., 15:475-485 (1990); March et al., Cardio Intervention, 2:11-26 (1992)); WO93/00051 and WO93/00052. Web site: http://www.delphion.com/details?pn=US06121246__ •
Method of treating diabetic cardiomyopathy Inventor(s): Hausheer; Frederick H. (Boerne, TX), Parker; Aulma (San Antonio, TX), Peddaiahgari; Seetharamulu (San Antonio, TX) Assignee(s): Bionumerik Pharmaceuticals, Inc. (san Antonio, Tx) Patent Number: 6,043,274 Date filed: October 21, 1999 Abstract: This invention relates to a method of treating patients afflicted with diabetic cardiomyopathy. The method includes administering to a patient in need of treatment an effective amount of a thiol or reducible disulfide compound according to the formula set forth in the specification. Excerpt(s): This invention relates to a method for preventing and/or treating a patient suffering from diabetic cardiomyopathy. The method involves administering an effective amount of a disulfide or thiol-containing compound to a patient suffering from diabetic cardiomyopathy. One of the many common complications of diabetes is cardiomyopathy, or abnormality of the heart. Diabetic cardiomyopathy is thought to be mediated by the progressive glycosylation of proteins, leading to progressive degeneration of the heart muscle. Diabetic cardiomyopathy generally affects the heart muscle and results in abnormalities categorized by enlargement of the myocardium, systemic embolism, myocardial failure with congestion and conduction abnormalities or arrhythmias. Diabetic cardiomyopathy generally results in a chronic degradation of heart function, to the point where the condition becomes severely life-threatening. Web site: http://www.delphion.com/details?pn=US06043274__
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Method of treating dilated cardiomyopathy Inventor(s): Komamura; Kazuo (2-15-5, Kitayamato, Ikoma-shi, Nara 630-01, JP), Miyatake; Kunio (2-8-3, Aoshinke, Minoo-shi, Osaka 562, JP), Nakamura; Toshikazu (41, Takamidai, Takatsuki-shi, Osaka 569, JP) Assignee(s): None Reported Patent Number: 6,036,972 Date filed: October 14, 1997 Abstract: The invention describes to a method of treating a patient with dilated cardiomyopathy comprising administering an effective amount of Hepatocyte Growth Factor (HGF). Excerpt(s): The present invention relates to a method of treating a patient of dilated cardiomyopathy comprising administering an effective amount of Hepatocyte Growth Factor (HGF). One of the critical symptoms of patients with dilated cardiomyopathy is a reduction of ventricular performance, resulting in an expansion of the left ventricle. The patients often have reduction in left ventricular cardiac output, increase in left ventricular diastolic pressure, and congestive heart failure. Since not all patients with dilated cardiomyopathy have congestive heart failure, the name of dilated cardiomyopathy is more practical than the name of congestive cardiomyopathy in this meaning. The symptom is acute or latent and the patients are likely to have intractable heart failure in the terminal stage. Pathologically, dilated cardiomyopathy is accompanied with diffuse or local degeneration, fibrosis and atrophy of cardiac myocardium, and the rest of cardiac myocytes is frequently found to be hypertrophied. Dilated cardiomyopathy is thought to be caused by the taking of excess alcohol, virus infection, spasm of microvessels, disorder of immunity and so on, however the real cause has not been clearly understood. Since some dilated cardiomyopathy may occur in a pedigree, it is suggested that a genetic background might be involved. Dilated cardiomyopathy may cause heart failure, lethal arrhythmia or thromboembolism, and its prognosis is poor. Ischemic cardiomyopathy may cause heart failure, and hypertensive heart diseases. In treatment of dilated cardiomyopathy, it is not enough to control an each factor independently but is necessary to control several factors simultaneously. Web site: http://www.delphion.com/details?pn=US06036972__
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Methods and apparatus for reinforcement of the heart ventricles Inventor(s): Wardle; John L. (San Clemente, CA) Assignee(s): Corset, Inc. (los Angeles, Ca) Patent Number: 6,432,039 Date filed: July 1, 1999 Abstract: A device for treating heart disorders, and particularly cardiomyopathy. The device is comprised of a compliant containment structure shaped in a configuration such that it surrounds and encases the heart. Within this containment structure are housed two or more inflation pockets that are fabricated from a non-elastic compliant material. These pockets are disposed on the interior surface of the containment structure and are configured to oppose and support the external wall of at least one of the ventricles of the heart. In the preferred embodiment, there are a plurality of relatively
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small, spaced inflation pockets disposed to act against each ventricle which is to be contained. Excerpt(s): The present invention relates to devices and methods for treating cardiomyopathy, a chronic disorder of the heart muscle, and more particularly to an implantable ventricular restraint device which is adapted to confine and control ventricular diastolic expansion. Cardiac dilation occurs with various diseases of the heart, including heart failure. In some instances, such as ischemic heart disease, the dilation may be localized to only a portion of the heart. On the other hand, cardiomyopathy usually results in global impairment. In the case of hypertrophic cardiomyopathy, there is typically increased resistance to filling of the left ventricle with accompanying dilation of the left atria. In dilated cardiomyopathy, the dilation is typically of the left ventricle with resultant failure of the heart as a pump. As the ventricles become enlarged, the situation is worsened by the resultant leakage which develops around the valvular structures. A sharply reduced ejection fraction is the hallmark of this condition. Dynamic cardiomyoplasty is one treatment currently being used to treat cardiomyopathy. One current approach being used to treat this disorder is a procedure that involves wrapping and attaching a portion of a patient's own latisimus dorsi muscle around the heart, as described, for example, in the article Reverse Remodeling from Cardiomyoplasty in Human Heart Failure, Circulation, May 1, 1995, Vol. 91, No. 9 (Kass et al.). A pacemaker-like electrical stimulator is then attached to both the heart and the wrapped muscle. After a healing period, the wrapped muscle is electrically stimulated in synchrony with the heart which causes the muscle to contract at the appropriate time. This action actively squeezes the ventricles of the heart, to augment their function. A reversal of the heart's chronic dilated condition has been found to result in many cases, and current medical opinion is that patients with chronic heart failure may be cured of symptoms by providing assistance to ventricular function using this or similar methods. Some have also considered the benefits of merely wrapping or constraining the heart with skeletal muscle without providing active systolic assist. In any event, it will be appreciated that, although this method of treatment has proven effective, it is an open surgical procedure, which involves both removal of the patient's latisimus dorsi muscle and reattachment of the same to the heart. The frequency of the electrical stimulation, if employed, is the only adjustment that a medical professional can make to optimize the treatment for individual patients using this technique. Web site: http://www.delphion.com/details?pn=US06432039__ •
Methods for identifying cardiovascular agents Inventor(s): Karas; Richard H. (Franklin, MA), Mendelsohn; Michael E. (Wellesley, MA) Assignee(s): New England Medical Center Hospitals, Inc. (boston, Ma) Patent Number: 6,692,928 Date filed: October 12, 1999 Abstract: The invention features assays to identify cardiovascular agents, such as vasoprotective agents, antihypertensive agents, cardiomyopathy therapeutic agents, coronary heart disease therapeutic agents, or heart failure therapeutic agents. The assays include culturing cells in the presence or absence of a predetermined amount of the candidate agent and measuring the expression or activity of selected genes or reporter constructs known to be responsive to estrogen.
Patents 173
Excerpt(s): Vascular diseases are the major cause of morbidity and mortality in the United States. Despite decades of intensive research, the mechanisms responsible for these diseases are poorly understood. The low incidence of vascular diseases in premenopausal women and the rapid increase in vascular diseases, including cerebrovascular and ischemic heart disease, in women following menopause are well recognized. It is now recognized that the hormone estrogen plays a significant role in preventing atherosclerotic vascular disease. Most attempts to explain the effects of estrogen on the development of vascular disease in women focus on indirect effects of estrogen on known risk factors, such as lipid and/or carbohydrate metabolism, counterbalancing of androgen-mediated effects, or indirect effects of sex hormones on the thrombotic milieu. Estrogen replacement therapy has been rather successful in reducing the incidence of vascular disease in post-menopausal women. It can reduce the incidence of coronary artery disease by as much as 30-50 percent. However, estrogen replacement therapy has a number of significant drawbacks, including an increased risk of endometrial cancer, an increased risk of breast cancer in women, and side effects such as endometrial bleeding and breast tenderness. In addition, though estrogen therapy may theoretically have beneficial effects for vascular disease in men as well as women, attempts to examine this possibility have been limited by adverse effects observed with currently available agents and the possibility of feminization that such therapy harbors. Web site: http://www.delphion.com/details?pn=US06692928__ •
Mouse lacking heart-muscle adenine nucleotide translocator protein and methods Inventor(s): Graham; Brett H. (Decatur, GA), MacGregor; Grant R. (Atlanta, GA), Wallace; Douglas C. (Atlanta, GA) Assignee(s): Emory University (atlanta, Ga) Patent Number: 6,013,858 Date filed: October 31, 1997 Abstract: Provided are transgenic mice genetically engineered for a deficiency of the heart-skeletal muscle isoform of the adenine nucleotide translocator protein (Ant1). These mice exhibit histological, biochemical and physiological signs of deficiency in oxidative phosphorylation and energy generation, and these mice provide the first animal model for mitochondrial myopathy and hypertrophic cardiomyopathy. This animal model is used in methods for testing compounds for therapeutic value in treating failure to exchange ATP and ADP across the mitochondrial inner membrane, OXPHOS deficiency and in treating cardiac hypertrophy. Excerpt(s): The field of the invention is in the area of transgenic mice, specifically, a transgenic mouse lacking the mitochondrial protein called heart-muscle adenine nucleotide translocator, and in the testing of genetic therapies and/or pharmaceuticals in animal model systems, particularly those genetic therapies and/or pharmaceuticals of benefit in protecting against or ameliorating mitochondrial myopathy and/or certain mitochondrial disease in a human or animal susceptible to or suffering from same. Mitochondrial oxidative phosphorylation (OXPHOS) is a complex biochemical process central to aerobic energy metabolism. Oxidative energy (in the form of electrons donated by NADH or FADH.sub.2) is transformed by the electron transport chain (Complexes I-IV) into a chemiosmotic gradient across the inner mitochondrial membrane that is utilized by ATP synthase (Complex V) to phosphorylate ADP, providing ATP as an energy source for the cell. Heart-muscle adenine nucleotide translocator, encoded by the ANT1 locus, is the most abundant mitochondrial protein.
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ANT1 is encoded by a nuclear gene, and the functional unit is a 60 kDa homodimer embedded in the inner mitochondrial membrane. ANT plays a central role in OXPHOS by acting as a solute carrier which imports ADP from the cytosol into the mitochondrial matrix (to be phosphorylated by ATP synthase) and exports newly phosphorylated ATP from the matrix into the cytosol. Thus, it plays a critical role in energy metabolism. ANT exists in multiple isoforms in many species. In mammals, these ANT isoforms exhibit tissue-specific gene expression patterns (Stepien et al. (1992) J. Biol. Chem. 267:1459214597 and hereinbelow). Ant1 is considered a heart/muscle specific isoform due to its predominant expression in cardiac and skeletal muscle. Web site: http://www.delphion.com/details?pn=US06013858__ •
Mouse model for congestive heart failure Inventor(s): Leiden; Jeffrey M. (51 Cresent Dr., Glencoe, IL 60022) Assignee(s): None Reported Patent Number: 6,194,632 Date filed: December 18, 1998 Abstract: The present invention relates to transgenic mice which express CREB. These transgenic mice provide a genetic model of dilated cardiomyopathy. Excerpt(s): Congestive heart failure (CHF) is a leading cause of cardiovascular morbidity and mortality affecting more than 4 million Americans and representing the most common reason for hospitalization of patients over the age of 65 (1, 2). Idiopathic dilated cardiomyopathy (IDC), a primary myocardial disease of unknown etiology characterized by ventricular dilatation and depressed myocardial contractility is an important cause of CHF with an estimated prevalence of 36 cases/100,000 (3-7). Relatively little is known about the molecular mechanisms underlying the pathogenesis of IDC. Progress in this area has been limited by the lack of animal models that closely resemble the anatomical and clinical features of the human disease. Several previously described genetically modified mice have been reported to develop cardiomyopathies. These include mice expressing mutant forms of {character pullout}-myosin heavy chain ({character pullout}-MHC), mice engineered to ectopically express the myf5 bHLH transcription factor in the heart, and mice containing targeted mutations of the muscle LIM protein (MLP) (49-51). However, the phenotypes of each of these mice differs significantly from that of the transgenic mice described herein. Unlike the transgenic mice of the present invention, which display progressive cardiac dilatation without hypertrophy, the {character pullout}-MHC and myf5 mice develop a hypertrophic cardiomyopathy with myocyte disarray and interstitial fibrosis (50, 51). Consistent with these histological findings, the {character pullout}-MHC mice display normal end systolic LV pressures and dP/dtmax but abnormal LV relaxation. These findings are highly reminiscent of the phenotype of patients with hypertrophic as opposed to dilated cardiomyopathy. The phenotype of the transgenic mice of the present invention also differed significantly from that of the recently described muscle LIM protein (MLP)deficient mice which display soft, markedly hypertrophic hearts with grossly abnormal sarcomere structure within the first several weeks after birth (49). Unlike the transgenic mice of the present invention, 50-70% of the MLP-deficient mice die before 10 days of age. Web site: http://www.delphion.com/details?pn=US06194632__
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Percutaneous mitral annuloplasty and cardiac reinforcement Inventor(s): Langberg; Jonathan J. (Atlanta, GA), van der Burg; Erik (Sunnyvale, CA), Lesh; Michael D. (Mill Valley, CA) Assignee(s): Ev3 Santa Rosa, Inc. (santa Rosa, Ca) Patent Number: 6,537,314 Date filed: January 30, 2001 Abstract: A mitral annuloplasty and left ventricle restriction device is designed to be transvenously advanced and deployed within the coronary sinus and in some embodiments other coronary veins. The device places tension on adjacent structures, reducing the diameter and/or limiting expansion of the mitral annulus and/or limiting diastolic expansion of the left ventricle. These effects may be beneficial for patients with dilated cardiomyopathy. Excerpt(s): The present invention relates to intravascular prostheses for remodeling an extravascular anatomical structure. In one application, the present invention relates to a mitral annuloplasty and cardiac reinforcement device which is transluminally implantable in the coronary sinus. Dilated cardiomyopathy occurs as a consequence of many different disease processes that impair myocardial function, such as coronary artery disease and hypertension. The left ventricle enlarges and the ejection fraction is reduced. The resulting increase in pulmonary venous pressure and reduction in cardiac output cause congestive heart failure. Enlargement of the mitral annulus and left ventricular cavity produce mitral valvular insufficiency. This in turn, causes volume overload that exacerbates the myopathy, leading to a vicious cycle of progressive enlargement and worsening mitral regurgitation. According to recent estimates, more than 79,000 patients are diagnosed with aortic and mitral valve disease in U.S. hospitals each year. More than 49,000 mitral valve or aortic valve replacement procedures are performed annually in the U.S., along with a significant number of heart valve repair procedures. Web site: http://www.delphion.com/details?pn=US06537314__
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Pyridazinone aldose reductase inhibitors Inventor(s): Mylari; Banavara L. (Waterford, CT) Assignee(s): Pfizer Inc (new York, Ny) Patent Number: 6,579,879 Date filed: March 21, 2002 Abstract: The present invention relates to novel pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to methods of affording cardioprotection to subjects not suffering from diabetes. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of this invention and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals. This invention
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also relates to other combinations with the ARIs of this invention, including combinations with adendsine agonists; NHE-1 inhibitors; glycogen phosphorylase inhibitors; selective serotonin reuptake inhibitors; GABA agonists; antihypertensive agents; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors; phosphodiesterase-5 inhibitors; and to glucose lowering agents. Excerpt(s): The present invention relates to novel sulfonyl pyridazinone compounds, pharmaceutical compositions comprising those compounds and to methods of using such compounds and compositions to inhibit aldose reductase, lower sorbitol levels and, thus, lower fructose levels, and/or treat or prevent diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. This invention also relates to pharmaceutical compositions and kits comprising a combination of an aldose reductase inhibitor (ARI) of Formula I herein and a sorbitol dehydrogenase inhibitor and to methods of using such compositions or kits to treat or prevent the above diabetic complications in mammals. This invention also relates to other combinations with the ARIs of Formula I, including combinations with NHE-1 inhibitors; adenosine agonists; glycogen phosphorylase inhibitors (GPIs); selective serotonin reuptake inhibitors (SSRIs);.gamma.-amino-butyric acid (GABA) agonists; antihypertensive agents; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (vastatins); phosphodiesterase-5 (PDE5) inhibitors; and to glucose lowering compounds. This invention also relates to pharmaceutical compositions and kits comprising such combinations and to methods of using such compositions and kits to treat or prevent the aforesaid diabetic complications. This invention also relates to novel compounds that are useful as intermediates for preparing the sulfonyl pyridazinone compounds of this invention. The enzyme aldose reductase is involved in regulating the reduction of aldoses, such as glucose and galactose, to their corresponding polyols, such as sorbitol and galactitol. Sulfonyl pyridazinone compounds of Formula I of this invention, prodrugs of such compounds and pharmaceutically acceptable salts of such compounds and prodrugs, are useful as aldose reductase inhibitors in the treatment and prevention of diabetic complications of humans and other mammals associated with increased polyol levels in certain tissues (e.g., nerve, kidney, lens and retina tissue) of affected humans and other mammals. French Patent Publication No. 2647676 discloses pyridazinone derivatives having substituted benzyl side chains and benzothiazole side chains described as being inhibitors of aldose reductase. Web site: http://www.delphion.com/details?pn=US06579879__ •
Quinone derivatives for treating or preventing diseases associated with iron overload Inventor(s): Rotig; Agnes (Paris, FR), Rustin; Pierre (Paris, FR) Assignee(s): Institut National DE LA Sante ET DE LA Recherche Medicale (inserm) (paris, Fr) Patent Number: 6,133,322 Date filed: May 20, 1999 Abstract: A method of treating or preventing a disorder resulting from a mitochondr dysfunction induced by an iron overload including Friedreich Ataxia, hypertrophic cardiomyopathy, Hallervorden-Spatz disease, sideroblastic anemia by administering an effective amount of an ubiquinone derivative such as idebenone, decylubiquiqnone, coenzyme Q2, coenzyme Q4, and coenzyme Q6, either alone or in conjunction with a second therapeutic agent or a non-reducing antioxidant.
Patents 177
Excerpt(s): The present invention relates to a method of treating or preventing disorders associated with a intracellular iron overload, and more particularly Friedreich Ataxia (FRDA), Hallervorden-Spatz disease, or sideroblastic anemia associated with iron overload. More particularly, the invention relates to the administration of quinone derivatives such as coenzyme Q.sub.10 (ubiquinone) and its short-chain analogues (coenzyme Q.sub.4 and idebenone) to protect the heart and brain of FRDA patients from iron-induced injury. The Friedreich ataxia (FRDA) is a frequent autosomal degenerative disease (1/30,000 live birth). It is characterized by spinocerebellar degeneration resulting in progressive limb and gait ataxia with lack of tendon reflexes in the legs and in pyramidal syndrome of the inferior limbs, and by hypertrophic cardiomyopathy. Geoffroy et al., Clinical description and roentgenologic evaluation of patients with Friedreich's ataxia, Can. J. Neurol. Sci. 3, 279-286 (1976); Harding, Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features, Brain, 104, 598-620 (1981). The disease gene has been mapped to chromosome 9q13 and encodes an ubiquitous 210-aminoacid protein, frataxin, targeted to the mitochondria. Chamberlain et al., Genetic homogeneity of the Friedreich ataxia locus on chromosome 9, Am. J. Human. Genet., 44, 518-521 (1989); Campuzano et al., Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion, Science, 271, 1423-1427 (1996); KoutnikovA et al., Studies of human, mouse and yeast homologue indicate a mitochondrial function for the frataxin, Nature Genet., 16, 345-351 (1997); Priller et al., Frataxin gene of Friedreich's ataxia is targeted to mitochondria, Ann. Neurol, 42, 265-269 (1997); Babcock et al., Regulation of mitochondrial iron accumulation by Yfh 1p, a putative homologue of fraxatin, Science, 276, 1709-1712 (1997); Foury et al., Deletion of the yeast homologue of the human gene associated with Friedreich's ataxia elicits iron accumulation in mitochondria, FEBS Lett., 411, 373-377 (1997); Wilson et al., Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue, Nature Genet., 16, 352-357 (1997). FRDA is primarily caused by a GAA repeat expansion in the first intron of the fraxatin gene, which accounts for 98% of mutant alleles. Campuzano et al., Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion, Science, 271, 1423-1427 (1996). Yet, the tissue-specific expression of the disease remains unexplained and no animal model is presently available in FRDA. The inventors have recently reported in Rotig et al., Aconitase and mitochondrial ironsulphur protein defiency in Friedreich ataxia, Nature Genet., 17, 215-217 (1997) a deficient activity of the iron-sulphur (Fe-S) cluster containing proteins (ISP) in endomyocardical biopsies of FRDA patients, namely complexes I, II and III of the mitochondrial respiratory chain and aconitase, which cytosolic activity regulates cell iron homeostasis. Accordingly, ISPs have been shown to rapidly lose their catalytic activity in both FRDA patients and yeast strains carrying a deleted frataxin gene counterpart. Web site: http://www.delphion.com/details?pn=US06133322__ •
Reinforcement device Inventor(s): Snyders; Robert V. (Ballwin, MO) Assignee(s): Cardio Technologies, Inc. (pine Brook, Nj) Patent Number: 6,095,968 Date filed: April 8, 1999
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Abstract: A heart assist device intended for the long term support of certain late-stage cardiac failure states, particularly those known in the practice of cardiology to be called a dilated cardiomyopathy. A method is described wherein a "viscous cardioplasty jacket" is fashioned to provide a buttressing effect to the ventricular heart walls to thus render a more efficient cardiac contractile mechanism whereby the patient is afforded improved heart function to allow increased physical activities. Such a viscous compliant enclosure of the ventricular heart masses can be utilized concurrently with recognized drug therapy which is sometime lacking in beneficial effect for these patients and is far less traumatic than the currently practiced surgical cardiomyoplasty (CMP) procedure. Application of this device may be accomplished through a relatively non-invasive endoscopic procedure in a more refined methodology of anatomical implantation of the device. Excerpt(s): This invention very simply constitutes a modification of use with minimal fabrication changes of the original device as defined in U.S. Pat. No. 5,256,132 (Snyders) which invention is designed for acute heart failure support via a cyclical pneumatic ventricular compression in timed synchrony with the ambient heart rhythm. The present methodology pertains to the provision of long-term support for individuals suffering from certain late-stage heart failure disease entities as are particularly known in medical practice as the dilated cardiomyopathies. These disease states are of frequent occurrence and carry a high mortality rate if not corrected in a reasonable period of time. This modification consists of the instillation of a high viscosity silicone (or other) fluid into the encircling retention sac space of the previously described device (U.S. Pat. No. 5,256,132) to enclose the heart ventricles, with a resultant reduction in ventricular systolic and diastolic volumes of the heart. Such volume reductions are known to reduce myocardial oxygenation requirements for any given level of cardiac contractility needed for ongoing adequate cardiac functional requirements for any given level of physical activity by the patient. Such a modification and application of the previously described VAD (Ventricular Assist Device), though minimally changed in its original fabrication, could open a new area of interventional long-term support for those patients afflicted with a dilated cardiomyopathy. The VAD jacket is quite easily adjustable to any cardiac size and is virtually self-sizing relative to circumferential dimension requirements even for the very largest hearts because of the diminutive fabrication features of the device for insertion around the heart and inside the pericardial sac, which location is its appropriate compliant anatomical site of implantation. Subsequent filling of the sac space with a viscous silicone or other equivalent non-compressible fluid through the fill line of the device to enclose the ventricular masses with either no or minimal pressurization therein as registered in a sac pressure monitor line then results in a viscous cardioplasty reinforcement of the thinned ventricular walls with a resultant reduction in LV (Left Ventricular) and RV (Right Ventricular) diameters to effect a desirable reduction of wall stress. This procedure thus effectively provides for a "reverse remodeling" of the heart via both a diastolic and systolic volumetric restriction but not constriction of the ventricular anatomy and with a subsequent improved physiological benefit to cardiac function. The Law of LaPlace defines that this physiological benefit is sequential to reduced wall stress (wall tension) consequent upon the reduction in chamber diameter and increased chamber wall thickness provided by such a girdling "cardioplasty" event, and such an alteration results in reduced myocardial oxygen needs sequential to that reduction in wall stress. Such reduced oxygen needs at rest then convert to increased myocardial oxygen availability for increased physical activity and a resultant improved functional class for the patient. It will be noted below that an important provision of a high viscosity fluid (e.g. to 12,500 ctsk.) for sac filling is suggested for use because of the increased inertial character of those higher viscosity
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fluids such that areas of ventricular akinesia or dyskinesia subject to paradoxical wall motion in systole should be somewhat restrained from such an undesirable dysfunctional event with the ventricular wall enclosure as proposed. Such restraint would provide a beneficial improvement in systolic ejection volumes and thus be additive to the beneficial girdling restraint derived from the cardioplasty jacket application itself. Web site: http://www.delphion.com/details?pn=US06095968__ •
Synergistic effect of a sulfonylurea and/or non-sulfonylurea K+ATP channel blocker, and a phosphodiesterase 3 type inhibitor Inventor(s): Fryburg; David A. (East Lyme, CT), Parker; Janice C. (Ledyard, CT) Assignee(s): Pfizer Inc. (new York, Ny) Patent Number: 6,610,746 Date filed: April 10, 2001 Abstract: The present invention provides methods of treating non-insulin dependent diabetes mellitus, insulin resistance, Syndrome X, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, polycystic ovary syndrome, cataracts, hyperglycemia, or impaired glucose tolerance, the methods comprising the step of administering to a patient having or at risk of having non-insulin dependent diabetes mellitus, insulin resistance, Syndrome X, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, polycystic ovary syndrome, cataracts, hyperglycemia, or impaired glucose tolerance a synergistic amount of:1) a sulfonylurea, a non-sulfonylurea K.sup.+ ATP channel blocker, or a sulfonylurea and a non-sulfonylurea K.sup.+ ATP channel blocker; and 2) a cAMP phosphodiesterase type 3 inhibitor. The present invention also provides kits and pharmaceutical compositions that comprise: 1) a sulfonylurea, a non-sulfonylurea K.sup.+ ATP channel blocker, or a sulfonylurea and a non-sulfonylurea K.sup.+ ATP channel blocker; and 2) a cAMP phosphodiesterase type 3 inhibitor. The present invention also relates to kits and pharmaceutical compositions that comprise 1) a sulfonylurea, a non-sulfonylurea K.sup.+ ATP channel blocker, or a sulfonylurea and a non-sulfonylurea K.sup.+ ATP channel blocker; 2) a cAMP phosphodiesterase type 3 inhibitor; and 3) an additional compound useful for the treatment of non-insulin dependent diabetes mellitus, insulin resistance, Syndrome X, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, polycystic ovary syndrome, cataracts, hyperglycemia, or impaired glucose tolerance. Excerpt(s): The present invention relates to methods of treating non-insulin dependent diabetes mellitus, insulin resistance, Syndrome X, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, polycystic ovary syndrome, cataracts, hyperglycemia, or impaired glucose tolerance, the methods comprising the step of administering to a patient having or at risk of having non-insulin dependent diabetes mellitus, insulin resistance, Syndrome X, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, polycystic ovary syndrome, cataracts, hyperglycemia, or impaired glucose tolerance a synergistic amount of: 1) a sulfonylurea, a non-sulfonylurea K.sup.+ ATP channel blocker, or a sulfonylurea and a non-sulfonylurea K.sup.+ ATP channel blocker; and 2) a cAMP phosphodiesterase type 3 inhibitor. The present invention also relates to kits and pharmaceutical compositions that comprise: 1) a sulfonylurea, a non-sulfonylurea K.sup.+ ATP channel blocker, or a sulfonylurea and a non-sulfonylurea K.sup.+ ATP channel blocker; and 2) a
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cAMP phosphodiesterase type 3 inhibitor. The present invention also relates to kits and pharmaceutical compositions that comprise: 1) a sulfonylurea, a non-sulfonylurea K.sup.+ ATP channel blocker, or a sulfonylurea and a non-sulfonylurea K.sup.+ ATP channel blocker; 2) a cAMP phosphodiesterase type 3 inhibitor; and 3) an additional compound useful for the treatment of non-insulin dependent diabetes mellitus, insulin resistance, Syndrome X, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, polycystic ovary syndrome, cataracts, hyperglycemia, or impaired glucose tolerance. In spite of the early discovery of insulin and its subsequent widespread use in the treatment of diabetes, and the later discovery of and use of sulfonylureas, biguanides and thiazolidenediones, such as troglitazone, rosiglitazone or pioglitazone, as oral hypoglycemic agents, the treatment of diabetes can be improved. A group of compounds that stimulate insulin secretion and stimulate de novo synthesis of insulin are the cAMP phosphodiesterase type 3 inhibitors. It is believed that cAMP phosphodiesterase type 3 inhibitors act to increase insulin secretion by increasing intracellular levels of cAMP in pancreatic.beta.-cells in the islet of Langerhans. In contrast, sulfonylureas act on the K.sup.+ ATP channels of pancreatic.beta.-cells in the islet of Langerhans. Moreover, cAMP phosphodiesterase type 3 is known to exist in two forms: type A and type B. Type A cAMP phosphodiesterase 3 is associated with cardiac tissue and with platelets, and type B is associated with liver and adipose tissue, and.beta.-cells in the pancreas. Web site: http://www.delphion.com/details?pn=US06610746__ •
System and method for treating dilated cardiomyopathy using end diastolic volume (EDV) sensing Inventor(s): Rosenberg; Meir (Newton, MA) Assignee(s): Abiomed, Inc. (danvers, Ma) Patent Number: 6,314,322 Date filed: March 2, 1998 Abstract: A system for controlling end diastolic volume of the heart is disclosed. The system includes an EDV sensor constructed and arranged to measure a parameter related to the end diastolic volume of the heart, and a heart stimulator, responsive to the EDV sensor, constructed and arranged to invoke systole when the measured parameter reaches a predetermined level, the parameter reaching that level prior to termination of diastole. Preferably, the heart stimulator may be a pacemaker. The EDV sensor may be any sensor constructed to measure a parameter related to the end diastolic volume of the heart, or another selected physiological or patho-physiological condition of the heart, including a strain sensor, a stress sensor, a dimension sensor, an impedance sensor, an optical sensor, a microwave sensor, or another sensor constructed to measure a parameter related to the end diastolic volume of the heart, or another selected physiological or patho-physiological condition of the heart. A method for controlling end diastolic volume of the heart including the steps of measuring a parameter that is related to the end diastolic volume of the heart, and invoking systole before termination of diastole when the measured parameter reaches a predetermined level is also disclosed. Excerpt(s): The present invention relates generally to controlling congestive heart failure and, more particularly, to electrically controlling a dilated condition resulting from congestive heart failure. The heart pumps blood through a patient's body in order to carry oxygen to, and remove carbon dioxide from, cells located throughout the body. In
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a patient having a normal heart, the rate at which the blood is pumped through the body increases or decreases to accommodate changes in the physiological needs of the patient. That is, as the cells of the patient's body require more oxygen, the heart rate and/or stroke volume increases to pump more oxygen-rich blood to the cells. When insufficient oxygen is available from the lungs, the respiration rate may also increase to increase the rate of oxygen intake into the body. Conversely, as the demand for oxygen decreases, the heart rate decreases, providing less blood flow and, hence, less oxygen, to the cells. During a heart cycle, deoxygenated, venous blood enters the right atrium of the heart via the inferior vena cava and the superior vena cava and, during diastole, flows to the right ventricle. The pulmonary artery then delivers blood ejected from the right ventricle into the lungs. The pulmonary vein carries oxygenated blood from the lungs to the left atrium of the heart. During diastole, oxygenated blood flows from the left atrium to the left ventricle, which is filled to its end diastolic volume (EDV). During systole the left ventricle ejects oxygenated blood into the aorta. Web site: http://www.delphion.com/details?pn=US06314322__ •
Transgenic model for heart failure Inventor(s): Leinwand; Leslie A. (Boulder, CO), Vikstrom; Karen L. (Fayetteville, NY) Assignee(s): University Technology Corporation (boulder, Co) Patent Number: 6,353,151 Date filed: September 26, 1997 Abstract: The present invention discloses a transgenic mouse that is a model for congestive heart failure. The disclosed mouse is a subset of a transgenic mouse line that is a model for hypertrophic cardiomyopathy. Also disclosed are a recombinant nucleic acid molecule encoding a transgene, and methods of using the transgenic mouse model to study congestive heart failure and conditions and treatments related thereto. Excerpt(s): The present invention relates to a transgenic animal model for studying heart failure. In particular, the present invention relates to methods of studying molecular/cellular events associated with congestive heart failure, of testing drug candidates for prevention or treatment of congestive heart failure, of studying the effects of factors such as diet or exercise on congestive heart failure, and of studying specific conditions or diseases associated with congestive heart failure. A variety of human diseases and conditions which are manifested by cardiac abnormalities or cardiac dysfunction can lead to heart failure. Heart failure is a physiological condition in which the heart fails to pump enough blood to meet the circulatory requirements of the body. The study of such a condition in genetically diverse humans is difficult and unpredictable. Therefore, there is a need for a model system which facilitates the study of the mechanisms and causes of heart failure as well as the identification of potential therapeutic targets. The development of transgenic animal technology has provided significant advances for obtaining more complete information about complex systems in vivo. By manipulating the expression of gene(s) in vivo, it is possible to gain insight into the roles of such genes in a particular system or to study aspects of the system in a genetically controlled environment. Although cardiac disease in a small mammal is inherently different from that seen in humans, mammals such as the mouse allow analysis of disease at molecular and cellular levels that is often impossible in humans. Web site: http://www.delphion.com/details?pn=US06353151__
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Treatment of disease states Inventor(s): Gurney; Harry C. (Conifer, CO), McMichael; John (Delanson, NY) Assignee(s): Milkhaus Laboratory, Inc. (delanson, Ny) Patent Number: 6,303,127 Date filed: August 11, 1998 Abstract: The invention presents methods for the treatment of symptoms associated with diseases states including cardiomyopathy, Parkinson's Disease and degenerative liver disease including cirrhosis comprising treatment with an effective amount of a composition comprising beta-amyloid, streptolysin O, and growth hormone. Excerpt(s): This invention relates generally to methods and materials for the treatment and amelioration of the symptoms associated with cardiomyopathy in non-human animals, Parkinson's Disease, and degenerative liver disease including cirrhosis. Cardiomyopathy is a disease of the heart muscle. This form of heart disease is often distinctive, both in general symptoms and in patterns of blood flow, to allow a diagnosis to be made. Increasing recognition of this disease, along with improved diagnostic techniques, has shown that cardiomyopathy is a major cause of morbidity and mortality. In some areas of the world it may account for as many as 30 percent of all deaths due to heart disease. Cardiomyopathy can result from a variety of structural or functional abnormalities of the ventricular myocardium. A large number of cardiomyopathies are apparently not related to an infectious process and are not well understood. Some are congenital and may cause enlargement of the heart. Metabolic diseases associated with endocrine disorders may also cause cardiomyopathies. Infections, such as acute rheumatic fever and several viral infections, may cause a number of types of myocarditis. Myocarditis may also occur as a manifestation of a generalized hypersensitivity reaction, allergic or immunologic. The heart may also be affected by any of a considerable number of collagen diseases. Collagen is the principal connective tissue protein, and collagen diseases are diseases of the connective tissues. They include diseases primarily of the joints, skin, and systemic disease. Web site: http://www.delphion.com/details?pn=US06303127__
Patent Applications on Cardiomyopathy As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to cardiomyopathy: •
Agent for gene therapy of dilated cardomyopathy Inventor(s): Toyo-Oka, Teruhiko; (Tokyo, JP) Correspondence: Greenblum & Bernstein, P.L.C.; 1941 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20010029040 Date filed: January 25, 2001
10
This has been a common practice outside the United States prior to December 2000.
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Abstract: According to the present invention, there is provided a gene expression vector which is obtained by inserting a gene encoding sarcoglycan into an adeno-associated virus (AAV) vector. By administering the gene expression vector of the present invention to a living body in vivo, a sarcoglycan can be continuously expressed in the living body, so that the restoration of.alpha.,.beta.,.gamma.- and.delta.-sarcoglycan components can be accompanied and the heart function of the patient of dilated cardiomyopathy can be improved. Excerpt(s): The present invention relates to an agent for gene therapy of dilated cardiomyopathy, more particularly, a gene expression vector which is obtained by inserting a gene encoding a sarcoglycan into an adeno-associated virus vector. Cardiomyopathy is one of the heart diseases which shows contraction dysfunction and electrophysiological dysfunction as symptoms, and includes a group of heart diseases which lead to a sever heart failure and a sudden death. Cardiomyopathy is classified into dilated cardiomyopathy and hypertrophied cardiomyopathy, and the study for revealing the causes of each cardiomyopathy has been made. In the case of dilated cardiomyopathy (DCM), in spite of progress in the therapy, the prognosis of the patients is still poor and cardiac transplantation is necessary in the deteriorated cases (V. V. Michels, et al., New Engl.J.Med. 326, 77 (1992); E. K. Kasper, et al., J.Am.Coll.Cardiol. 23, 586 (1994); M. Packer, et al., New Engl.J.Med. 334, 1349 (1996); M. Packer, et al. New Engl.J.Med. 335,1107 (1996); R. M. Graham, W. A. Owens, N.Engl.J.Med. 341, 1759 (1999)). Therefore, it is necessary to develop a novel method for therapy which can improve the patient's mortality and morbidity. Animal model is useful for developing such a novel method for therapy. Gene transfer will be promising for the therapy of some type of DCM which is caused by the gene deletion. It has been demonstrated that the deletion of.delta.-sarcoglycan (.delta.-SG) gene is the cause of DCM in hamsters (A. Sakamoto, et al., Proc.Natl.Sci.Acad.U.S.A. 94, 13873 (1997); V. Nigro, et al., Hum.Mol.Genet. 6, 601 (1997)). Also, it has been found that the breakpoint of.delta.-SG gene in TO-2 hamster which is a model animal of DCM is present in the first intron, and large region including its promoter and the first exon is deleted in TO-2 hamster (A. Sakamoto, et al., Proc.Natl.Sci.Acad.U.S.A. 94, 13873 (1997)). Furthermore, dystrophinassociated glycoprotein complex (DAGC) links intracellular contractile machinery with extracellular matrix (G. F. Cox, L. M. Kunkel, Curr.Opin.Cardiol. 12, 329 (1997); K. H. Holt, et al., Mol. Cell 1, 841 (1998); M. D. Henry, K. P. Campbell, Curr.Opin.Cell Biol. 11, 602 (1999)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Aldosterone blocker therapy to prevent or treat inflammation-related disorders Inventor(s): Rocha, Ricardo; (Flemington, NJ), Zack, Marc D.; (Winnetka, IL) Correspondence: Pharmacia Corporation; Global Patent Department; Post Office Box 1027; ST. Louis; MO; 63006; US Patent Application Number: 20040037806 Date filed: January 24, 2003 Abstract: A method of preventing or treating an inflammation-related disorder such as myocarditis, cardiomyopathy, vasculitis, and Behcet's disease in a subject, comprising treating the subject with a therapeutically-effective amount of an aldosterone blocker sufficient to alter the expression of one or more expression products involved, directly or indirectly, in the regulation of inflammation or cardiac remodeling in the subject.
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Excerpt(s): This invention is in the field of preventing or treating inflammation-related disorders, and more particularly inflammation-related cardiovascular disorders. More specifically, this invention relates to the use of aldosterone blocker therapy in preventing or treating cardiovascular disease including atherosclerosis. Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG.sub.2, PGH.sub.2 and PGE.sub.2, has been a common target of anti-inflammatory drug discovery. However, common non-steroidal anti-inflammatory drugs (NSAID's) that are active in reducing the prostaglandininduced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAID's can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAID's is the use of corticosteroids, which also produce severe adverse effects, especially when long term therapy is involved. NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated with inflammation (named "cyclooxygenase-2 (COX-2)" or "prostaglandin G/H synthase II") provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cardiac reinforcement device Inventor(s): Wardle, John L.; (San Clemente, CA) Correspondence: Donald E. Stout; Stout, Uxa, Buyan & Mullins, Llp; Suite 300; 4 Venture; Irvine; CA; 92618; US Patent Application Number: 20020065449 Date filed: January 28, 2002 Abstract: A unique device is provided for treating heart disorders, and particularly cardiomyopathy. The inventive device is comprised of a compliant containment structure shaped in a configuration such that it surrounds and encases the heart. Within this containment structure are housed two or more inflation pockets that are fabricated from a non-elastic compliant material. These pockets are disposed on the interior surface of the containment structure and are configured to oppose and support the external wall of at least one of the ventricles of the heart. In the preferred embodiment, there are a plurality of relatively small, spaced inflation pockets disposed to act against each ventricle which is to be contained. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/113,232, filed Dec. 21, 1998, which is commonly owned and the contents of which are expressly incorporated herein by reference. The present invention relates to devices and methods for treating cardiomyopathy, a chronic disorder of the heart muscle, and more particularly to an implantable ventricular restraint device which is adapted to confine and control ventricular diastolic expansion. Cardiac dilation occurs with various diseases of the heart, including heart failure. In some instances, such as ischemic heart disease, the dilation may be localized to only a portion of the heart. On the other hand, cardiomyopathy usually results in global impairment. In the case of hypertrophic cardiomyopathy, there is typically increased resistance to filling of the left ventricle with accompanying dilation of the left atria. In dilated cardiomyopathy, the dilation is
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typically of the left ventricle with resultant failure of the heart as a pump. As the ventricles become enlarged, the situation is worsened by the resultant leakage which develops around the valvular structures. A sharply reduced ejection fraction is the hallmark of this condition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cardiac reinforcement device Inventor(s): Alferness, Clifton A.; (Redmond, WA) Correspondence: Attention: Melisaa Jean Pytel; Merchant & Gould P.C.; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20020091296 Date filed: February 25, 2002 Abstract: The present disclosure is directed to a cardiac reinforcement device (CRD) and method for the treatment of cardiomyopathy. The CRD provides for reinforcement of the walls of the heart by constraining cardiac expansion, beyond a predetermined limit, during diastolic expansion of the heart. A CRD of the invention can be applied to the epicardium of the heart to locally constrain expansion of the cardiac wall or to circumferentially constrain the cardiac wall during cardiac expansion. Excerpt(s): The present invention is generally directed to a device and method for reinforcement of the cardiac wall. The invention is particularly suited for the treatment of cardiac disease which result in atrial or ventricular dilation. The invention provides reinforcement of the cardiac wall during diastolic chamber filling to prevent or reduce cardiac dilation in patients known to have experienced such dilation or who have a predisposition for such dilation occurring in the future. The cardiac reinforcement structure is typically applied to the epicardial surface of the heart. Cardiac dilation occurs with different forms of cardiac disease, including heart failure. In some cases, such as post-myocardial infarction, the dilation may be localized to only a portion of the heart. In other cases, such as hypertrophic cardiomyopathy, there is typically increased resistance to filling of the left ventricle with concomitant dilation of the left atria. In dilated cardiomyopathy, the dilation is typically of the left ventricle with resultant failure of the heart as a pump. In advanced cases, dilated cardiomyopathy involves the majority of the heart. With each type of cardiac dilation, there are associated problems ranging from arrhythmias which arise due to the stretch of myocardial cells, to leakage of the cardiac valves due to enlargement of the valvular annulus. Devices to prevent or reduce dilation and thereby reduce the consequences of dilation have not been described. Patches made from low porosity materials, for example Dacron.TM., have been used to repair cardiac ruptures and septal defects, but the use of patches to support the cardiac wall where no penetrating lesion is present has not been described. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cardio therapeutic heart sack Inventor(s): Okuzumi, Yuzi; (Parker, CO) Correspondence: Attention: Melissa Jean Pytel; Merchant & Gould P.C.; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20020151950 Date filed: June 13, 2001 Abstract: This invention relates to implantable heart sack that can be equipped with pacemaker leads and/or defibrillation leads for the treatment of cardiomyopathy, hypertrophic cardiomyopathy, tachycardia, bradycardia, ventricular fibrillation, atrial fibrillation etc. The hear sack was prepared from biocompatible, biostable, implantable polyetherurethane, polycarbonateurethane, silicone, polysiloxaneurethane, polyfluoroethylene, or hydrogenated poly(styrene-butadiene) copolymer. The heart sack is equipped with attached sutures to make it easier to attach onto the heart. The heart sack can be made semipermeable or perforated to have numerous holes. The heart sack can be reinforce with fiber or filament. Ordinary pacemaker leads can be attached to the inner side of the heart sack. However, the pacemaker leads of this invention were prepared from noble metal (gold, platinum, rhodium and platinum-Rhodium alloys) or stainless steel coated, deposited or plated mono-filaments, yarns, braids, cords, wires or films, or cylindrical tubes of polyamide, polyimide, polyester, and/or polypropylene that are encased in multi-lumen insulating tube or coaxial tube made of biocompatible, biostable, implantable polyetherurethane, polycarbonateurethane, silicone, polysiloxaneurethane, polyfluoroethylene, or hydrogenated poly(styrene-butadiene) copolymer. The leads can be mounted onto the inner surface of the heart sack and contoured to the heart. The heart sack can be coated with hydrophilic coating containing an antimicrobial agent that gives the heart sack a low coefficient of friction, excellent biocompatibility and antimicrobial properties. Excerpt(s): This invention relates to a biocompatible, biostable and implantable heart sack which is prepared from biocompatible, biostable and implantable elastomers selected from the group consisting of polyetherurethane, polycarbonateurethane, silicone, poly(siloxane) urethane and/or hydrogenated poly(styrene-butadiene) copolymer for the treatment of cardiomyopathy, hypertrophic cardiomyopathy, tachycardia, bradycardia, ventricular fibrillation, atrial fibrillation etc. The heart sack of this invention can be reinforced with mono-filaments, yarns, braids, cords, knitted or woven or non-woven cloth made of a biocompatible, biostable, implantable polyamide, polyimide, polyester, polypropylene, and/or polyurethane etc. The heart sack of this invention can be equipped with pacemaker leads and defibrillation leads. The leads and electrodes of this invention are made of noble metal or stainless steel deposited, coated or plated mono-filaments, yarns, braids, cords, wires, films, cloth and/or cylindrical tubes. The noble metal used for this invention is selected from the group consisting of gold, platinum, rhodium and their alloys. The mono-filaments, yarns, braids, cords, wires, films, cloth or cylindrical tubes materials to be coated, deposited or plated with noble metal are selected from the group consisting of poly(ethylene terephthalate), poly(butylene terephthalate), polyamide, polyimide, polypropylene, polyetherurethane, polycarbonateurethane and their copolymers. The heart sack and electrodes are very flexible and have good biocompliance with heart muscle. They have high strength and excellent mechanical properties. Ordinary pacemaker leads and defibrillation leads could be also imbedded into the heart sack to provide cardiac pacing or defibrillation. Electrical therapeutic heart sack devices are a new and noble concept. Cardiomyopathy is a commonly observed disease in an aging population. Cardiomyopathy is a defect of
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myocardial function. There are three categories of Cardiomyopathies; dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy. Dilated cardiomyopathy refers to a condition in which there is weakened contraction of the ventricles with an apparent dilation of the ventricles. This leads to inadequate perfusion, and increased pulmonary and systemic venous congestion. It will lead essentially to loss of heart function. The history of the disease is one of progressive deterioration. The mortality in one year is greater than 50% for those people who have a poorly functioning heart. Hyper cardiomyopathy is a disease of the heart muscle. It is characterized with an overactive left ventricle due to its increase in muscle mass resulting in an obstruction of the blood that is being pumped from the left ventricle to the rest of the body. This causes dyspnea on exertion and chest pain due to ischemia. Currently, there is no treatment to alter the course of the disease. Restrictive cardiomyopathy is least common of cardiomyopathies. It is due to other pathological processes such as scerderma, amyloid, sarcoid, or storage decease. This invention is to prevent enlargement of the heart and thinning of the heart wall of patients with dilated cardiomyopathy, or hypertrophic cardiomyopathy by the use of a heart sack. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination of GABA agonists and aldose reductase inhibitors Inventor(s): Mylari, Banavara L.; (Waterford, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020077319 Date filed: November 29, 2001 Abstract: This invention relates to pharmaceutical compositions comprising combinations of a GABA agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and an ARI, a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. Excerpt(s): The present application is a U.S. non-provisional application. This application claims the benefit of U.S. No. 60/250,448 filed on Nov. 30, 2000, under 35 USC 119(e). This invention relates to pharmaceutical combinations of a.gamma.aminobutyric acid (GABA) agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from diabetic complications such as, inter alia, diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. This invention also relates to additive and synergistic combinations of a GABA agonist, a prodrug thereof or a pharmaceutically acceptable salt of said GABA agonist or said prodrug and an ARI, a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug, whereby those additive and synergistic combinations are useful in treating mammals, including humans, suffering from diabetic complications such as, inter alia, diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic
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retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. GABA is the major inhibitory neurotransmitter in the mammalian central nervous system. Its receptors have been divided into two main types. The more prominent GABA receptor subtype, the GABA.sub.A receptor, is a ligand-gated Cl.sup.ion channel that is opened after release of GABA from presynaptic neurons. A second receptor, the GABA.sub.B receptor, is a member of the G protein-coupled receptor family coupled both to biochemical pathways and to regulation of ion channels. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, New York, N.Y., 9.sup.th Edition, (1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and treatment for diabetic complications Inventor(s): Mylari, Banavara L.; (Waterford, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020061918 Date filed: October 31, 2001 Abstract: This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective COX-2 inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said selective COX-2 inhibitor or said prodrug. This invention further relates to methods of using those pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy and diabetic cardiomyopathy. Excerpt(s): This invention relates to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective cyclooxygenase-2 (COX-2) inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said selective COX2 inhibitor or said prodrug. This invention further relates to methods of using such pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, myocardial infarction, cataracts and diabetic cardiomyopathy. Aldose reductase inhibitors function by inhibiting the activity of the enzyme aldose reductase, which is primarily responsible for regulating the reduction of aldoses, such as glucose and galactose, to the corresponding polyols, such as sorbitol and galactitol, in humans and other animals. In this way, unwanted accumulations of galactitol in the lens of galactosemic subjects and of sorbitol in the lens, peripheral nervous cord and kidneys of various diabetic subjects are prevented or reduced. Accordingly, aldose reductase inhibitors are of therapeutic value for controlling certain diabetic complications, e.g., diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, myocardial infarction, cataracts and diabetic retinopathy. Two forms of cylcooxygenase (COX) are known to exist: COX-1 and COX-2, the former being a constitutive form and the latter being an inducible form. COX-1 exists in the stomach, intestines, kidneys and platelets while COX-2 is expressed during inflammation. Both COX enzyme isoforms metabolize arachidonic by a similar mechanism, but each have different substrate specificities. Selective COX-2 inhibitors are advantageous in the treatment of pain and inflammation while avoiding such side effects as gastric and renal toxicity.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Focused compression mitral valve device and method Inventor(s): Adams, John M.; (Sammamish, WA), Mathis, Mark L.; (Kirkland, WA), Reuter, David G.; (Bothell, WA), Wolf, Scott J.; (Bellevue, WA) Correspondence: Richard O. Gray, JR.; Graybeal Jackson Haley Llp; Suite 350; 155-108th Avenue NE; Bellevue; WA; 98004-5901; US Patent Application Number: 20030083538 Date filed: November 1, 2001 Abstract: A mitral valve therapy device and method treats dilated cardiomyopathy. The device is configured to be placed in the coronary sinus of a heart adjacent to the mitral valve annulus. The device includes a force distributor that distributes an applied force along a pericardial wall of the coronary sinus, and a force applier that applies the applied force to one or more discrete portions of a wall of the coronary sinus adjacent to the mitral valve annulus to reshape the mitral valve annulus in a localized manner. Excerpt(s): The present invention generally relates to a device and method for treating dilated cardiomyopathy of a heart. The present invention more particularly relates to a device and method for delivering a localized force to the mitral valve annulus to reshape the mitral valve annulus. The human heart generally includes four valves. Of these valves, a most critical one is known as the mitral valve. The mitral valve is located in the left atrial ventricular opening between the left atrium and left ventricle. The mitral valve is intended to prevent regurgitation of blood from the left ventricle into the left atrium when the left ventricle contracts. In preventing blood regurgitation the mitral valve must be able to withstand considerable back pressure as the left ventricle contracts. The valve cusps of the mitral valve are anchored to muscular wall of the heart by delicate but strong fibrous cords in order to support the cusps during left ventricular contraction. In a healthy mitral valve, the geometry of the mitral valve ensures that the cusps overlie each other to preclude regurgitation of the blood during left ventricular contraction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Isoform-selective inhibitors phosphodiesterases
and
activators
of
PDE3
cyclic
nucleotide
Inventor(s): Movsesian, Matthew A.; (Salt Lake City, UT) Correspondence: Richard A. Nakashima; Blakely, Sokoloff, Taylor & Zafman Llp; Seventh Floor; 12400 Wilshire Boulevard; Los Angeles; CA; 90025-1030; US Patent Application Number: 20030158133 Date filed: June 19, 2002 Abstract: The present invention concerns methods and compositions related to type 3 phosphodiesterases (PDE3). Certain embodiments concern isolated peptides corresponding to various PDE3A isoforms and/or site-specific mutants of PDE3A isoforms, along with expression vectors encoding such isoforms or mutants. In specific embodiments, methods for identifying isoform selective inhibitors or activators of PDE3 are provided, along with methods of use of such inhibitors or activators in the treatment
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of dilated cardiomyopathy, pulmonary hypertension and/or other medical conditions related to PDE3 effects on cAMP levels in different intracellular compartments. Excerpt(s): The present invention relates to the field of cardiovascular and other diseases. More particularly, the present invention concerns compositions and methods of identification and use of isoform selective activators or inhibitors of type 3 phosphodiesterase (PDE3). Other embodiments of the invention concern highthroughput screening for novel pharmaceuticals directed against PDE3 isoforms. In certain embodiments, the compositions and methods disclosed herein are of use for treatment of cardiomyopathy, pulmonary hypertension and related conditions. PDE3 cyclic nucleotide phosphodiesterases hydrolyze cAMP and cGMP and thereby modulate cAMP- and cGMP-mediated signal transduction (Shakur et al., 2000a). These enzymes have a major role in the regulation of contraction and relaxation in cardiac and vascular myocytes. PDE3 inhibitors, which raise intracellular cAMP and cGMP content, have inotropic effects attributable to the activation of cAMP-dependent protein kinase (PK-A) in cardiac myocytes and vasodilatory effects attributable to the activation of cGMPdependent protein kinase (PK-G) in vascular myocytes (Shakur et al., 2000a). When used in the treatment of dilated cardiomyopathy, PDE3 inhibitors such as milrinone, enoximone and amrinone initially elicit favorable haemodynamic responses, but longterm administration increases mortality by up to 40% (Nony et al., 1994). This linkage of short-term benefits of PDE3 inhibition to deleterious effects on long-term survival in dilated cardiomyopathy is one of the most perplexing problems in cardiovascular therapeutics. However, it is thought that these biphasic effects reflect the compartmentally-nonselect- ive increases in intracellular cAMP content in cardiac myocytes current inhibitors display. Clinical trials of the use of.beta.-adrenergic receptor agonists--which, like PDE3 inhibitors, increase intracellular cAMP content in cardiac myocytes--were terminated prior to completion because of increased mortality in treated patients, while.beta.-adrenergic receptor antagonists, which reduce intracellular cAMP content, have been shown to improve long-term survival despite initially adverse haemodynamic effects. These findings suggest that both the short-term benefits and long-term adverse effects of PDE3 inhibition are attributable to increases in intracellular cAMP content in cardiac myocytes (Movsesian, 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
METHOD FOR DETECTING DISEASE-ASSOCIATED MUTATIONS Inventor(s): SEIDMAN, JOHN; (MILTON, MA), WATKINS, HUGH; (BROOKLINE, MA), ROSENZWEIG, ANTHONY; (NEWTON, MA), SEIDMAN, CHRISTINE; (MILTON, MA) Correspondence: Elizabeth A Hanley; Lahive And Cockfield; 28 State Street; Boston; MA; 02109 Patent Application Number: 20030054343 Date filed: June 6, 1995 Abstract: A method is described for diagnosing individuals as having hypertrophic cardiomyopathy, e.g. familial or sporadic hypertrophic cardiomyopathy. The method provides a useful diagnostic tool which becomes particularly important when testing asymptomatic individuals suspected of having the disease. Symptomatic individuals have a much better chance of being diagnosed properly by a physician. Asymptomatic individuals from families having a history of familial hypertrophic cardiomyopathy may be selectively screened using the method of this invention allowing for a diagnosis
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prior to the appearance of any symptoms. Individuals having the mutation responsible for the disease may be counseled to take steps which hopefully would prolong their life, i.e. avoid rigorous exercise. The methodology used in the above method also has broad applicability and may be used to detect other disease-associated mutations in DNA obtained from subjects being tested for other disease-associated mutations. Excerpt(s): The use of an individual's genetic information in the diagnosis of a disease is becoming more prevalent. Many diseases are caused by a defect in a single gene of an individual. All known autosomal dominant, autosomal recessive and X-linked disorders are believed to be caused by a defect in a single gene (Antonarakis, New England Journal of Medicine Vol. 320, No. 3:153-63 (1981)). Genes responsible for some diseases or disorders have been cloned and characterized. The defect in the gene may be a gross gene alteration, a small gene alteration or even a point mutation. Examples of some diseases caused by a mutation in a gene include Gaucher's disease, hemophelia A and B, Duchenne's muscular dystrophy, sickle cell anemia, Tay-Sachs disease, phenylketonoria and cystic fibrosis. Familial hypertrophic cardiomyopathy (hereinafter FHC) has been linked to mutations in the.beta. cardiac myosin heavy-chain gene (Tanigawa et al., Cell 62:991-998 (1990)); Geisterfer-Lowrance et al., Cell 61:999-1006 (1990)). Tanigawa et al. studied a single family (Family B) and hypothesized that the FHC in this family was due to a mutation that results in the formation of an.alpha./.beta. cardiac myosin heavychain hybrid gene. Geisterfer-Lowrance et al. also studied a single family and hypothesized that a missense mutation in the.beta. cardiac myosin heavy-chain gene caused FHC in the family studied. FHC is a well characterized autosomal dominant disorder or disease. It is autosomal dominant in that fifty percent of the children of affected parents eventually become afflicted with the disease. FHC is characterized by unexplained myocardial hypertrophy. The clinical symptoms of individuals having FHC are variable and some individuals do not have any symptoms. The symptoms of FHC include dypsnea, angina, ischemia. Pathological findings of the disease include increased myocardial mass with myocyte and myofibrillar disarray. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treatment and pharmaceutical composition Inventor(s): Gasparo, Marc de; (Es Planches, CH), Webb, Randy Lee; (Flemington, NJ) Correspondence: Thomas Hoxie; Novartis Corporation; Patent And Trademark Dept; 564 Morris Avenue; Summit; NJ; 079011027 Patent Application Number: 20010049384 Date filed: January 9, 2001 Abstract: The invention relates to a method for the treatment or prevention of a condition or disease selected from the group consisting of hypertension, (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, myocardial infarction and its sequelae, supraventricular and ventricular arrhythmias, atrial fibrillation or atrial flutter, atherosclerosis, angina (whether stable or ustable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetessecondary aldosteronism, primary and secondary pulmonary hyperaldosteronism, primary and pulmonary hypertension, renal failure conditions, such as diabetic nephropathy,glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, Raynaud's disease, luminal hyperplasia, cognitive dysfunction (such as Alzheimer's), and stroke,
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comprising administering a therapeutically effective amount of combination of (i) the AT.sub.1-antagonists valsartan or a pharmaceutically acceptable salt thereof and (ii) a Calcium channel blocker or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier to a mammal in need of such treatment and to corresponding pharmaceutical combination composition. Excerpt(s): (iii) a pharmaceutically acceptable carrier. Valsartan is disclosed in EP 0443983 A. A CCB useful in said combination is preferably selected from the group consisting of amlodipine, diltiazem, felodipine, fendiline, flunarizine, gallopamil, isradipine, lacidipine, mibefradil, nicardipine, nifedipine, niguldipine, niludipine, nimodipine, nisoldipine, nitrendipine, nivaldipine, ryosidine, tiapamil and verapamil, and in each case, a pharmaceutically acceptable salt thereof. All these drugs are therapeutically used as CCBs, e.g. as anti-hypertensive, anti-angina pectoris or antiarrhythmic drugs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compositions relating to MEK5 and cardiac hypertrophy and dilated cardiomyopathy Inventor(s): Nicol, Rebekka; (Hicksville, NY), Olson, Eric N.; (Dallas, TX) Correspondence: Steven L. Highlander; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue,; Austin; TX; 78701-3271; US Patent Application Number: 20030144176 Date filed: May 30, 2002 Abstract: The present invention relates to compositions and methods relating to MEK5 and its role in heart disease. This protein has now been identified as a target for therapeutic intervention due to its role molecular events that lead to or contribute to cardiac hypertrophy and/or dilated cardiomyopathy. In particular, inhibition of MEK5 activity will lead to decrease signalling of the pathways and reduce or eliminate the effects on sarcomere assembly, which in turn result or contribute to cardiac dysfunction. Also provided are transgenic animals and methods of screening for inhibitors of MEK5. Excerpt(s): This application claims benefit of priority to U.S. Provisional Application Serial No. 60/295,875, filed Jun. 4, 2001, the entire content of which is hereby incorporated by reference. The present invention relates generally to the fields of developmental biology and molecular biology. More particularly, it concerns gene regulation and cellular physiology in cardiomyocytes. Cardiac cells do not divide after birth, so both normal growth of the myocardium as well as stress-induced myocardial remodeling must take place through hypertrophic growth without cell division (MacLellan and Schneider, 2000). Cardiac hypertrophy can occur by an increase in width of myofibrils, resulting in a thickening of the myocardial wall or "concentric hypertrophy," or by an increase in myofibril length, producing chamber dilation or "eccentric hypertrophy." These contrasting forms of hypertrophy are coupled to parallel versus serial assembly of sarcomeres, respectively. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions relating to muscle specific sarcomeric calcineurin-binding proteins (calsarcins) Inventor(s): Frey, Norbert; (Dallas, TX), Olson, Eric; (Dallas, TX) Correspondence: Steven L. Highlander; Fulbright & Jaworski L.L.P.; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030078376 Date filed: November 7, 2001 Abstract: The present invention relates to the polypeptides known as calcineurin associated protein (calsarcin). Calsarcins-1, -2, and -3 bind to calcineurin, telethonin, and.alpha.-actinin, which provides a link between these molecules and the sarcomere. Sarcomeric dysfunction ultimately leads to activation of calcineurin and consequent hypertrophic cardiomyopathy. Thus, methods utilizing calsarcin as it regards these medical conditions are herein provided and include screening for peptides which interact with calsarcin, screening for modulators of calsarcin binding to calcineurin or.alpha.-actinin, methods to modulate calcineurin activity, methods to inhibit calcineurin activation of gene transcription and methods for treating cardiac hypertrophy, heart failure and Type II diabetes. Excerpt(s): The present application claims priority to co-pending U.S Provisional Patent Application Serial No. 60/246,629 filed on Nov. 7.sup.th, 2000. The entire text of the above-referenced disclosure is specifically incorporated herein by reference without disclaimer. The government may own rights in the present invention pursuant to grant number HL53351-06 from the National Institutes of Health. The present invention relates generally to the fields of cell biology and molecular biology. Particularly, it concerns the regulation of activity of calcineurin through a calcineurin-associated sarcomeric protein (calsarcin). More particularly, it concerns the regulation of activity of calcineurin through CALSARCIN-1, which also interacts with the sarcomererelated.alpha.-actinin. Calcineurin is a serine/threonine protein phosphatase that plays a pivotal role in developmental and homeostatic regulation of a wide variety of cell types (Klee et al., 1998; Crabtree, 1999). The interaction of calcineurin with transcription factors of the NFAT family following activation of the T cell receptor in leukocytes provides the best characterized example of how calcineurin regulates gene expression (Rao et al., 1997). Changes in intracellular calcium promote binding of Ca.sup.2+/calmodulin to the catalytic subunit of calcineurin (CnA), thereby displacing an autoinhibitory region and allowing access of protein substrates to the catalytic domain. Dephosphorylation of NFAT by activated calcineurin promotes its translocation from the cytoplasm to the nucleus, where NFAT binds DNA cooperatively with an AP 1 heterodimer to activate transcription of genes encoding cytokines, such as IL-2. This basic model of NFAT activation has been shown to transduce Ca.sup.2+ signals via calcineurin in many cell types and to control transcription of diverse sets of target genes unique to each cellular environment (Timmerman et al., 1996). In each case, NFAT acts cooperatively with other transcription factors that include proteins of the AP1 (Rao et al., 1997), cMAF (Ho et al., 1996), GATA (Mesaeli et al., 1999; Molkentin et al., 1998; Musaro et al., 1999), or MEF2 (Chin et al., 1998; Liu et al., 1997; Mao et al., 1999; Mao and Wiedmann, 1999) families. In addition to T cell activation, cellular responses controlled by calcineurin signaling include synaptic plasticity (Mao et al., 1999, Graef et al., 1999; Zhuo et al., 1999) and apoptosis (Wang et al., 1999; Youn et al., 1999). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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METHODS FOR DETECTING MUTATIONS HYPERTROPHIC CARDIOMYOPATHY
ASSOCIATED
WITH
Inventor(s): MCRAE, CALUM; (BROOKLINE, MA), SEIDMAN, JONATHAN; (MILTON, MA), SIEDMAN, CHRISTINE; (MILTON, MA), THIERFELDER, LUDWIG; (BERLIN, DE), WATKINS, HUGH; (HEADINGTON, GB) Correspondence: Lahive & Cockfield, Llp; 28 State Street; Boston; MA; 02109 Patent Application Number: 20020127548 Date filed: November 30, 1995 Abstract: The invention pertains to methods for detecting the presence or absence of a mutation associated with hypertrophic cardiomyopathy (HC). The methods include providing DNA which encodes a cardiac myosin binding protein and detecting the presence or absence of a mutation in the amplified product which is associated with HC. The invention further pertains to methods for diagnosing HC in a subject. These methods typically include obtaining a sample of DNA which encodes a cardiac myosin binding protein from a subject being tested for FHC and diagnosing the subject for FHC by detecting the presence or absence of a mutation in the sarcomeric thin filament protein which causes FHC as an indication of the disease. Other aspects of the invention include kits useful for diagnosing HC and methods for treating HC. Excerpt(s): This application is a continuation-in-part application of Ser. No. 08/354,326 filed on Dec. 12, 1994, now pending, which is a continuation of Ser. No. 08/252,627 filed on Jun. 2, 1994, which is a continuation-in-part application of Ser. No. 07/989,160, filed Dec. 11, 1992, now issued U.S. Pat. No. 5,429,923. The contents of all of the aforementioned applications and/or issued patent are expressly incorporated herein by reference. Familial hypertrophic cardiomyopathy (hereinafter FHC) is a primary and inherited disorder of heart muscle that is characterized by increased ventricular mass, hyperkinetic systolic function and impaired diastolic relaxation. Goodwin, J. F. et al. (1961) Br. Med J 21:69-79. The pathological features of this disorder are well established (Maron, B. J. and Epstein, S. E. (1980) Amer. J. Cardiol 45:141-154). In addition to the classical finding of asymmetrical thickening of the intraventricular septum, hypertrophy of the adjacent left ventricular anterior free wall, apex or right ventricle can also occur. Hence the anatomical distribution and severity of hypertrophy can vary considerably. Maron, B. J. et al. (1981) Amer. J. Cardiol. 48:418-428. Fibrosis occurs within the hypertrophied ventricle and a fibrotic plaque is frequently demonstrable over the septal region that apposes the anterior mitral valve leaflet during systole. Other gross pathological findings include atrial dilation and thickening of the mitral valve leaflets. Roberts, W. C. and Ferrans, V. J. (1975) Hum Pathol. 6:287-342. The most characteristic histological abnormalities seen in FHC are in myocyte and myofibrillar disarray. Davies, M. J. (1984) Br. Heart. J. 51:331-336. Myocytes can be hypertrophied to ten to twenty times the diameter of a normal cardiac cell and may contain hyperchromatic, bizarre nuclei. Becker, A. E. (1989) Pathology of Cardiomyopathies in Cariomyopathies: Clinical Presentation, Differential Diagnosis, and Management (Shaver. J. A. ed.) F. A. Davis Co., New York, pp. 9-31. Cells are arranged in a disorganized fashion with abnormal bridging of adjacent muscle fibers and intercellular contacts, producing whorls. Ultrastructural organization is also distorted: myofibrils and myofilaments are disoriented with irregular Z bands. Ferrans, V. J. et al. (1972) Circulation 45:769-792. While the histopathological features overlap Keith those seen in hypertrophy that is secondary to other diseases, the extent of ventricular involvement and the severity of myocyte and myofibrillar disarray are considerably greater in FHC.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treating diabetic cardiomyopathy using glycogen phosphorylase inhibitors Inventor(s): Treadway, Judith L.; (Mystic, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20010046958 Date filed: January 23, 2001 Abstract: The present invention provides methods of treating diabetic cardiomyopathy, the methods comprising administering to a patient having or at risk of having diabetic cardiomyopathy a therapeutically effective amount of a glycogen phosphorylase inhibitor. The present invention also provides methods of treating diabetic cardiomyopathy, the methods comprising administering to a patient having 1) diabetes and 2) having cardiovascular disease, ischemic heart disease, congestive heart failure, congestive heart failure but not having coronary arteriosclerosis, hypertension, diastolic blood pressure abnormalities, microvascular diabetic complications, abnormal left ventricular function, myocardial fibrosis, abnormal cardiac function, pulmonary congestion, small vessel disease, small vessel disease without atherosclerotic cardiovascular disease or luminal narrowing, coagulopathy, cardiac contusion, or having had or at risk of having a myocardial infarction a therapeutically effective amount of a glycogen phosphorylase inhibitor. Excerpt(s): This application claims priority of U.S. application Ser. No. 60/177,770, filed Jan. 24, 2000. The present invention relates to methods of treating diabetic cardiomyopathy, the methods comprising administering to a patient having or at risk of having diabetic cardiomyopathy a therapeutically effective amount of a glycogen phosphorylase inhibitor. The present invention also relates to methods of treating diabetic cardiomyopathy, the methods comprising administering to a patient having 1) diabetes and 2) having cardiovascular disease, ischemic heart disease, congestive heart failure, congestive heart failure but not having coronary arteriosclerosis, hypertension, diastolic blood pressure abnormalities, microvascular diabetic complications, abnormal left ventricular function, myocardial fibrosis, abnormal cardiac function, pulmonary congestion, small vessel disease, small vessel disease without atherosclerotic cardiovascular disease or luminal narrowing, coagulopathy, cardiac contusion, or having had or at risk of having a myocardial infarction a therapeutically effective amount of a glycogen phosphorylase inhibitor. Diabetic cardiomyopathy, a disease of the heart muscle (myocardium), is considered a distinct medical entity from either diabetes or cardiovascular disease. Diabetic cardiomyopathy occurs in patients having insulin dependent diabetes mellitus (Type 1) and in patients having non-insulin dependent diabetes mellitus (Type 2). Diabetic cardiomyopathy clinically expresses itself as congestive heart failure (CHF) and left ventricular hypertrophy. Diabetic cardiomyopathy is also associated with increased morbidity and mortality. Pathologically, diabetic cardiomyopathy is characterized by myocellular hypertrophy, interstitial fibrosis, increased myocardial lipid deposition, and varying degrees of small vessel disease. Diabetic cardiomyopathy differs from ischemic cardiomyopathy because the diseased myocardium and resultant CHF can occur in the absence of frank coronary atherosclerosis or luminal narrowing. This suggests that the primary metabolic defects related to hyperglycemia that exist in the myocardial tissue and/or in the coronary
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microcirculation itself are responsible for the diseased state and loss of myocardial function in diabetics. Co-existent hypertension, microvascular complications, impaired fibrinolysis, atherosclerotic cardiovascular disease, and/or myocardial ischemia, which frequently occur in diabetic patients, compound the severity of the underlying diabetic cardiomyopathy. These co-morbidities can lower the threshold for decompensated heart failure, pulmonary edema, and arrhythmias, which can result in the death of the patient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treatment and pharmaceutical composition Inventor(s): Ksander, Gary Michael; (Amherst, NH), Webb, Randy Lee; (Flemington, NJ) Correspondence: Thomas Hoxie; Novartis, Corporate Intellectual Property; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030144215 Date filed: January 14, 2003 Abstract: The invention relates a pharmaceutical composition comprising a combination of:(i) the AT 1-antagonist valsartan or a pharmaceutically acceptable salt thereof; and(ii) a NEP inhibitor or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable carrier and to a method for the treatment or prevention of a condition or diseaseselected from the group consisting of hypertension, heart failure, such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction, such as Alzheimer's, glaucoma and stroke, comprising administering a therapeutically effective amount of the pharmaceutical composition to a mammal in need thereof. Excerpt(s): The renin angiotensin system is a complex hormonal system comprised of a large molecular weight precursor, angiotensinogen, two processing enzymes, renin and angiotensin converting enzyme (ACE), and the vasoactive mediator angiotensin II (Ang II). See J. Cardiovasc. Pharmacol., Vol. 15, Suppl. B, pp. S1-S5 (1990). The enzyme renin catalyzes the cleavage of angiotensinogen into the decapeptide angiotensin I, which has minimal biological activity on its own and is converted into the active octapeptide Ang II by ACE. Ang II has multiple biological actions on the cardiovascular system, including vasoconstriction, activation of the sympathetic nervous system, stimulation of aldosterone production, anti-natriuresis, stimulation of vascular growth and stimulation of cardiac growth. Ang II functions as a pressor hormone and is involved the pathophysiology of several forms of hypertension. The vasoconstrictive effects of angiotensin II are produced by its action on the non-striated smooth muscle cells, the stimulation of the formation of the adrenergenic hormones epinephrine and norepinephrine, as well as the increase of the activity of the sympathetic nervous system as a result of the formation of norepinephrine. Ang II also has an influence on electrolyte balance, produces, e.g., anti-natriuretic and anti-diuretic effects in the kidney and
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thereby promotes the release of, on the one hand, the vasopressin peptide from the pituitary gland and, on the other hand, of aldosterone from the adrenal glomerulosa. All these influences play an important part in the regulation of blood pressure, in increasing both circulating volume and peripheral resistance. Ang II is also involved in cell growth and migration and in extracellular matrix formation. Ang II interacts with specific receptors on the surface of the target cell. It has been possible to identify receptor subtypes that are termed, e.g., AT 1- and AT 2-receptors. In recent times great efforts have been made to identify substances that bind to the AT 1-receptor. Such active ingredients are often termed Ang II antagonists. Because of the inhibition of the AT 1receptor such antagonists can be used, e.g., as anti-hypertensives or for the treatment of congestive heart failure, among other indications. Ang II antagonists are therefore understood to be those active ingredients which bind to the AT 1-receptor subtype. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multi-electrode apparatus and method for treatment of congestive heart failure Inventor(s): Mathis, Scott; (Durango, CO), Prentice, John K.; (Durango, CO), Rottenberg, William B.; (Durango, CO), Schmidt, John A.; (Durango, CO) Correspondence: Gottlieb Rackman & Reisman PC; 270 Madison Avenue; 8th Floor; New York; NY; 100160601 Patent Application Number: 20020169484 Date filed: February 13, 2002 Abstract: An apparatus and method for treatment of congestive heart failure from the right side of the heart. An implantable cardiac stimulation system with a multi-electrode lead having three or more selectable electrodes, together with apparatus for identifying an optimal subset of electrodes, apparatus for shaping a propagating wave front, and apparatus for modifying the intrinsic ventricular cardiac activation sequence, or generating simultaneous or near simultaneous pacing pulses to the septum or right ventricular outflow tract during ventricular systole in order to improve left ventricular cardiac efficiency and reduce mitral regurgitation in patients with dilated cardiomyopathy. A three dimensional map of electrode placement may be calculated. A sub set of the available electrodes in the right side of the heart is selected for stimulation such that septal motion during systole is reduced or the mitral valve area is stiffened to reduce mitral regurgitation. Excerpt(s): This invention pertains to a method and apparatus for applying cardiac stimulation using multiple electrodes, and more particularly, to a method and apparatus for treatment of congestive heart failure. The heart is a mechanical pump that is stimulated by electrical impulses. The mechanical action of the heart results in the flow of blood. During a normal heartbeat, the right atrium (RA) fills with blood from the returning veins. The RA then contracts and this blood is moved into the right ventricle (RV). When the RV contracts it pumps that blood to the lungs. Blood returning from the lungs moves into the left atrium (LA), and after LA contraction, is pumped into the left ventricle (LV), which then pumps it throughout the body. Four heart valves keep the blood flowing in the proper directions. The electrical signal that drives this mechanical contraction starts in the sino-atrial node, a collection of specialized heart cells in the right atrium that automatically depolarize (change their voltage potential). This depolarization wave front passes across all the cells of both atria and results in atrial contraction. When the advancing wave front reaches the A-V node it is delayed so that the contracting atria have time to fill the ventricles. The depolarizing wave front then
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passes over the ventricles, causing them to contract and pump blood to the lungs and body. This electrical activity occurs approximately 72 times a minute in a normal individual and is called normal sinus rhythm. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nlk1 protein and Nlk1 protein complexes Inventor(s): Nandabalan, Krishnan; (Guilford, CT), Schulz, Vincent P.; (Madison, CT), Yang, Meija; (East Lyme, CT) Correspondence: Mintz, Levin, Cohn, Ferris,; Glovsky And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030087412 Date filed: September 13, 2002 Abstract: Disclosed are complexes of the NlK1 protein and proteins identified as interacting with the NlK1 protein (NlK1 protein-IPs). The NlK-1 interacting proteins include TrkA, protein phosphatase 1.alpha., 14-3-3.epsilon.,.alpha.-tropomyosin, vimentin, p0071, Ini-1, and newly described proteins named IP-1, IP-2, IP-3, IP-4, and IP5. Also described are derivatives, fragments analogs and homologs of these proteins. Methods of screening these complexes for efficacy in treating and/or preventing various diseases and disorders, particularly, neoplasia, neurodegenerative disease, hypertrophic cardiomyopathy, viral infections and metabolic diseases and disorders are also disclosed. Excerpt(s): The present invention disclosed herein relates to complexes of the Nlk1 protein with other proteins, in particular, complexes of the Nlk1 protein with the following proteins: TrkA, protein phosphatase-1.alpha., 14-3-3.epsilon.,.alpha.tropomyosin, vimentin, p0071, Ini-1, IP-1 (an intermediate filament associated protein), IP-2 (a tropomyosin homolog protein), IP-3 (a ubiquitin hydroxylase homolog protein), IP-4 (a collagen homolog protein) and IP-5 (a tropomyosin homolog protein). In addition, the present invention relates to the production of antibodies to the aforementioned Nlk1 protein complexes, and their use in, inter alia, screening, diagnosis, prognosis and therapy. The present invention further relates to the IP-1, IP-3, IP-4, and IP-5 genes and proteins, as well as derivatives, fragments, analogs and homologs, thereof. It is a well-established tenet in molecular biology that loss of control of cell proliferation may lead to severe diseases and disorders (e.g., neoplasia). Hence, the elucidation of the intricacies of the cell-cycle, and its deregulation during oncogenesis, will provide novel opportunities in the prophylactic, diagnostic and therapeutic management of cancer and other proliferation-related diseases. A better understanding of the cell-cycle could be achieved by the elucidation of the interactions of the various protein complexes, whose levels and biological activities are regulated through the cell-cycle. The identification and classification of these protein complexes will be useful in the development of treatment modalities and assays for various pathological processes including, but not limited to, hyperproliferative disorders (e.g., tumorigenesis and tumor progression), as well as other related genetic disorders. It should be noted that the citation of a reference herein should not be construed as an admission that such is prior art to the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel triazine compounds useful as sorbitol dehydrogenase inhibitors Inventor(s): Mylari, Banavara L.; (Waterford, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030004166 Date filed: March 26, 2002 Abstract: This invention is directed to sorbitol dehydrogenase inhibitory compounds of formula I 1wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in the specification. This invention is also directed to pharmaceutical compositions containing these compounds which inhibit sorbitol dehydrogenase and to methods of treating or preventing diabetic complications, particularly diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, diabetic macroangiopathy, diabetic cardiomyopathy and foot ulcers, by administering such compounds to a mammal suffering from diabetes and therefore at risk for developing such complications. This invention is also directed to pharmaceutical compositions comprising a combination of a compound of formula I of the present invention with a second pharmaceutical agent, including an aldose reductase inhibitor, a sodium hydrogen ion exchange (NHE-1) inhibitor, a glycogen phosphorylase inhibitor (GPI), a selective serotonin reuptake inhibitor, a 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitor, an angiotensin converting enzyme inhibitor, a thiazolidinedione antidiabetic agent, an angiotensin 11 receptor antagonist, a.gamma.-aminobutyric acid (GABA) agonist, a phosphodiesterase type 5 inhibitor, an adenosine agonist, and a CETP inhibitor and to methods of using these combination compositions. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/280,050, filed Mar. 30, 2001. The present invention relates to novel triazine compounds of formula I, isomers thereof, prodrugs of said compounds or isomers, or pharmaceutically acceptable salts of said compounds, isomers or prodrugs, and to methods of using such compounds to inhibit sorbitol dehydrogenase (SDH), lower fructose levels or treat diabetic complications, such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy, in mammals. The present invention also relates to pharmaceutical compositions containing such triazine compounds. The present invention also relates to pharmaceutical compositions and kits comprising a combination of a sorbitol dehydrogenase inhibitor of formula I, an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug, and a second pharmaceutical agent and to methods of using these combination compositions and kits. Triazine compounds of formula I, as defined below, and their pharmaceutically acceptable salts, lower fructose levels in the tissues of mammals affected by diabetes (e.g., nerve, kidney and retina tissue) and are useful in the treatment and prevention of the diabetic complications referred to above. These compounds, and/or their metabolites in vivo, are inhibitors of the enzyme sorbitol dehydrogenase, which catalyzes the oxidation of sorbitol to fructose. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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p53 binding protein-related protein in cardiomyopathy Inventor(s): Beier, David R.; (Brookline, MA), Herron, Bruce; (Nassau, NY), Rao, Cherie; (Oceanside, CA) Correspondence: Michael A. Sanzo; Fitch, Even, Tabin & Flannery; Suite 401l; 1801 K Street, N.W.; Washington; DC; 20006-1201; US Patent Application Number: 20030031680 Date filed: June 14, 2002 Abstract: The present invention is directed to a mouse model of dilated cardiomyopathy in which animals are deficient in the expression of a gene encoding a p53 binding protein-related protein (PRP). The invention also encompasses the mouse PRP gene and protein themselves as well as counterparts found in the human. The various genes and proteins can be used in making transgenic animals and in assays designed to determine the likelihood of an individual developing cardiomyopathy. Excerpt(s): The present application claims the benefit of U.S. provisional application No. 60/299,160, filed on Jun. 20, 2001. The present invention is directed to a mouse model of dilated cardiomyopathy. It also includes genes and proteins whose underexpression contributes to disease development and a variety of compositions and methods in which these genes and proteins are used. Congestive heart failure affects over 4 million people in the United States and is the most common cause of hospitalization for patients over the age of 65. A leading cause of congestive heart failure is dilated cardiomyopathy. This condition is characterized by the progressive expansion of the heart muscle and an accompanying inability to maintain adequate blood flow. Patients typically complain of fatigue, shortness of breath and chest pain. There is presently no cure for this condition and up to 50% of patients die or require a heart transplant within 5 years of diagnosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pathogenesis of cardiomyopathy Inventor(s): Campbell, Kevin P.; (Iowa City, IA), Cohn, Ronald; (Iowa City, IA), Coral, Ramon; (Iowa City, IA), Durbeej, Madeleine; (Iowa City, IA), Williamson, Roger; (Iowa City, IA) Correspondence: Farrell & Associates, P.C.; P.O. Box 999; York Harbor; ME; 03911; US Patent Application Number: 20010016952 Date filed: January 4, 2001 Abstract: Disclosed within is a mouse, and cells derived therefrom, which are homozygous for a disrupted.delta.-sarcoglycan gene, the disruption in said gene having been introduced into the mouse or an ancestor of the mouse at an embryonic stage. Said disruption prevents the synthesis of functional.delta.-sarcoglycan in cells of the mouse and results in the mouse having a reduced amount of.beta.- and.epsilon.-sarcoglycan and sarcospan, and a disruption of the sarcoglycan-sarcospan complex in smooth muscle of the mouse. Said disruption also results in a reduced amount of sarcospan,.alpha.-,.beta.-,.gamma.-, and.epsilon.-sarcoglycan in the sarcolemma of skeletal and cardiac muscles of the mouse, compared to the amounts of said components in a mouse lacking disrupted.delta.-sarcoglycan genes. Preferred specific disruptions of the.delta.-sarcoglycan gene are listed. Also disclosed is a mouse, and cells derived therefrom, which are homozygous for a disrupted.beta.-sarcoglycan gene, the
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disruption in said gene having been introduced into the mouse or an ancestor of the mouse at an embryonic stage. The disruption prevents the synthesis of functional.beta.sarcoglycan in cells of the mouse and results in the mouse having a reduced amount of.delta.- and.epsilon.-sarcoglycan and sarcospan and.alpha.-dystroglycan in smooth muscle of the mouse. The disruption also results in a disruption of the sarcoglycansarcospan complex in smooth muscle of the mouse, and a reduced amount of sarcospan,.alpha.,.gamma.,.delta.- and.epsilon.-sarcoglycan in the sarcolemma of skeletal and cardiac muscles of the mouse, compared to the amounts of the components in a mouse lacking disrupted.beta.-sarcoglycan genes. Preferred specific disruptions of the.beta.-sarcoglycan gene are listed. A method for treating mammalian autosomal recessive limb-girdle muscular dystrophy type 2F in an individual is also disclosed. The method comprises, providing an expression vector which encodes a wild-type form of.delta.-sarcoglycan, and introducing the expression vector into skeletal and smooth muscle tissue of the individual under conditions appropriate for expression of the wildtype form of.delta.-sarcoglycan in said tissues. Examples of expression vectors for use in this method are adenovirus expression vector, a gutted adenovirus expression vector, and an adeno-associated expression vector. Also disclosed are methods for treating mammalian autosomal recessive limb-girdle muscular dystrophy type 2E, and type 2F, in an individual. The methods comprise, providing an expression vector which encodes a wild-type form of.beta.-sarcoglycan, or.delta.-sarcoglycan, respectively, and introducing the expression vector into skeletal and smooth muscle tissue of the individual under conditions appropriate for expression of the wild-type form of the sarcoglycan gene in said tissues. The.delta.-sarcoglycan deficient, and.beta.-sarcoglycan deficient mice of the present invention are useful in identifying therapeutic compounds for treatment of an individual diagnosed with.delta.-sarcoglycan-deficient limb-girdle muscular dystrophy, and.beta.-sarcoglycan-deficient limb-girdle muscular dystrophy, respectively. A therapeutic method for treating ischemic heart disease caused by reduced expression of the sarcoglycan-sarcospan complex in vascular smooth muscle cells of an individual is also provided. The method comprises contacting the vascular smooth muscle cells of the individual with a vascular smooth muscle relaxant, such as Nicorandil. This method is also useful for preventing ischemic injury in skeletal and cardiac muscle of an individual caused by reduced expression of the sarcoglycansarcospan complex in the vascular smooth muscle cells of the individual. The method is also useful for treating mammalian autosomal recessive limb-girdle muscular dystrophy type 2F or type 2E in an individual. Other methods provided include a method for identifying a therapeutic compound for the treatment of ischemic heart disease in an individual caused by reduced expression of the sarcoglycan-sarcospan complex in the vascular smooth muscle cells of the individual, and also a method for identifying a therapeutic compound for the prevention of ischemic injury in skeletal and cardiac muscle of an individual which is caused by reduced expression of the sarcoglycansarcospan complex in vascular smooth muscle cells of the individual. Excerpt(s): The sarcoglycan complex is a group of single pass transmembrane proteins (.alpha.,.beta.,.delta.and.gamma.-sarcoglycan) which is tightly associated with sarcospan to form a subcomplex within the dystrophin-glycoprotein complex (DGC) in skeletal and cardiac muscle (Campbell et al., Nature 338: 259-362 (1989); Yoshida et al., J. Biochem. 108: 748-752 (1990); Crosbie et al., J. Cell Biol. 145: 153-165 (1999)). The DGC is further comprised of dystrophin, the dystroglycan complex and the syntrophins (Hoffman et al., Cell 51: 919-928 (1987); Froehner et al., Soc. Gen. Physiol. Ser. 52: 197-207 (1997); Durbeej et al., Curr. Opin. Cell. Biol. 10: 594-601 (1998)). The expression of the sarcoglycan-sarcospan complex is necessary to target dystroglycan to the sarcolemma (Duclos et al., J. Cell Biol. 142: 1461-1471 (1998); Duclos et al., Neuromusc. Disord. 8: 30-
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38 (1998); Holt et al., Mol. Cell 1: 841-848 (1998); Straub et al., Am. J. Path. 153: 1623-1630 (1998)) which in turn confers a link between the extracellular matrix and the F-actin cytoskeleton (Ervasti et al., J. Cell Biol. 122: 809-823 (1993)). Thus, the DGC is thought to protect muscle cells from contraction-induced damage (Petrof et al., Proc. Natl. Acad. Sci. USA 90: 3710-3714 (1993)). In agreement with this hypothesis, mutations in the genes for the sarcoglycans, dystrophin and laminin.alpha.2 chain are responsible for limb-girdle muscular dystrophy, Duchenne/Becker muscular dystrophy and congenital muscular dystrophy respectively (Straub et al., Curr. Opin. Neurol. 10: 168-175 (1997); Lim et al., Curr. Opin. Neurol. 11: 443-452 (1998)). Clinical evidence of cardiomyopathy is variably present in these muscular dystrophies (Towbin, J. A., Curr. Opin. Cell Biol. 10: 131-139 (1998)) but a correlation between the primary mutation of the sarcoglycan genes and cardiomyopathy is yet to be established (Melacini et al., Muscle & Nerve 22: 473-479 (1999)). Dilated cardiomyopathy is a multifactorial disease that includes both inherited and acquired forms of cardiomyopathy. Inherited cardiomyopathy in humans can be associated with genetic defects occurring in components of the dystrophinglycoprotein complex (DGC) (Towbin, J. A., Curr. Opin. Cell Biol. 10: 131-139 (1998)). Mutations in the dystrophin gene lead to a high incidence of cardiomyopathy in Duchenne and Becker muscular dystrophy patients (DMD/BMD) and can cause Xlinked dilated cardiomyopathy (Towbin, J. A., Curr. Opin. Cell Biol. 10: 131-139 (1998)). In addition to these primary genetic causes of cardiomyopathy, recent data suggest that disruption of the DGC underlie the cardiomyopathy associated with enteroviral infection (Badorff et al., Nat. Med. 5: 320-326 (1999)). Consequently, evidence is accumulating that the DGC plays a critical role in the pathogenesis of some forms of inherited and acquired cardiomyopathy. Several components of the DGC are also expressed in smooth muscle (Houzelstein et al., J. Cell Biol. 119: 811-821 (1992); North et al., J. Cell Biol. 120: 1159-1167 (1993); Ozawa, et al., Hum. Mol. Gen. 4: 1711-1716 (1995); Durbeej et al., Curr. Opin. Cell. Biol. 10: 594-601 (1998)). Interestingly, potential smooth muscle dysfunction has been described in patients with Duchenne muscular dystrophy (Bahron et al., N. Engl. J. Med. 319: 15-18 (1998); Jaffe et al., Arch. Phys. Med. Rehabil. 71: 742-744 (1990)). However, no smooth muscle dysfunction has been reported in patients with limb-girdle muscular dystrophy. Recently, a fifth sarcoglycan,.epsilon.sarcoglycan, was cloned and shown to be highly homologous to.alpha.-sarcoglycan (Ettinger et al., J. Biol. Chem. 272: 32534-32538 (1997); McNally et al., FEBS Lett. 422: 2732 (1998)).epsilon.-sarcoglycan is expressed in skeletal and cardiac muscle, but also in several non-muscle tissues. Whether.epsilon.-sarcoglycan is associated with the other sarcoglycans in striated muscle is yet to be determined. At the immunofluorescence level, however, it has been shown that.epsilon.-sarcoglycan is still present in skeletal muscle of.alpha.-sarcoglycan deficient (Sgca-null mice) mice although the other sarcoglycans are greatly reduced (Duclos et al., J. Cell Biol. 142: 1461-1471 (1998)). This indicates that.epsilon.-sarcoglycan is not an additional member of the known tetrameric complex of.alpha.-,.beta.-,.gamma.- and.delta.-sarcoglycan in skeletal muscle but may be part of a distinct complex at the sarcolemma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pd-1-lacking mouse and use thereof Inventor(s): Honjo, Tasuku; (Kyoto-shi, JP), Nishimura, Hiroyuki; (Boston, MA) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20040034881 Date filed: September 29, 2003 Abstract: It relates to BALB/c mice that defect programmed cell death-1 receptor (PD-1), a screening method of autoimmune disease medicine by use of these mice, IgG selfreactivity antibody that the mice produce specifically, protein specifically reacted to the antibody and produced in heart, and an diagnostic method in dilated cardiomyopathy by use of the protein.Because PD-1 deficient BALB/c mice spontaneously develop autoimmune disease, specifically dilated cardiomyopathy, they are useful to screening for medicines against these diseases. Excerpt(s): The present invention relates to programmed cell death-1 receptor (hereafter, it is abbreviated as PD-1)-deficient BALB/c mice and the use. More particularly, it relates to PD-1 receptor-deficient BALB/c mice, a screening method of medicines against autoimmune disease by use of the mice, IgG self-reactivity antibody of which these mice produce specifically, a protein specifically reacted to the antibody and produced in heart and an diagnostic method in dilated cardiomyopathy by use of the protein. Programmed cell death controlled embryologically or physiologically can be observed in all most tissues of various animals. Such programmed cell death is generally called, "Programmed cell death or Premeditated programmed cell death", and distinguished from unexpected cell death which could be caused by a pathologic mechanism. First, PD-1 has been found in mice as a receptor that cells are related to process to premeditated programmed cell death through the activation (The EMBO J., vol. 11(11), 3887-3895(1992); JP05-336973; EMBL/GenBank/DDJB Acc. No.X67914). Then, it has been found in human by using the gene of mouse PD-1 as a probe (Genomics 23:704 (1994); JP07-291996). Because PD-1 has expressed in lymphocytes with activation and has deeply related to autoimmune disease by researches of PD-1 deficient mice (International Immunology, Vol.10(10), 1563-1572(1998); Immunity. Vol.11, 141151(1999)), it has been suggested to be used for treatments and diagnoses of decrease or accentuation of immune function, infectious disease, rejections in transplant and tumours, etc. Both mouse and human PD-1 are composed by 288 amino acids, and are type I membrane-bound 55 kDa proteins with the hydrophobic region in the penetrative area of the cell-membrane in the middle and the signal peptide (20 amino-acids) in the N-terminus. Deficient mice (called the knockout mice.) are indicated those which cannot produce the gene product in born by modifying a specific gene artificially, and are made to examine roles of factors and receptors that are the gene products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preventing and/or treating cardiovascular disease and/or associated heart failure Inventor(s): Baker, John R.; (Auckland, NZ), Cooper, Garth J. S.; (Auckland, NZ) Correspondence: Buchanan Ingersoll, P.C.; One Oxford Centre, 301 Grant Street; 20th Floor; Pittsburgh; PA; 15219; US Patent Application Number: 20030203973 Date filed: March 12, 2003
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Abstract: Methods are provided for reducing copper values for, by way of example, treating, preventing or ameliorating tissue damage such as, for example, tissue damage that may be caused by (i) disorders of the heart muscle (for example, cardiomyopathy or myocarditis) such as idiopathic cardiomyopathy, metabolic cardiomyopathy which includes diabetic cardiomyopathy, alcoholic cardiomyopathy, drug-induced cardiomyopathy, ischemic cardiomyopathy, and hypertensive cardiomyopathy, (ii) atheromatous disorders of the major blood vessels (macrovascular disease) such as the aorta, the coronary arteries, the carotid arteries, the cerebrovascular arteries, the renal arteries, the iliac arteries, the femoral arteries, and the popliteal arteries, (iii) toxic, druginduced, and metabolic (including hypertensive and/or diabetic disorders of small blood vessels (microvascular disease) such as the retinal arterioles, the glomerular arterioles, the vasa nervorum, cardiac arterioles, and associated capillary beds of the eye, the kidney, the heart, and the central and peripheral nervous systems, (iv) plaque rupture of atheromatous lesions of major blood vessels such as the aorta, the coronary arteries, the carotid arteries, the cerebrovascular arteries, the renal arteries, the iliac arteries, the fermoral arteries and the popliteal arteries, (v) diabetes or the complications of diabetes. Excerpt(s): This application claims priority from U.S. Provisional Patent Application Serial No. 60/364,382, filed Mar. 12, 2002, New Zealand Provisional Patent Application Serial No. 517725, filed Mar. 12, 2002, and a corresponding PCT application filed on Mar. 10, 2003 (Serial No. NZ/03/00042), the contents of each of which are hereby incorporated in their entirety by reference. This invention concerns methods of treatment, prevention or amelioration of a disease, disorder or condition in a mammal (hereafter "treating"), including, for example, a human being, having undesired copper levels that cause or lead to tissue damage. Treating of mammals includes those, for example, predisposed to copper-involved or -mediated free radical damage of tissue and/or to copper-involved or -mediated impairment of normal tissue stem cell responses. The invention has application inter alia to diabetes-related and non-diabetesrelated heart failure, macrovascular disease or damage, microvascular disease or damage, and/or toxic (e.g., hypertensive) tissue and/or organ disease or damage (including such ailments as may, for example, be characterized by heart failure, cardiomyopathy, myocardial infarction, and related arterial and organ diseases) and to related compounds, compositions, formulations, uses, and procedures. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art, or relevant, to the presently described or claimed inventions, or that any publication or document that is specifically or implicitly referenced is prior art. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process and intermediates for pyridazinone antidiabetic agents Inventor(s): Tom, Norma J.; (Waterford, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030162969 Date filed: January 7, 2003 Abstract: The present invention relates to a process for preparing pyridazinone aldose reductase inhibitors which are useful in the prevention and/or treatment of diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy,
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diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. The invention also relates to novel intermediates useful in preparing those aldose reductase inihibitors. Excerpt(s): The present invention relates to a process for preparing sulfonyl pyridazinone aldose reductase inhibitors. The present invention also relates to novel intermediates used in the process to prepare those aldose reductase inhibitors. Accordingly, the comopunds prepared by the process of this invention lower sorbitol levels and, thus, lower fructose levels and have utility in the treatment and/or prevention of diabetic complications such as diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic microangiopathy and diabetic macroangiopathy in mammals. The enzyme aldose reductase is involved in regulating the reduction of aldoses, such as glucose and galactose, to their corresponding polyols, such as sorbitol and galactitol. Sulfonyl pyridazinone compounds of Formula I of this invention, prodrugs of such compounds and pharmaceutically acceptable salts of such compounds and prodrugs, are useful as aldose reductase inhibitors in the treatment and prevention of diabetic complications of humans and other mammals associated with increased polyol levels in certain tissues (e.g., nerve, kidney, lens and retina tissue) of affected humans and other mammals. wherein A, R.sup.1, R.sup.2 and R.sup.3 are defined as set forth therein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Processes and intermediates for preparing glycogen phosphorylase inhibitors Inventor(s): Barrila, Mark T.; (East Lyme, CT), Busch, Frank R.; (Gales Ferry, CT), Couturier, Michel A.; (Pawcatuck, CT), Orrill, Susan L.; (Gales Ferry, CT), Rose, Peter R.; (Ledyard, CT), Tickner, Derek L.; (Waterford, CT), Tobiassen, Harry O; (Ledyard, CT), Withbroe, Gregory J.; (Gales Ferry, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030187051 Date filed: January 16, 2003 Abstract: The instant invention provides novel processes and intermediates useful in the preparation of certain N-(indole-2-carbonyl)-.beta.-alaninamide compounds, which compounds are glycogen phosphorylase inhibitors useful in the treatment of diseases such as hypercholesterolemia, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis, diabetes, diabetic cardiomyopathy, infection, tissue ischemia, myocardial ischemia, and in inhibiting tumor growth. Excerpt(s): The instant invention provides novel processes and intermediates useful in the preparation of certain N-(indole-2-carbonyl)-.beta.-alanina- mide compounds, which compounds are glycogen phosphorylase inhibitors useful in the treatment of diseases such as hypercholesterolemia, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis, diabetes, diabetic cardiomyopathy, infection, tissue ischemia, myocardial ischemia, and in inhibiting tumor growth. Despite the early discovery of insulin and its subsequent widespread use in the treatment of diabetes, and the later discovery of, and use of, sulfonylureas (e.g. Chlorpropamide.TM. (Pfizer), Tolbutamide.TM. (Upjohn), Acetohexamide.TM. (E. I. Lilly), Tolazamide.TM. (Upjohn), and biguanides (e.g. Phenformin.TM. (Ciba Geigy), and Mefformin.TM. (G. D. Searle)) as oral hypoglycemic agents, therapeutic regimens for the treatment of diabetes remain
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less than satisfactory. The use of insulin, necessary in about 10% of diabetic patients in which synthetic hypoglycemic agents are not effective (Type 1 diabetes, insulin dependent diabetes mellitus), requires multiple daily doses, usually by self-injection. Determination of the proper dosage of insulin requires frequent estimations of sugar levels in the urine or blood. The administration of an excess dose of insulin causes hypoglycemia, with effects ranging from mild abnormalities in blood glucose to coma, or even death. Treatment of non-insulin dependent diabetes mellitus (Type 2 diabetes) usually consists of a combination of diet, exercise, oral agents, e.g., sulfonylureas, and, in more severe cases, insulin. However, clinically available hypoglycemic agents can have other side effects that limit their use. In any event, where one of these agents may fail in an individual case, another may succeed. A continuing need for hypoglycemic agents, which may have fewer side effects or succeed where others fail, is clearly evident. Atherosclerosis, a disease of the arteries, is recognized to be the leading cause of death in the United States and Western Europe. The pathological sequence leading to atherosclerotic development and occlusive heart disease is well known. The earliest stage in this sequence is the formation of "fatty streaks" in the carotid, coronary, and cerebral arteries, and in the aorta. These lesions are yellow in color due to the presence of lipid deposits found principally within smooth-muscle cells and in macrophages of the intima layer of the arteries and aorta. It is further postulated that most of the cholesterol found within the fatty streaks, in turn, gives rise to development of the socalled "fibrous plaque", which consists of accumulated intimal smooth muscle cells laden with lipid and surrounded by extra-cellular lipid, collagen, elastin, and proteoglycans. These cells, plus matrix, form a fibrous cap that covers a deeper deposit of cell debris and more extra cellular lipid, which comprises primarily free and esterified cholesterol. The fibrous plaque forms slowly, and is likely in time to become calcified and necrotic, advancing to the so-called "complicated lesion" which accounts for the arterial occlusion and tendency toward mural thrombosis and arterial muscle spasm that characterize advanced atherosclerosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Side-exit catheter and method for its use Inventor(s): Lederman, Robert J.; (Chevy Chase, MD) Correspondence: Klarquist Sparkman, Llp; One World Trade Center, Suite 1600; 121 S.W. Salmon Street; Portland; OR; 97204; US Patent Application Number: 20030032936 Date filed: August 10, 2001 Abstract: Disclosed is a device for delivering a therapeutic or diagnostic agent to an anatomic position, such as a heart. The device includes a flexible catheter having a proximal end and a distal end, a guide wire lumen that extends longitudinally through the catheter, and a delivery lumen that extends longitudinally at least partially through the catheter. The delivery lumen communicates with a side port adjacent a distal end of the catheter, through which side port a therapeutic or diagnostic agent may be delivered. The device also may include a guide wire, and the catheter may be advanced along the guide wire via the guide wire lumen. The device also may include a secondary catheter capable of sliding through the delivery lumen and capable of delivering a liquid, solid, or radiant agent to a desired anatomic location; thus, the secondary catheter may be considered a delivery catheter. The device may be used to deliver a therapeutic agent to a particular body location in a subject suffering a disease. In certain
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embodiments, the device may be used to deliver an ablative agent to the heart of a subject suffering hypertrophic cardiomyopathy. Excerpt(s): This invention relates to medical devices for delivering therapeutic and diagnostic agents to particular regions of the body, including catheters for delivering such agents into the heart, and methods for their use. Heart tissue (myocardium) may be altered by delivering drugs, electromagnetic energy, or mechanical force to the myocardium through the inner layer of the heart (the endocardium) via a process called "endomyocardial delivery." In some cases of heart disease, enlargement or excess growth of myocardium obstructs the flow of blood from the heart. For example, in the heart disease "hypertrophic cardiomyopathy," a region of heart tissue dividing the two ventricles located beneath the aortic valve is sometimes enlarged and obstructs blood flow from the left ventricle into the aorta. Treatments for such cases of heart disease often include the selective surgical removal of the excess heart tissue, a procedure called "septal myotomy-myectomy." However, a different therapeutic treatment has been proposed that includes selectively and intentionally damaging excess myocardium using a drug (such as ethanol or phenol), laser energy, or electromagnetic radiation (such as laser or radiofrequency energy) to locally reduce the heart wall thickness. Reducing the thickness of the myocardium consequently improves the flow of blood from the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Stromal cell-derived factor-1 mediates stem cell homing and tissue regeneration in ischemic cardiomyopathy Inventor(s): Askari, Arman T.; (University Heights, OH), Kiedrowski, Matthew; (Lorain, OH), Penn, Marc S.; (Shaker Heights, OH) Correspondence: Tarolli, Sundheim, Covell & Tummino L.L.P.; Suite 1111; 526 Superior Avenue; Cleveland; OH; 44114-1400; US Patent Application Number: 20040037811 Date filed: April 30, 2003 Abstract: A method of treating infarcted myocardial tissue includes, the concentration of SDF-1 protein in the infarcted tissue. The concentration of stem cells in the peripheral blood of the infarcted tissue is also increased. The number of stem cells in the peripheral blood is increased while the concentration of SDF-1 in the infarcted tissue is increased. Excerpt(s): The present invention relates to a method of tissue regeneration in ischemic cardiomyopathy and particularly relates to a method of treating ischemic cardiomyopathy at a time remote (i.e., weeks) from myocardial infarction. Acute myocardial infarction (MI) remains the leading cause of morbidity and mortality in western society. Despite recent therapeutic advances predominantly targeted at restoring antegrade perfusion in the infarct-related artery, a "ceiling" of benefit appears to exist. Topol, E. J. Lancet 357, 1905-1914 (2001). A substantial proportion of patients who experience an acute myocardial infarction (MI) ultimately develop congestive heart failure (CHF) largely as a result of left ventricular (LV) remodeling, a process involving myocardial thinning, dilation, decreased function, ultimately leading to death. Robbins, M. A. & O'Connell, J. B., pp. 3-13 (Lippincott-Raven, Philadelphia, 1998). Pfeffer, J. M., Pfeffer, M. A., Fletcher, P. J. & Braunwald, E. Am. J. Physiol 260, H1406-H1414 (1991). Pfeffer, M. A. & Braunwald, E. Circulation 81, 1161-1172 (1990). One method to treat this process following myocardial infarction involves cell therapy. Penn, M. S. et al. Prog.
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Cardiovasc. Dis. 45, 21-32 (2002). Transplantation has focused on using a variety of cell types including differentiated cells, such as skeletal myoblasts, cardiac myocytes, smooth muscle cells, and fibroblasts, or bone marrow derived cells. Koh, G. Y., Klug, M. G., Soonpaa, M. H. & Field, L. J. J. Clin. Invest 92, 1548-1554 (1993). Taylor, D. A. et al. Nat. Med. 4, 929-933 (1998). Jain, M. et al. Circulation 103, 1920-1927 (2001). Li, R. K. et al. Ann. Thorac. Surg. 62, 654-660 (1996). Etzion, S. et al. J. Mol. Cell Cardiol. 33, 13211330 (2001). Li, R. K., Jia, Z. Q., Weisel, R. D., Merante, F. & Mickle, D. A. J. Mol. Cell Cardiol. 31, 513-522 (1999). Yoo, K. J. et al. Yonsei Med. J. 43, 296-303 (2002). Sakai, T. et al. Ann. Thorac. Surg. 68, 2074-2080 (1999). Sakai, T. et al. J. Thorac. Cardiovasc. Surg. 118, 715-724 (1999). Orlic, D. et al. Nature 410, 701-705 (2001). Tomita, S. et al. J. Thorac. Cardiovasc. Surg. 123, 1132-1140 (2002). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
System for the diagnosis and monitoring of coronary artery disease, acute coronary syndromes, cardiomyopathy and other cardiac conditions Inventor(s): Arenare, Brian; (Houston, TX), Schlegel, Todd T.; (Nassau Bay, TX) Correspondence: Nasa Johnson Space Center; Mail Code HA; 2101 Nasa RD 1; Houston; TX; 77058; US Patent Application Number: 20040039292 Date filed: March 26, 2003 Abstract: Cardiac electrical data are received from a patient, manipulated to determine various useful aspects of the ECG signal, and displayed and stored in a useful form using a computer. The computer monitor displays various useful information, and in particular graphically displays various permutations of reduced amplitude zones and kurtosis that increase the rapidity and accuracy of cardiac diagnoses. New criteria for reduced amplitude zones are defined that enhance the sensitivity and specificity for detecting cardiac abnormalities. Excerpt(s): The invention described herein was made in the performance of work under a NASA contract and is subject to the provisions of Section 305 of the National Aeronautics and Space Act of 1958, Public Law 85-568 (72 Stat. 435; 42 U.S.C. 2457). The present invention relates generally to the field of electrocardiography, and more particularly to a non-invasive, real-time processing system and method to analyze, process, store, recall and display electrocardiographic signals. Cardiovascular disease remains the leading cause of death in North America, with more than 1.6 million myocardial infarctions (MIs) occurring annually in the United States alone. Although substantial advancement in the care of patients with ischemic heart disease has recently contributed to a 20-25% improvement in survival rate, primary preventive interventions with a similar impact on survival could, in theory, avert more than five times as many cardiovascular deaths each year. Clinicians providing preventive care for apparently healthy individuals therefore have an important opportunity to reduce the adverse impact of cardiovascular disease in the community to the extent that they can identify patients at high risk for future vascular events. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Transluminal mitral annuloplasty Inventor(s): Burg, Erik van der; (Sunnyvale, CA), Langberg, Jonathan J.; (Atlanta, GA), Lesh, Michael D.; (Mill Valley, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020103532 Date filed: July 19, 2001 Abstract: A mitral annuloplasty and left ventricle restriction device is designed to be transvenously advanced and deployed within the coronary sinus and in some embodiments other coronary veins. The device places tension on adjacent structures, reducing the diameter and/or limiting expansion of the mitral annulus and/or limiting diastolic expansion of the left ventricle. These effects may be beneficial for patients with dilated cardiomyopathy. Excerpt(s): This application is a divisional of U.S. application Ser. No. 09/774,869 filed on Jan. 30, 2001, entitled Percutaneous Mitral Annuloplasty and Deployment Device. The present invention relates to intravascular prostheses for remodeling an extravascular anatomical structure. In one application, the present invention relates to a mitral annuloplasty and cardiac reinforcement device which is transluminally implantable in the coronary sinus. Dilated cardiomyopathy occurs as a consequence of many different disease processes that impair myocardial function, such as coronary artery disease and hypertension. The left ventricle enlarges and the ejection fraction is reduced. The resulting increase in pulmonary venous pressure and reduction in cardiac output cause congestive heart failure. Enlargement of the mitral annulus and left ventricular cavity produce mitral valvular insufficiency. This in turn, causes volume overload that exacerbates the myopathy, leading to a vicious cycle of progressive enlargement and worsening mitral regurgitation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of cardiomyopathy by removal of autoantibodies Inventor(s): Baumann, Gert; (Berlin, DE), Brehme, Stefan; (Berlin, DE), Felix, Stephan; (Falkensee, DE), Koll, Robert; (Kirchheim, DE), Muller-Derlich, Jutta; (Germering, DE), Reinke, Petra; (Berlin, DE), Spaethe, Reiner; (Stamberg, DE) Correspondence: Edwards Lifesciences Llc; Law DEPT.; One Edwards Way; Irvine; CA; 92614; US Patent Application Number: 20030125657 Date filed: November 19, 2002 Abstract: Immunoapheresis treatment for cardiomyopathy comprises passing the patient's plasma over a column having coupled thereto a specific ligand for human immunoglobulin, thereby removing a significant portion of the immunoglobulin from the patient's plasma, and then reinfusing the plasma to the patient. The invention is the use of a specific ligand for human immunoglobulin in the manufacture of a column having the ligand coupled thereto, the column being useful for immunoapheresis treatment of a patient with cardiomyopathy. The specific ligand binds, and thereby removes, human autoantibodies which are harmful to cardiac tissue such as antibodies against.beta.sub.1-adrenergic receptors, ADP-ATP carriers,.alpha. and.beta. myosin
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heavy chains, and adenine nucleotide translocators. Immunoapheresis treatment using the column results in improvement of hemodynamic parameters such as mean arterial pressure, mean pulmonary pressure, pumonary capillary wedge pressure, right atrial pressure, cardiac output, cariac index, stroke volume index, and systemic vascular resistance. Excerpt(s): Acute and chronic myocarditis is often accompanied by the prevalence of high affinity anti-beta-1 receptor autoantibodies in high titers. Like the catecholamines, these anti-beta-1 receptor autoantibodies activate the beta-adrenergic system. Possible clinical consequences include the destruction of cardial structures with subsequent cardiac insufficiency in the context of a dilatative cardiomyopathy, and persisting arrhythmias as a consequence of the sympathomimetic effect of the anti-beta-1 receptor autoantibodies. These anti-beta-1 receptor autoantibodies correlate with the severity of dilatative cardiomyopathy. In a clinical trial, the removal of antibodies with the IgTherasorb system as described below correlated with the clinical improvement in the patients treated. The clinical results are shown below. Treatment with the Ig-Therasorb system effects the removal of a high proportion of antibodies of all classes and IgGsubclasses and therefore of antibodies directed against cardiac structures, namely antibeta-1 receptor autoantibodies. This treatment also removes antibodies of any other specificity against cardiac tissue. It is postulated that removal of these autoantibodies is the basis for the efficacy of Ig-Therasorb treatment of patients with cardiomyopathy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of diabetes and diabetic complications with NHE-1 inhibitors Inventor(s): Tracey, W. Ross; (Niantic, CT), Treadway, Judith L.; (Mystic, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030212104 Date filed: May 1, 2003 Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/380,028 filed May 2, 2002. This invention relates to methods of treating or preventing type 2 diabetes, diabetic neuropathy, diabetic cardiomyopathy, cataracts, diabetic retinopathy, foot ulcers, diabetic microangiopathy, diabetic macroangiopathy, diabetic ischemia reperfusion injury, diabetic cardiac ischemia reperfusion injury and/or insulin resistance syndrome (IRS) in mammals, particularly in humans, by administering a sodium-hydrogen exchanger type 1 (NHE-1) inhibitor or a pharmaceutical composition containing such an inhibitor. This invention also relates to combinations comprising NHE-1 inhibitors and a second pharmaceutical agent, said combinations being useful in treating type 2 diabetes, IRS, diabetic neuropathy, diabetic cardiomyopathy, cataracts, diabetic retinopathy, foot ulcers, diabetic ischemia reperfusion injury, diabetic cardiac ischemia reperfusion injury, diabetic microangiopathy and/or diabetic macroangiopathy. (1) Type 1 diabetes, or insulin-dependent diabetes mellitus (IDDM), which arises when patients lack insulin-producing.beta.-cells in their pancreatic glands, and (2) Type 2 diabetes, or non-insulin dependent diabetes mellitus (NIDDM), which occurs in patients with, inter alia, impaired.beta.-cell function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of hibernating myocardium and diabetic cardiomyopathy with a GLP-1 peptide Inventor(s): Coolidge, Thomas R.; (Falls Village, CT), Ehlers, Mario; (Lincoln, NE) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20020146405 Date filed: October 22, 2001 Abstract: Hibernating myocardium is characterized by viable myocardium with impaired function due to localized reduced perfusion. Hibernating myocytes retain cellular integrity, but cannot sustain high-energy requirements of contraction. High plasma levels of catecholamines, such as norepinepherine, are believed to be predictive of mortality from hibernating myocardium. Likewise, high levels of catecholamines lead to cardiomyopathy in patients with diabetes. GLP-1 reduces plasma norepinepherine levels, and it thus is useful in a method of treating hibernating myocardium or diabetic cardiomyopathy. Excerpt(s): This application claims priority to U.S. Application Ser. Nos. 60/241,834, filed Oct. 20, 2000, 60/60/242,139, filed Oct. 23, 2000, and 60/245,234, filed Nov. 3, 2000, all of which are hereby incorporated by reference. Heart failure continues to be a major health problem. Approximately four million persons in the U.S. population have heart failure. With a steadily aging population, four hundred thousand individuals experience new onset heart failure each year, with a five year mortality rate approaching fifty percent. Rather than a single pathological entity, "heart failure" defines a clinical syndrome with many different etiologies that reflects a fundamental abnormality in effective mechanical performance of the heart, such that the heart is unable to meet the demands of the body. There are various forms of heart failure, including "forward" and "backward" heart failure. Backward failure, synonymous with congestive heart failure, is due to increase in venous pressure (i.e., increase in pressure in the veins that return blood to the heart) resulting from the inability of the heart to discharge its contents normally, leading to pulmonary and systemic congestion. By contrast, forward failure is caused by an inability of the heart to maintain normal tissue perfusion, resulting in fatigue, weakness, loss of weight, and impairment of cerebral function. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Use of somatostatin receptor agonists in the treatment of human disorders of sleep hypoxia and oxygen deprivation Inventor(s): Young, Charles W.; (New York, NY) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20030083241 Date filed: October 25, 2002 Abstract: The invention relates to a method of treating diverse human disorders that may arise, in part, out of sleep hypoxia and oxygen deprivation occurring in the context of sleep apnea/hypopnea disturbances. The disorders that may be treated by the invention comprise gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, asthma, cardiomyopathy,
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cardioarrhythmia, congestive heart failure, sudden infant death syndrome, and diverse neurologic conditions. The mode of treatment uses somatostatin receptor ligands (SstRLs), particularly somatostatin-receptor agonists. The invention concerns the method of treatment utilizing, and compositions comprising SstRLs and somatostatin receptor agonists, including agonists of the somatostatin receptor types 2 and 5, particularly, the type 2A receptor (SsR-2A), including octreotide and lanreotide. Excerpt(s): The invention relates to a method of using somatostatin receptor agonists to treat diverse human disorders of sleep hypoxia and oxygen deprivation, including but not limited to: 1) gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, and asthma; 2) obstructive sleep apnea (OSA), and OSA-associated conditions, including GER, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, median nerve compression neuropathy (carpal tunnel syndrome) and cognitive impairment; as well as sleep apnea-associated sudden infant death syndrome (SIDS), 3) central sleep apnea (CSA), as well as CSAassociated conditions, including GER, cardiomyopathy, cardioarrhythmia, congestive heart failure, and cognitive impairment; 4) mixed pattern sleep apneas, including but not limited to post-vascular occlusion sleep apnea, dementia-associated sleep apnea, amyotrophic lateral sclerosis-associated sleep apnea, myasthenia gravis-associated sleep apnea, and alcoholism-related sleep apnea; 5) excess calpain-activation disorders in tissues where the injured cell population expresses somatostatin receptors; including, but not limited to the central nervous system, peripheral nerves, heart, liver, kidney, and gastrointestinal tract. Various documents are cited in this text. Citations in the text can be by way of a citation to a document in the reference list, e.g., by way of an author(s) and document year, whereby full citation in the text is to a document that may or may not also be listed in the reference list. There is no admission that any of the various documents cited in this text are prior art as to the present invention. Any document having as an author or inventor person or persons named as an inventor herein is a document that is not by another as to the inventor of entity herein. All documents cited in this text ("herein cited documents") and all documents cited or referenced in herein cited documents are hereby incorporated herein by reference. 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 cardiomyopathy, 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 “cardiomyopathy” (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 cardiomyopathy. You can also use this procedure to view pending patent applications concerning cardiomyopathy. 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 7. BOOKS ON CARDIOMYOPATHY Overview This chapter provides bibliographic book references relating to cardiomyopathy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on cardiomyopathy include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “cardiomyopathy” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on cardiomyopathy: •
Cardiac Dysfunction in Chronic Uremia Source: Norwell, MA: Kluwer Academic Publishers. 1992. 231 p. Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $145 plus shipping and handling. Summary: Cardiac disease is the major cause of death in dialysis patients, accounting for over one-third of deaths. This book focuses on myocardial function and dysfunction in chronic uremia. It is written for practicing and training nephrologists, cardiologists, and internists, and for research workers in the field. The first section comprises five chapters that provide an overview of the burden of illness associated with cardiac disease in endstage renal disease and a review of clinical epidemiological aspects of various cardiac diseases that occur in renal patients. The second section discusses abnormalities of left ventricular contractility and mass, and the factors that predispose to both systolic and
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diastolic disorders. The importance of hypertension, anemia, hyperparathyroidism, hyperlipidemia, and diabetes mellitus is reviewed. The final section concentrates on therapeutics. Data and opinion on management of congestive heart failure, cardiomyopathy, coronary artery disease, hypertension, and arrhythmias are provided. Each chapter includes numerous references and a subject index is appended to the volume. (AA-M).
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 “cardiomyopathy” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “cardiomyopathy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “cardiomyopathy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Advances in Cardiomyopathies by F. Camerini, et al; ISBN: 0387510680; http://www.amazon.com/exec/obidos/ASIN/0387510680/icongroupinterna
•
Arrhythmogenic Right Ventricular Cardiomyopathy (Clinical Approaches to Tachyarrhythmias, V. 17) by Paul Touboul, et al; ISBN: 0879937122; http://www.amazon.com/exec/obidos/ASIN/0879937122/icongroupinterna
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Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia by Andrea Nava (Editor), et al; ISBN: 0444824472; http://www.amazon.com/exec/obidos/ASIN/0444824472/icongroupinterna
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Atlas of Heart Diseases: Cardiomyopathies, Myocarditis, and Pericardial Disease (Vol. II) by Walter H. Abelmann (Editor), et al; ISBN: 1878132245; http://www.amazon.com/exec/obidos/ASIN/1878132245/icongroupinterna
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Cardiac Failure: Cardiomyopathies and Inflammatory Disorders by Walter H., M.D. Abelmann, Barry M. Massic; ISBN: 1859226027; http://www.amazon.com/exec/obidos/ASIN/1859226027/icongroupinterna
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Cardiac Positron Emission Tomography: Viability, Perfusion, Receptors and Cardiomyopathy (Developments in Cardiovascular Medicine, 166) by E.E. Van Der Wall, et al; ISBN: 0792334728; http://www.amazon.com/exec/obidos/ASIN/0792334728/icongroupinterna
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Cardiomyopathies; ISBN: 0839107005; http://www.amazon.com/exec/obidos/ASIN/0839107005/icongroupinterna
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Cardiomyopathies and Heart Failure: Biomolecular, Infectious, and Immune Mechanisms (Developments in Cardiovascular Medicine, 248) by Akira, Md. Matsumori (Editor); ISBN: 1402074387; http://www.amazon.com/exec/obidos/ASIN/1402074387/icongroupinterna
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Cardiomyopathies and Heart-Lung Transplantation by Amar S. Kapoor (Editor), Hillel Laks; ISBN: 0070335702; http://www.amazon.com/exec/obidos/ASIN/0070335702/icongroupinterna
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Cardiomyopathies: Clinical Presentation, Differential Diagnosis and Management (Cardiovascular Clinics, Vol 19, No 1) by James Shaver (Editor); ISBN: 0803678215; http://www.amazon.com/exec/obidos/ASIN/0803678215/icongroupinterna
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Cardiomyopathies: Realisations and Expectations by E.G.J. Olsen (Editor), John F. Goodwin; ISBN: 0387556087; http://www.amazon.com/exec/obidos/ASIN/0387556087/icongroupinterna
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Cardiomyopathy by Thomas D. Giles, Gary E. Sander (Editor); ISBN: 0884164640; http://www.amazon.com/exec/obidos/ASIN/0884164640/icongroupinterna
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Cardiomyopathy; ISBN: 0803614209; http://www.amazon.com/exec/obidos/ASIN/0803614209/icongroupinterna
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Cardiomyopathy associated with systemic myopathy : genetic defect of actomyosin influencing muscular structure and function by Franz Büchner; ISBN: 0806702419; http://www.amazon.com/exec/obidos/ASIN/0806702419/icongroupinterna
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Cardiomyopathy Update: Restrictive Cardiomyopathy and Arrhythmias, No. 3 by Mori Sekiguchi, et al; ISBN: 0860084582; http://www.amazon.com/exec/obidos/ASIN/0860084582/icongroupinterna
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Cytokines and the Heart:: Molecular Mechanisms of Septic Cardiomyopathy by Ursula Muller-Werdan; ISBN: 3540601759; http://www.amazon.com/exec/obidos/ASIN/3540601759/icongroupinterna
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Diagnosis and Management of Hypertrophic Cardiomyopathy by Barry J. Maron (Editor), Maron Barry; ISBN: 140511732X; http://www.amazon.com/exec/obidos/ASIN/140511732X/icongroupinterna
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Dilated Cardiomyopathy by Donald V Unverferth (Editor); ISBN: 0879932546; http://www.amazon.com/exec/obidos/ASIN/0879932546/icongroupinterna
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Drug Therapy in Dilated Cardiomyopathy and Myocarditis by Richard S. Engelmeier, John B. O'Connell (Editor); ISBN: 082477843X; http://www.amazon.com/exec/obidos/ASIN/082477843X/icongroupinterna
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Hypertrophic Cardiomyopathy; ISBN: 4130681303; http://www.amazon.com/exec/obidos/ASIN/4130681303/icongroupinterna
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Hypertrophic Cardiomyopathy by Kaltenbach; ISBN: 0387110658; http://www.amazon.com/exec/obidos/ASIN/0387110658/icongroupinterna
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Hypertrophic Cardiomyopathy (Cardiomyopathy Update, No 2) by Hironori Toshima (Editor), et al; ISBN: 0860084361; http://www.amazon.com/exec/obidos/ASIN/0860084361/icongroupinterna
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Hypertrophic Cardiomyopathy: Clinical Recognition and Management by Folkert J. Ten Cate (Editor); ISBN: 0824773748; http://www.amazon.com/exec/obidos/ASIN/0824773748/icongroupinterna
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Hypertrophic obstructive cardiomyopathy; Ciba Foundation Study Group no. 37; ISBN: 0700015094; http://www.amazon.com/exec/obidos/ASIN/0700015094/icongroupinterna
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Idiopathic Dilated Cardiomyopathy by H. -R Figulla; ISBN: 3540561323; http://www.amazon.com/exec/obidos/ASIN/3540561323/icongroupinterna
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Idiopathic Dilated Cardiomyopathy: Cellular and Molecular Mechanisms, Clinical Consequences by R. Kandolf, et al; ISBN: 0387561323; http://www.amazon.com/exec/obidos/ASIN/0387561323/icongroupinterna
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Metabolic and Molecular Aspects of Cardiomyopathy; ISBN: 4130681559; http://www.amazon.com/exec/obidos/ASIN/4130681559/icongroupinterna
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Metabolic and Molecular Aspects of Cardiomyopathy (Cardiomyopathy Update, 4) by Lionel H. Opie, Tsuneaki Sugimoto (Editor); ISBN: 0860084795; http://www.amazon.com/exec/obidos/ASIN/0860084795/icongroupinterna
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Molecular Mechanisms of Septic Cardiomyopathy (Medical Intelligence Unit) by Karl Werdan, Ursula Muller; ISBN: 1570591253; http://www.amazon.com/exec/obidos/ASIN/1570591253/icongroupinterna
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Myocardial Function in Man: Ischemia, Failure, Cardiomyopathies (Hammersmith Cardiology Workshop Series, Vol. 2) by Attilio Maseri (Editor); ISBN: 0881670383; http://www.amazon.com/exec/obidos/ASIN/0881670383/icongroupinterna
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Myocarditis: Cardiomyopathy: Selected Problems of Pathogenesis and Clinic by H. Just, H.P. Schuster (Editor); ISBN: 0387116176; http://www.amazon.com/exec/obidos/ASIN/0387116176/icongroupinterna
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Myocarditis: Precursor of Cardiomyopathy by John A. and O'Connell, John B. Robinson (Editor); ISBN: 0024025305; http://www.amazon.com/exec/obidos/ASIN/0024025305/icongroupinterna
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New Aspects of Hypertrophic Cardiomyopathy by M. Kaltenbach (Editor), et al; ISBN: 3798507473; http://www.amazon.com/exec/obidos/ASIN/3798507473/icongroupinterna
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Pathogenesis of Myocarditis and Cardiomyopathy: Recent Experimental and Clinical Studies (Cardiomyopathy Update 1) by Chuichi Kawai (Editor), Walter H., M.D. Abelmann (Editor); ISBN: 0860084191; http://www.amazon.com/exec/obidos/ASIN/0860084191/icongroupinterna
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Pathology of the cardiomyopathies by Brian McKinney; ISBN: 0407620001; http://www.amazon.com/exec/obidos/ASIN/0407620001/icongroupinterna
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Prognosis and treatment of cardiomyopathies and myocarditis; ISBN: 4130681567; http://www.amazon.com/exec/obidos/ASIN/4130681567/icongroupinterna
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Prognosis and Treatment of Cardiomyopathies and Myocarditis (Cardiomyopathy Update, 5) by Morie Sekiguchi (Editor), Peter J. Richardson (Editor); ISBN: 0860085112; http://www.amazon.com/exec/obidos/ASIN/0860085112/icongroupinterna
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Recent Views on Hypertrophic Cardiomyopathy (Developments in Cardiovascular Medicine, 44) by E. Van Der Wall, K.I. Lie (Editor); ISBN: 0898386942; http://www.amazon.com/exec/obidos/ASIN/0898386942/icongroupinterna
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Restrictive cardiomyopathy and arrhythmias; ISBN: 4130681540; http://www.amazon.com/exec/obidos/ASIN/4130681540/icongroupinterna
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The Official Patient's Sourcebook on Restrictive Cardiomyopathy by Icon Health Publications, et al; ISBN: 0597831556; http://www.amazon.com/exec/obidos/ASIN/0597831556/icongroupinterna
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The Pathogenesis of Myocarditis and Cardiomyopathy by Churchi Kawai (Editor), Walter H. Abelman (Editor); ISBN: 413068129X; http://www.amazon.com/exec/obidos/ASIN/413068129X/icongroupinterna
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Chapters on Cardiomyopathy In order to find chapters that specifically relate to cardiomyopathy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and cardiomyopathy 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 “cardiomyopathy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on cardiomyopathy: •
Cardiac Disease in Hemodialysis and Peritoneal Dialysis Patients Source: in Lameire, N. and Mehta, R.L., eds. Complications of Dialysis. New York, NY: Marcel Dekker, Inc. 2000. p. 269-302. Contact: Available from Marcel Dekker, Inc. Cimarron Road, P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (845) 796-1919. Fax (845) 796-1772. E-mail:
[email protected]. International E-mail:
[email protected]. Website: www.dekker.com. PRICE: $250.00 plus shipping and handling. ISBN: 0824788710. Summary: Cardiac disease exerts a major influence on the morbidity and mortality of dialysis patients, as demonstrated by the frequent occurrence of heart failure and ischemic heart disease, very high mortality (death) rates, and the high proportion of cardiac deaths. This chapter on cardiac disease in hemodialysis and peritoneal dialysis patients is from a book that offers a comprehensive, multidisciplinary resource for the nephrologist and caregiver providing dialysis, covering all aspects of dialysis therapies and their complications. Most reports point to similar survival in chronic ambulatory peritoneal dialysis (CAPD) and in center hemodialysis (HD) patients. On average, hospital admission rates per patient year were 14 percent higher for peritoneal dialysis (PD) patients than for HD patients after adjustment for race, age, gender, and cause of end stage renal disease (ESRD). However, the causes of this higher hospital admission rate in PD patients were not studied. The authors discuss myocardial disease, disorders of perfusion, cardiac structure and function, cardiac arrhythmias, and risk factors for cardiac disease. Hemodynamic risk factors discussed include volume overload, salt and water retention, anemia, hypertension, and aortic stenosis; metabolic risk factors discussed include hypoalbuminemia, abnormal calcium phosphate homestasis, dyslipidemia, hyperhomocysteinemia, and oxidant stress. The authors consider other risk factors, notably smoking, diabetes mellitus, and valvular calcifications in PD patients. The authors offer guidelines for screening patients for cardiovascular disease, including the clinical assessment of cardiac status, noninvasive testing for cardiomyopathy, noninvasive testing for coronary artery disease, coronary angiography, and screening for cardiac arrhythmias. The chapter concludes with guidelines for patient management in the areas of volume overload, anemia, hypertension, hyperlipidemia, hyperhomocysteinemia, management of heart failure, coronary artery revascularization, cardiac arrhythmias, and pericarditis. 12 figures. 7 tables. 287 references.
•
Cardiac Disease in Dialysis Patients Source: in Nissenson, A.R., Fine, R.N., and Gentile, D.E. Clinical Dialysis. 3rd ed. Norwalk, CT: Appleton and Lange. 1995. p. 652-698.
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Contact: Available from Appleton and Lange. 25 Van Zant Street, East Norwalk, CT 06855. PRICE: $215.00. ISBN: 0838513794. Summary: Heart disease is the leading cause of death in the dialysis population, accounting for nearly 40 percent of deaths among these patients. In this chapter, from a medical text on clinical dialysis, the authors examine disorders of the heart that are most prevalent in patients with chronic kidney failure. The authors also put into perspective the factors associated with end-stage renal disease (ESRD) and its treatment that adversely affect myocardial performance. They also discuss methods of evaluating these diseases in the dialysis population, and assess methods that may be useful in the management of heart disease in such individuals. Specific disorders include extracellular fluid and plasma volume overload, anemia, arteriovenous fistulas (for circulatory access), uremic cardiomyopathy, acquired valvular disease, and infective endocarditis. The results of dialysis on cardiac function include acute hemodynamic effects, effects in patients with normal and abnormal left ventricular function, recurrent hypotension, and disturbances of heart rhythm. The chapter concludes with a section discussing uremic pericarditis, a less frequent but more dramatic cardiac complication of uremia. 3 figures. 1 table. 570 references. •
Heart Failure in Diabetic Patients Source: in Johnstone, M.T. and Veves, A. Diabetes and Cardiovascular Disease. Totowa, NJ: The Humana Press, Inc. 2001. p. 281-297. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $125.00, plus shipping and handling. ISBN: 089603755X. Summary: Heart failure is a well-recognized clinical problem in patients with diabetes. The extent to which heart failure results from coexistent coronary artery disease (CAD) and systemic hypertension, versus primary cardiac dysfunction related to diabetes, remains hotly debated. This chapter on heart failure in people with diabetes is from a textbook that offers physicians practical knowledge about cardiovascular disease and diabetes. The authors discuss epidemiology of clinical heart failure, hypertension (high blood pressure) and diabetes, CAD and diabetes, diabetic cardiomyopathy (damage to the structure of the heart muscle), abnormalities in left ventricular function in patients with diabetes, the relationship between contractile abnormalities and diabetes complications, prognosis and response to heart failure therapy in patients with diabetes, cellular and molecular abnormalities in the diabetic heart, and metabolic abnormalities in the diabetic heart. The authors conclude that the epidemiological data strongly indicate that diabetes increases the incidence of heart failure, particularly in the presence of CAD and hypertension. Cellular and molecular abnormalities in the calcium handling, myofibrillar protein, and energy generating metabolic pathways are present in animal models of diabetes. Additional autonomic neuropathy (nerve damage) and microvasculature dysfunction may also compromise the diabetic heart. 2 figures. 160 references.
•
Diabetes Mellitus Source: in Wilson, J.D., et al., eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, PA: W.B. Saunders Company. 1998. p. 973-1059. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department. 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522 or (314) 453-
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7010. Fax (800) 568-5136 or (314) 453-7095. E-mail:
[email protected]. Website: www.wbsaunders.com. PRICE: $150.00 plus shipping and handling. ISBN: 0721661521. Summary: This chapter provides an overview of diabetes mellitus. This condition comprises a heterogenous group of hyperglycemic disorders. The chapter begins with a description of the tests used to diagnose diabetes, including measurement of fasting plasma glucose, glycosylated hemoglobin, and the muscle capillary basement membrane; the oral glucose tolerance test; and the intravenous glucose tolerance test. This is followed by a discussion of nomenclature and definitions. The chapter then provides detailed information on type 1 and type 2 diabetes. Topics related to both types of diabetes include their prevalence, incidence, genetics, and clinical features. Other topics relevant to type 1 diabetes include environmental-genetic interactions, islet antibodies, and superantigens. In addition, the natural history, prevention, and hormonal pathophysiology of type 1 diabetes are discussed. Topics related to the prevention of type 1 diabetes include potential prophylactic agents, immunomodulation in autoimmune diabetes, and the pathology of the Islets of Langerhans in type 1 diabetes. Topics concerning type 2 diabetes include islet cell function, hormonal pathophysiology, and molecular genetics. Molecular genetic topics include mutations in genes involved in insulin resistance, mutations in genes encoding beta cell proteins involved in the quality and quantity of secreted insulin, mutations in genes involved in lipid metabolism and obesity, mutations in genes relevant to insulin action, miscellaneous mutations in genes without known diabetogenicity, the current state of candidate genes, the inheritance of type 2 diabetes, and autoimmune type 2 diabetes. The chapter continues with a discussion of insulin resistance, management of the diabetic pregnancy, gestational diabetes, and surgery in diabetic patients. Information is provided on the complications of diabetes, including the role of metabolic control in preventing complications and the potential mechanisms in the pathogenesis of complications. Complications discussed include cardiomyopathy, dermopathy, diabetic foot syndrome, nephropathy, retinopathy, cataracts, neuropathy, and peripheral vascular disease. The issue of treatment is also addressed. Topics include the treatment of type 1 diabetes with insulin, diet, and exercise; the treatment of type 2 diabetes with diet, oral antihyperglycemic drugs, and insulin; the treatment of diabetic ketoacidosis and nonketotic hyperosmolar coma; the prevention and treatment of vascular complications; and pancreas and islet transplantation. 49 figures. 28 tables. 1207 references. •
Chapter 30: Amyloidoses Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 467-472. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This chapter provides health professionals with information on the pathology, pathogenesis, clinical features, and diagnosis of the amyloidoses. These represent the extracellular subset of a larger disease group related to tissue dysfunction resulting from aberrant protein conformation. Various pathogenic modes are involved. Increased production of a precursor as a result of prolonged normal stimulus to the synthesizing cell or monoclonal proliferation of a cell producing the amyloidogenic protein may be responsible. There may also be decreased excretion of the precursor. Aberrant, inappropriate, or incomplete proteolytic cleavage may lead to increased amounts of profibrillogenic precursor. Structural abnormalities of a normal protein may
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predispose to fibril formation. Amyloidosis is diagnosed by finding the characteristic staining in biopsies from clinically affected organs. Several nonfibril molecules are also found in amyloid deposits, including P-component, apolipoprotein E, and heparan sulfate proteoglycan perlecan. One form of amyloid deposition associated with athropathy is amyloid L (AL) disease. The usual presentation of AL is nephropathy with proteinuria or renal failure. The second most common presentation is cardiomyopathy. Some people who have AL disease have a dominant neuropathic presentation. In addition, periarticular amyloid deposition, presenting as pseudoarthritis, has been reported. Organ failure caused by extensive amyloid deposition is treated by supportive measures. Data suggest that all patients with AL should be offered treatment with melphalan and prednisone. The second form of amyloid deposition associated with a significant articular presentation is the deposition of beta 2 microglobulin (AB2m) related fibrils in patients who have chronic renal disease. The third rheumatologically associated form of amyloidosis is amyloid A (AA) disease. AA is found in people with chronic infectious diseases such as tuberculosis and osteomyelitis and noninfectious inflammatory diseases such as rheumatoid arthritis and familial Mediterranean fever. Evidence suggests a genetic predisposition toward AA deposition. The chapter also discusses the relationship between aging and amyloid deposition and the occurrence of familial amyloidosis. 2 tables and 25 references. •
Preventing Long-Term Complications Source: in Rubin, A.L. Diabetes for Dummies. Foster City, CA: IDG Books Worldwide, Inc. 1999. p. 57-84. Contact: Available from IDG Books Worldwide, Inc. 919 E. Hillsdale Blvd., Suite 400, Foster City, CA 94404-2112. (800) 762-2974 or (416) 293-8464. Website: www.idgbooks.com. PRICE: $19.99 plus shipping and handling. ISBN: 076455154X. Summary: This chapter provides people who have diabetes with information on its long term complications, including kidney disease, eye disease, and nerve disease, which are most likely caused by years of high blood glucose levels. Kidney disease, or diabetic nephropathy, is a common complication of diabetes. People who are affected by kidney damage progress through stages of decreasing kidney function over a period of about 20 years. Treatment options include controlling blood glucose, blood pressure, and blood fats; avoiding other damage to the kidneys; and using dialysis if preventive treatment fails. Diabetic eye disease, or diabetic retinopathy, is classified as either background retinopathy and proliferative retinopathy. Laser eye surgery is an excellent treatment option. The nervous system is the third major organ system of the body that is attacked by poorly controlled diabetes. Diabetic nerve disease, or diabetic neuropathy, is usually found in people who have had diabetes the longest. Disorders of the nervous system are classified as disorders associated with loss of sensation, disorders due to loss of motor nerves, and disorders due to loss of autonomic nerves. Other long term complications include heart disease, cardiac autonomic neuropathy, cardiomyopathy, peripheral vascular disease, cerebrovascular disease, diabetic foot disease, and skin diseases. 2 figures.
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Pregnancy and Complications of Type I Diabetes: Maternal and Fetal Implications Source: in LeRoith, D.; Taylor, S.I.; Olefsky, J.M., eds. Diabetes Mellitus: A Fundamental and Clinical Text. Philadelphia, PA: Lippincott-Raven Publishers. 1996. p. 695-710.
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Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740-5184. (800) 777-2295. Fax (301) 824-7390. PRICE: $199.00. ISBN: 0397514565. Summary: This chapter, from a medical textbook on diabetes, explores the maternal and fetal implications of pregnancy in Type I (insulin-dependent, or IDDM) diabetes mellitus. The authors note that, since the introduction of insulin therapy, women with IDDM can conceive, carry a pregnancy to term, and expect to deliver a reasonably healthy, surviving infant. Many of these women, however, have been told that pregnancy may pose a longterm risk to their health. Specifically, physicians often warn these patients that pregnancy can accelerate the progression of retinopathy and nephropathy. The authors of this chapter review current knowledge in this area and conclude that there are very few data with which to counsel these women reliably. Maternal complications include retinopathy, nephropathy, coronary heart disease, neuropathy, and hypoglycemia. Diabetes and obstetric complications covered are pregnancy-induced hypertension, preterm labor, polyhydramnios, and morbidity associated with infection. The authors also consider the effects of diabetes on the embryo, fetus, and neonate, including conception, spontaneous abortion, congenital malformations, minor malformations, preconceptional glycemic control, macrosomia, hypertrophic cardiomyopathy, hypocalcemia and hypomagnesemia, hypoglycemia, polycythemia, hyperbilirubinemia, and respiratory decompensation. 2 tables. 284 references.
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CHAPTER 8. PERIODICALS CARDIOMYOPATHY
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover cardiomyopathy.
News Services and Press Releases One of the simplest ways of tracking press releases on cardiomyopathy 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 “cardiomyopathy” (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 cardiomyopathy. 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 “cardiomyopathy” (or synonyms). The following was recently listed in this archive for cardiomyopathy: •
Pacemaker often needed after septal reduction for obstructive cardiomyopathy Source: Reuters Medical News Date: February 17, 2004
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FDG-PET predicts effectiveness of beta-blockers for cardiomyopathy Source: Reuters Medical News Date: January 29, 2004
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Growth hormone helpful in dilated cardiomyopathy Source: Reuters Industry Breifing Date: January 19, 2004
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Pregnancy-related cardiomyopathy deaths on the rise Source: Reuters Medical News Date: December 10, 2003
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Deaths due to cardiomyopathy in moms-to-be up Source: Reuters Health eLine Date: December 10, 2003
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Microvascular dysfunction predicts long-term prognosis of cardiomyopathy Source: Reuters Medical News Date: September 11, 2003
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Experts advise on diagnosis and treatment of hypertrophic cardiomyopathy Source: Reuters Medical News Date: August 28, 2003
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Women with hypertrophic cardiomyopathy can generally tolerate pregnancy Source: Reuters Medical News Date: July 04, 2003
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Dobutamine, but not nesiritide, arrhythmogenic in cardiomyopathy patients Source: Reuters Industry Breifing Date: June 20, 2003
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Amiodarone, ICDs tied to similar outcomes in patients with cardiomyopathy Source: Reuters Industry Breifing Date: June 04, 2003
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Carvedilol ups survival in dialysis patients with dilated cardiomyopathy Source: Reuters Industry Breifing Date: May 19, 2003
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Pediatric cardiomyopathy more common than previously thought Source: Reuters Medical News Date: April 23, 2003
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Growth hormone ameliorates muscular dystrophy-related cardiomyopathy Source: Reuters Industry Breifing Date: April 16, 2003
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Septal ablation helpful in hypertrophic obstructive cardiomyopathy Source: Reuters Medical News Date: March 24, 2003
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Hypertrophic cardiomyopathy often undiagnosed in African Americans Source: Reuters Medical News Date: March 18, 2003
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New form of familial cardiomyopathy marked by cardiac conduction abnormalities Source: Reuters Medical News Date: March 05, 2003
Periodicals and News
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Cardiomyopathies tied to troponin gene mutations Source: Reuters Medical News Date: February 04, 2003
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Left ventricular thickness alone not linked with sudden death in hypertrophic cardiomyopathy Source: Reuters Medical News Date: January 28, 2003
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Outflow obstruction a key prognostic factor in hypertrophic cardiomyopathy Source: Reuters Medical News Date: January 24, 2003
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Hypertrophic cardiomyopathy increases risk of death during pregnancy Source: Reuters Medical News Date: December 06, 2002
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Maternal mortality is increased in patients with hypertrophic cardiomyopathy Source: Reuters Medical News Date: November 20, 2002
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Surgery superior to alcohol ablation for hypertrophic obstructive cardiomyopathy Source: Reuters Medical News Date: October 10, 2002
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Gene mutation linked to susceptibility to alcoholic cardiomyopathy Source: Reuters Industry Breifing Date: September 02, 2002
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Surgery better than medical therapy for ischemic cardiomyopathy Source: Reuters Industry Breifing Date: August 14, 2002
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Gene transfer improves cardiac function in experimental cardiomyopathy Source: Reuters Industry Breifing Date: July 22, 2002
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Coxsackievirus not tied to cardiomyopathy in children with HIV Source: Reuters Medical News Date: June 24, 2002
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Doppler test identifies patients with hypertrophic cardiomyopathy Source: Reuters Medical News Date: June 03, 2002
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Beta blocker effect in cardiomyopathy linked to changes in gene expression Source: Reuters Industry Breifing Date: May 01, 2002
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Loss of ErbB2 signaling associated with Herceptin leads to cardiomyopathy Source: Reuters Industry Breifing Date: April 30, 2002
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Relatives of patients with cardiomyopathy have similar immunohistology Source: Reuters Medical News Date: February 21, 2002
•
Alcoholic cardiomyopathy can improve without complete abstinence Source: Reuters Medical News Date: February 04, 2002
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Vinculin gene mutation associated with dilated cardiomyopathy Source: Reuters Industry Breifing Date: January 29, 2002
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Echocardiographic criteria defined for new cardiomyopathy Source: Reuters Medical News Date: December 14, 2001
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Vitamin C reverses impaired endothelial function in cardiomyopathy Source: Reuters Medical News Date: December 07, 2001
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Genetic basis and expression of hypertrophic cardiomyopathy clarified Source: Reuters Medical News Date: July 31, 2001
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Immunosuppressive therapy for dilated cardiomyopathy should be reconsidered Source: Reuters Industry Breifing Date: July 06, 2001
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Pregnancy inadvisable for some women after peripartum cardiomyopathy Source: Reuters Medical News Date: May 23, 2001
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Structural protein implicated in development of dilated cardiomyopathy Source: Reuters Medical News Date: May 02, 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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Autoimmunity may play a role in cardiomyopathy Source: Reuters Medical News Date: January 12, 2001
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Long-term survival after peripartum cardiomyopathy better than believed Source: Reuters Medical News Date: December 15, 2000
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Sarcomere protein gene mutations predictive of cardiomyopathy Source: Reuters Medical News Date: December 07, 2000
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Coxsackievirus implicated as cause of idiopathic dilated cardiomyopathy Source: Reuters Medical News Date: November 20, 2000
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Restrictive cardiomyopathy often rapidly lethal in children Source: Reuters Medical News Date: August 28, 2000
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Tachycardia-related cardiomyopathy common in patients with atrial fibrillation Source: Reuters Medical News Date: August 17, 2000
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Simple walk an alternative to exercise testing in some patients with dilated cardiomyopathy Source: Reuters Medical News Date: April 24, 2000
Periodicals and News
•
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Underlying cause of cardiomyopathy predicts long-term survival Source: Reuters Medical News Date: April 13, 2000 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “cardiomyopathy” (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 “cardiomyopathy” (or synonyms). If you know the name of a company that is relevant to cardiomyopathy, 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 “cardiomyopathy” (or synonyms).
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Academic Periodicals covering Cardiomyopathy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to cardiomyopathy. In addition to these sources, you can search for articles covering cardiomyopathy that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. 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 cardiomyopathy. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with cardiomyopathy. 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.).
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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to cardiomyopathy: Anticoagulants •
Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202050.html
Beta-Adrenergic Blocking Agents •
Systemic - U.S. Brands: Betapace; Blocadren; Cartrol; Corgard; Inderal; Inderal LA; Kerlone; Levatol; Lopressor; Normodyne; Sectral; Tenormin; Toprol-XL; Trandate; Visken; Zebeta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202087.html
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; Plendil; Procardia; Procardia XL; Vascor; Verelan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202107.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
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Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to cardiomyopathy by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “cardiomyopathy” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for cardiomyopathy: •
Levocarnitine (trade name: Carnitor) http://www.rarediseases.org/nord/search/nodd_full?code=247
•
Dexrazoxane (trade name: Zinecard) http://www.rarediseases.org/nord/search/nodd_full?code=475
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
•
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
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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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 “cardiomyopathy” (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 49838 286 713 69 434 51340
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 “cardiomyopathy” (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/.
The Genome Project and Cardiomyopathy In the following section, we will discuss databases and references which relate to the Genome Project and cardiomyopathy. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 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. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “cardiomyopathy” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for cardiomyopathy: •
Ataxia, Deafness, and Cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=208750
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Atrial Cardiomyopathy with Heart Block Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=108770
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Cardiomyopathy Associated with Myopathy and Sudden Death Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=212130
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Cardiomyopathy, Congestive, with Hypergonadotropic Hypogonadism Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=212112
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Cardiomyopathy, Dilated, 1a Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115200
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Cardiomyopathy, Dilated, 1b Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600884
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Cardiomyopathy, Dilated, 1c Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601493
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Cardiomyopathy, Dilated, 1d Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601494
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Cardiomyopathy, Dilated, 1e Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601154
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Cardiomyopathy, Dilated, 1f Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602067
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Cardiomyopathy, Dilated, 1g Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604145
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Cardiomyopathy, Dilated, 1h Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604288
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Cardiomyopathy, Dilated, 1i Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604765
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Cardiomyopathy, Dilated, 1j Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605362
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Cardiomyopathy, Dilated, 1k Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605582
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Cardiomyopathy, Dilated, 1l Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606685
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Cardiomyopathy, Dilated, 1m Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607482
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Cardiomyopathy, Dilated, 1n Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607487
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•
Cardiomyopathy, Dilated, 3a Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300069
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Cardiomyopathy, Dilated, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=212110
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Cardiomyopathy, Dilated, with Quadriceps Myopathy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607920
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Cardiomyopathy, Dilated, with Woolly Hair and Keratoderma Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605676
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Cardiomyopathy, Dilated, X-linked Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=302045
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Cardiomyopathy, Familial Hypertrophic Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=192600
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Cardiomyopathy, Familial Hypertrophic, 2 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115195
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Cardiomyopathy, Familial Hypertrophic, 3 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115196
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Cardiomyopathy, Familial Hypertrophic, 4 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115197
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Cardiomyopathy, Familial Hypertrophic, 5 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115198
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Cardiomyopathy, Familial Hypertrophic, with Wolff-parkinson-white Syndrome Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600858
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Cardiomyopathy, Familial Restrictive Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115210
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Cardiomyopathy, Fatal Fetal, due to Myocardial Calcification Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606163
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Cardiomyopathy, Idiopathic Dilated, Mitochondrial Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=510000
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Cardiomyopathy, Infantile Histiocytoid Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=500000
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Cardiomyopathy-hypogonadism-collagenoma Syndrome Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=115250
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Cataract and Cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=212350
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Encephalopathy, Axonal, with Necrotizing Myopathy, Cardiomyopathy, and Cataracts Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=225740
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Hypertaurinuric Cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=145350
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Lipoatrophy with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy, and Leukomelanodermic Papules Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=608056
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Mental Retardation, Scapuloperoneal Muscular Dystrophy, and Cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=309660
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Microcephaly-cardiomyopathy Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=251220
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Progressive External Ophthalmoplegia with Severe Cardiomyopathy, Autosomal Recessive Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601779
Lethal
Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
•
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned
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baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html •
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
•
Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the
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drop box next to “Search.” Enter “cardiomyopathy” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “cardiomyopathy” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 cardiomyopathy 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 cardiomyopathy. 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 cardiomyopathy. 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 “cardiomyopathy”:
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Guides on cardiomyopathy Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html
•
Other guides Circulatory Disorders http://www.nlm.nih.gov/medlineplus/circulatorydisorders.html Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Heart Diseases--Prevention http://www.nlm.nih.gov/medlineplus/heartdiseasesprevention.html Heart Valve Diseases http://www.nlm.nih.gov/medlineplus/heartvalvediseases.html
Within the health topic page dedicated to cardiomyopathy, the following was listed: •
General/Overviews Cardiomyopathy Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4468 Cardiomyopathy Source: Texas Heart Institute http://www.tmc.edu/thi/myopathy.html
•
Diagnosis/Symptoms Echocardiogram Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HB00012 Electrocardiogram (EKG or ECG) Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3005172 Evaluation and Diagnosis Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/evaluation.htm How Is Hypertrophic Cardiomyopathy Diagnosed? Source: Hypertrophic Cardiomyopathy Association http://www.4hcm.org/diagnosis/index.php Signs and Symptoms Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/signs.htm
Patient Resources
What Are Holter, Event and Transtelephonic Monitors? Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3005149 •
Treatment Living with Hypertrophic Cardiomyopathy and Treatments Source: Hypertrophic Cardiomyopathy Association http://www.4hcm.org/treatment/index.php Treatment and Medical Management Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/treatment.htm
•
Nutrition Handling Feeding and Diet Issues Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/feeding.htm
•
Coping Dealing Psychologically with the Disease Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/psych.htm Dealing with Developmental Delays Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/develop.htm Post-Adolescent Issues in the Future Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/post.htm Special Travel Precautions Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/travel.htm Working with the School Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/school.htm
•
Specific Conditions/Aspects Dilated Cardiomyopathy Source: Texas Heart Institute http://www.tmc.edu/thi/dilated.html Familial Dilated Cardiomyopathy http://circ.ahajournals.org/cgi/reprint/108/17/e118.pdf Myocardium and Myocarditis Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4729
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Restrictive Cardiomyopathy Source: Texas Heart Institute http://www.tmc.edu/thi/restrict.html What Is Hypertrophic Cardiomyopathy (HCM)? Source: Hypertrophic Cardiomyopathy Association http://www.4hcm.org/overview/index.php •
Children Overview of Pediatric Cardiomyopathy Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/overview.htm Understanding Pediatric Cardiomyopathy Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/description.htm
•
From the National Institutes of Health Facts about Cardiomyopathy Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/heart/other/cardiomy.htm
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Law and Policy Family and Medical Leave Act Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/family.htm Financial Assistance and Insurance Coverage Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/financial.htm
•
Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/ Hypertrophic Cardiomyopathy Association http://www.4hcm.org/home.php National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/
•
Research Causes of Cardiomyopathy Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/causes.htm
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Pediatric Cardiomyopathy Research Progress to Date Source: Children's Cardiomyopathy Foundation http://www.childrenscardiomyopathy.org/main/progress.htm 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 cardiomyopathy. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
Associations and Cardiomyopathy The following is a list of associations that provide information on and resources relating to cardiomyopathy: •
Cardiomyopathy Association Telephone: 0144(192) 324-9977 Fax: 0144(192) 324-9987
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Web Site: http://www.cardiomyopathy.org Background: The Cardiomyopathy Association is an international not-for-profit selfhelp organization dedicated to providing information and support to individuals affected by cardiomyopathy, their family members, and medical professionals. Cardiomyopathy is a general diagnostic term indicating a primary noninflammatory disease of the heart muscle (myocardium) that is often due to unknown causes. Established in 1989 and consisting of 1,000 members throughout the world, the Cardiomyopathy Association publishes informational brochures on different types of cardiomyopathy. Titles include 'Dilated Cardiomyopathy,' 'Hypertrophic Cardiomyopathy,' and 'Arrhythmogenic Right Ventricular Cardiomyopathy.' The Association also offers videotapes on these topics. In addition to disseminating information, the Association also provides counseling to affected individuals and their family members and endeavors to open the lines of communication between affected individuals and families through an international networking program. •
Children's Cardiomyopathy Foundation Telephone: (201) 227-8852 Fax: (201) 227-7016 Email:
[email protected] Web Site: www.childrenscardiomyopathy.org Background: The Children s Cardiomyopathy Foundation (C.C.F.) was established in 2002 by a parent who lost two young children to cardiomyopathy, a rare and underdiagnosed heart condition. C.C.F. is a non-profit, tax-exempt organization dedicated to accelerating the search for a cause and cure for pediatric cardiomyopathy. Run entirely by volunteers and guided by a medical advisory board, C.C.F. supports critical scientific and medical research into the genetic cause, early detection and effective treatment of this chronic disease. In addition, C.C.F. promotes physician education, public awareness, patient support, and advocacy for affected children and their families. C.C.F. provides a pamphlet, family directory and website with detailed information (medical information, coping and healing tips, resource links, and discussion forum) on the disease. Relevant area(s) of interest: Cardiomyopathy
•
Hypertrophic Cardiomyopathy Association of America Telephone: (973) 983-7429 Toll-free: (877) 329-4262 Fax: (973) 983-7489 Email:
[email protected] Web Site: http://www.4hcm.org Background: The Hypertrophic Cardiomyopathy Association of America is a national self-help organization dedicated to providing information and support to individuals with hypertrophic cardiomyopathy (HCM) and family members. HCM is a primary noninflammatory disease of the heart muscle characterized by enlargement of the lower left chamber of the heart (left ventricle) and of the fibrous partition dividing the two ventricles (interventricular septum). This results in obstruction of outflow of blood from the ventricle and reduced cardiac output. The organization provides information to the medical community, acts as a referral service for affected individuals and family
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members, offers networking services, promotes and supports research, and publishes a regular newsletter entitled 'HCMA News.'. •
Montgomery Heart Foundation for Cardiomyopathy Telephone: (410) 254-6370 Fax: (410) 254-6379 Email:
[email protected] Web Site: www.hopkinsmedicine.org/cardiomyopathy/ Background: The Montgomery Heart Foundation for Cardiomyopathy is a not-for-profit organization dedicated to providing private funding to support genetic research for familial cardiomyopathy and raising awareness of the disease to help promote the advancement of a cure. Cardiomyopathy is a term used to describe a heterogeneous group of disorders causing primary heart muscle dysfunction in both men and women, often leading to heart failure or life-threatening complications. Established in 1993, the Foundation provides direct financial support for research studies focusing on the cause and treatment of cardiomyopathies; creates a constituency for cardiomyopathy and makes the needs and interests of this known to researchers, clinicians, and the general public; facilitates the flow of information between researchers, clinicians, and affected individuals about new developments and breakthroughs; informs the general public about this disease; and offers up-to-date information to affected individuals and their families and helps them to understand what it means to have this disease.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to cardiomyopathy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with cardiomyopathy. 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 cardiomyopathy. 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/.
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Simply type in “cardiomyopathy” (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 “cardiomyopathy”. 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 “cardiomyopathy” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “cardiomyopathy” (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.25
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
25
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)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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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/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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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/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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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/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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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
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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
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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/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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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
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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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
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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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/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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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
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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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
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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
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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
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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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
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on cardiomyopathy: •
Basic Guidelines for Cardiomyopathy Cardiomyopathy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001105.htm
•
Signs & Symptoms for Cardiomyopathy Abdominal swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003122.htm Breath sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003323.htm Change in mental status Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm
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Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Decreased alertness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Decreased amount of urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Heart sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003266.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm High bloodpressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Irregular heartbeat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Lightheadedness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Need to urinate at night Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Palpitations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm
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Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Swelling of legs Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm Syncope Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm •
Diagnostics and Tests for Cardiomyopathy Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Blood Chemistries Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Chest CT scan Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003788.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm CK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm Complete blood count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Computerized tomography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Coronary Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003876.htm Coronary Risk Profile Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003491.htm CPK isoenzymes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003504.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm
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Heart Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003873.htm Heart biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003873.htm LDH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003471.htm LDH isoenzymes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003499.htm Magnetic resonance imaging Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003335.htm MRI of chest Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003794.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •
Surgery and Procedures for Cardiomyopathy Heart transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003003.htm
•
Background Topics for Cardiomyopathy Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Relieved by Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002288.htm
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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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CARDIOMYOPATHY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] 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] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Actomyosin: A protein complex of actin and myosin occurring in muscle. It is the essential contractile substance of muscle. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different
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from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] 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] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH]
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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, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Aldose Reductase Inhibitor: A class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes. Aldose reductase is an enzyme that is normally present in the eye and in many other parts of the body. It helps change glucose (sugar) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Drugs that prevent or slow (inhibit) the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by
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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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [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] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] 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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This
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is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [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 channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amrinone: A positive inotropic cardiotonic agent with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell. Its therapeutic use in congestive heart or left ventricular failure is associated with significant increases in the cardiac index, reductions in pulmonary capillary wedge pressure and systemic vascular resistance, and little or no change in mean arterial pressure. One of its more serious side effects is thrombocytopenia in some patients. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] 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] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU]
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Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [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] Anergy: Absence of immune response to particular substances. [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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH]
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Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] 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] 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] Antidepressant: A drug used to treat depression. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH]
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Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] 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] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arrhythmogenic: Producing or promoting arrhythmia. [EU] Arrhythmogenic Right Ventricular Dysplasia: A weakening of the right ventricle that results in the back up of blood in the venous system, liver, gastrointestinal tract, and extremities. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH]
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Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [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]
Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] 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] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic Eczema: Generic term for acute or chronic inflammatory conditions of the skin, typically erythematous, edematous, papular, vesicular, and crusting; often accompanied by sensations of itching and burning. [NIH] 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]
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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] Attenuated: Strain with weakened or reduced virulence. [NIH] Auscultation: Act of listening for sounds within the body. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] 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] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Baclofen: A GABA derivative that is a specific agonist at GABA-B receptors. It is used in the treatment of spasticity, especially that due to spinal cord damage. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] 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 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]
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Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [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] Beer: An alcoholic beverage usually made from malted cereal grain (as barley), flavored with hops, and brewed by slow fermentation. [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] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [NIH]
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Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological Phenomena: Biological functions and activities at the organic and molecular levels in humans, animals, microorganisms, and plants. For biochemical and metabolic processes, biochemical phenomena is available. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [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] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [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] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the
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heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] 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 Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Brachiocephalic Veins: Large veins on either side of the root of the neck formed by the junction of the internal jugular and subclavian veins. They drain blood from the head, neck, and upper extremities, and unite to form the superior vena cava. [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 Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain stem; and cerebellum. [NIH]
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Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bundle-Branch Block: A form of heart block in which one ventricle is excited before the other because of absence of conduction in one of the branches of the bundle of His. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [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 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, 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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH]
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Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] 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] 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] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiac catheterization: A procedure in which a thin, hollow tube is inserted into a blood vessel. The tube is then advanced through the vessel into the heart, enabling a physician to study the heart and its pumping activity. [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] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomegaly: Hypertrophy or enlargement of the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiomyopathy, Alcoholic: Cardiomyopathy resulting from: (1) a toxic effect of alcohol on the myocardium; (2) thiamine deficiency due to malnutrition in alcoholics; or (3) a toxic effect of cobalt additives in beer in heavy beer drinkers. This disease is usually manifested by dyspnea and palpitations with cardiomegaly and congestive heart failure. [NIH]
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Cardiomyopathy, Hypertrophic: A myocardial disease characterized by hypertrophy, involving mainly the interventricular septum, interfering with left ventricular emptying. [NIH]
Cardiomyoplasty: A surgical procedure that involves detaching one end of a back muscle and attaching it to the heart. An electric stimulator causes the muscle to contract to pump blood from the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [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 Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. [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] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of
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occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [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] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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]
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Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [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] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [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] 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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] 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]
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Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chordae Tendineae: The tendinous cords that connect each cusp of the two atrioventricular valves to appropriate papillary muscles in the heart ventricles, preventing the valves from reversing themselves when the ventricles contract. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [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 lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [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]
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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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [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] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [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] 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] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [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] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [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
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occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the
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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] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [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] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contractile Proteins: Proteins which participate in contractile processes. They include muscle proteins as well as those found in other cells and tissues. In the latter, these proteins participate in localized contractile events in the cytoplasm, in motile activity, and in cell aggregation phenomena. [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] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled 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]
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Contusion: A bruise; an injury of a part without a break in the skin. [EU] 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] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary 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] 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] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cost-benefit: A quantitative technique of economic analysis which, when applied to radiation practice, compares the health detriment from the radiation doses concerned with the cost of radiation dose reduction in that practice. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial
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tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crystallins: A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [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] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with
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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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [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]
De novo: In cancer, the first occurrence of cancer in the body. [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] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Defibrillation: The act to arrest the fibrillation of (heart muscle) by applying electric shock across the chest, thus depolarizing the heart cells and allowing normal rhythm to return. [EU] 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] Dementia: An acquired organic mental disorder with loss of intellectual abilities of
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sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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] 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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexrazoxane: A drug used to protect the heart from the toxic effects of anthracycline drugs such as doxorubicin. It belongs to the family of drugs called chemoprotective agents. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina
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and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [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] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diastolic pressure: The lowest pressure to which blood pressure falls between contractions of the ventricles. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] 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] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [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
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objects. [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] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] 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] Dobutamine: A beta-2 agonist catecholamine that has cardiac stimulant action without evoking vasoconstriction or tachycardia. It is proposed as a cardiotonic after myocardial infarction or open heart surgery. [NIH] 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] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [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 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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH]
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Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] 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] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elastomers: A generic term for all substances having the properties of natural, reclaimed, vulcanized, or synthetic rubber, in that they stretch under tension, have a high tensile strength, retract rapidly, and recover their original dimensions fully. [NIH] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [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
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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] 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] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [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] 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] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emetic: An agent that causes vomiting. [EU] Emetine: The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein syntheis in eucaryotic but not prokaryotic cells. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [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] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a
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primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] 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, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enoximone: 1,3-Dihydro-4-methyl-5-(4-(methylthio)benzoyl)-2H-imidazol-2-one. A selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with congestive heart failure. [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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Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]
for
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 Repression: The interference in synthesis of an enzyme due to the elevated level of an effector substance, usually a metabolite, whose presence would cause depression of the gene responsible for enzyme synthesis. [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] Epidemiological: Relating to, or involving epidemiology. [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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epidural block: An injection of an anesthetic drug into the space between the wall of the spinal canal and the covering of the spinal cord. [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] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH]
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Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked
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to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] 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] 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] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [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 non-
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identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] 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] 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] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [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] Fold: A plication or doubling of various parts of the body. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [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] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [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 calories. [NIH]
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Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fura-2: A fluorescent calcium chelating agent which is used to study intracellular calcium in many tissues. The fluorescent and chelating properties of Fura-2 aid in the quantitation of endothelial cell injury, in monitoring ATP-dependent calcium uptake by membrane vesicles, and in the determination of the relationship between cytoplasmic free calcium and oxidase activation in rat neutrophils. [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] GABA Agonists: Drugs that bind to and activate GABA receptors. [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gait: Manner or style of walking. [NIH] Gait Ataxia: Impairment of the ability to coordinate the movements required for normal ambulation which may result from impairments of motor function or sensory feedback. This condition may be associated with brain diseases (including cerebellar diseases and basal ganglia diseases); spinal cord diseases; or peripheral nervous system diseases. [NIH] Galactitol: A naturally occurring product of plants obtained following reduction of galactose. It appears as a white crystalline powder with a slight sweet taste. It may form in excess in the lens of the eye in galactosemia, a deficiency of galactokinase. [NIH] Galactokinase: An enzyme that catalyzes reversibly the formation of galactose 1-phosphate and ADP from ATP and D-galactose. Galactosamine can also act as the acceptor. A deficiency of this enzyme results in galactosemia. EC 2.7.1.6. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallopamil: Coronary vasodilator that is an analog of iproveratril (verapamil) with one more methoxy group on the benzene ring. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] 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 Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac,
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gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [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]
Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an
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increased risk for developing a specific disease or disorder. [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] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH]
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Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [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] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonads: The gamete-producing glands, ovary or testis. [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] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH]
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Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] 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] 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] Heart Catheterization: Procedure which includes placement of catheter, recording of intracardiac and intravascular pressure, obtaining blood samples for chemical analysis, and cardiac output measurement, etc. Specific angiographic injection techniques are also involved. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]
Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heart Ventricle: The lower right and left chambers of the heart. The right pumps venous blood into the lungs and the left pumps oxygenated blood into the systemic arterial circulation. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [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]
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Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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] 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] Hemoglobinuria: The presence of free hemoglobin in the urine. [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] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [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] Hepatomegaly: Enlargement of the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [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]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygote: An individual having different alleles at one or more loci in homologous
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chromosome segments. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] Hormonal: Pertaining to or of the nature of a hormone. [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] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]
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Hydrops Fetalis: Edema of the entire body due to abnormal accumulation of serous fluid in the tissues, associated with severe anemia and occurring in fetal erythroblastosis. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperaldosteronism: Aldosteronism. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] 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] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] 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] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] 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] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH]
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Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [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] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]
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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] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [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] Incompetence: Physical or mental inadequacy or insufficiency. [EU] 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] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called
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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] 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] Instillation: . [EU] 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] Insulin-like: Muscular growth factor. [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-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] Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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
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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] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] 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] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [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] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ipecac: A syrup made from the dried rhizomes of two different species, Cephaelis ipecacuanha and C. acuminata, belonging to the Rubiaciae family. They contain emetine, cephaeline, psychotrine and other isoquinolines. Ipecac syrup is used widely as an emetic acting both locally on the gastric mucosa and centrally on the chemoreceptor trigger zone. [NIH]
Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU]
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Islet: Cell producing insulin in pancreas. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [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] 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] 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] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] 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
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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] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Leishmania: A genus of flagellate protozoa comprising several species that are pathogenic for humans. Organisms of this genus have an amastigote and a promastigote stage in their life cycles. As a result of enzymatic studies this single genus has been divided into two subgenera: Leishmania leishmania and Leishmania viannia. Species within the Leishmania leishmania subgenus include: L. aethiopica, L. arabica, L. donovani, L. enrietti, L. gerbilli, L. hertigi, L. infantum, L. major, L. mexicana, and L. tropica. The following species are those that compose the Leishmania viannia subgenus: L. braziliensis, L. guyanensis, L. lainsoni, L. naiffi, and L. shawi. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [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]
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Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH]
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Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobectomy: The removal of a lobe. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [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] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU]
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Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammogram: An x-ray of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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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Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] 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] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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]
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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] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] 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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Motors: Protein based machines that are involved in or cause movement such as
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the rotary devices (flagellar motor and the F1 ATPase) or the devices whose movement is directed along cytoskeletal filaments (myosin, kinesin and dynein motor families). [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [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] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Multivariate Analysis: A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [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 filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are
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characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] 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] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] 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]
Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [EU] 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] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH]
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Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [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] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] 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 bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [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] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH]
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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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH] Nicorandil: A derivative of the niacinamide that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] 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] 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 Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14.
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Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] 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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] 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] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH]
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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 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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] 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] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging atpase. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [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] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH]
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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 Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] 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] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] 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] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papillary Muscles: Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae. [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] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [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
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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] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Satisfaction: The degree to which the individual regards the health care service or product or the manner in which it is delivered by the provider as useful, effective, or beneficial. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] 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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [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] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological
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systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Perivascular: Situated around a vessel. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top
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of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipase C: An enzyme found in the alpha-toxin of Clostridium welchii and other strains of clostridia and bacilli. It hydrolyzes glycerophosphatidates with the formation of 1,2-diacylglycerol and a phosphorylated nitrogenous base such as choline. EC 3.1.4.3. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylating: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
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] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH]
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Pilot study: The initial study examining a new method or treatment. [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] 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 Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
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Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polyhydramnios: Excess of amniotic fluid greater than 2,000 ml. It is a common obstetrical complication whose major causes include maternal diabetes, chromosomal disorders, isoimmunological disease, congenital abnormalities, and multiple gestations. [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] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] 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] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Porosity: Condition of having pores or open spaces. This often refers to bones, bone implants, or bone cements, but can refer to the porous state of any solid substance. [NIH] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [NIH]
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Post partum: After childbirth, or after delivery. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Postural: Pertaining to posture or position. [EU] 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] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [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] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [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
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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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [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] Proliferative Retinopathy: A disease of the small blood vessels of the retina of the eye. [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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [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] 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] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in
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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 B: Physiologically active prostaglandins found in many tissues and organs. They are potent pressor substances and have many other physiological activities. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [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] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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]
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Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [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] 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] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
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]
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Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
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] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] 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] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radioisotope Renography: Graphic tracing over a time period of radioactivity measured externally over the kidneys following intravenous injection of a radionuclide which is taken up and excreted by the kidneys. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radionuclide Angiography: The measurement of visualization by radiation of any organ after a radionuclide has been injected into its blood supply. It is used to diagnose heart, liver, lung, and other diseases and to measure the function of those organs, except renography, for which radioisotope renography is available. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that
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the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [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] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] 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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Repressor Proteins: Proteins which are normally bound to the operator locus of an operon, thereby preventing transcription of the structural genes. In enzyme induction, the substrate of the inducible enzyme binds to the repressor protein, causing its release from the operator and freeing the structural genes for transcription. In enzyme repression, the end product of the enzyme sequence binds to the free repressor protein, the resulting complex then binds to the operator and prevents transcription of the structural genes. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Restrictive cardiomyopathy: Heart muscle disease in which the muscle walls become stiff and lose their flexibility. [NIH] 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
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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] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [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] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhythmicity: Regular periodicity. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU]
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Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcomere: The repeating structural unit of a striated 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] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH]
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Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] 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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH]
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Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [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] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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] 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] 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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the
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brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] 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 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] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle
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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] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squalene Synthetase: Catalyzes the rearrangement and reduction of the cyclopropane compound, presqualene pyrophosphate to form squalene, with NADPH as the coenzyme. [NIH]
Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body.
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[NIH]
Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Steatosis: Fatty degeneration. [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] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [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] Steroids: Drugs used to relieve swelling and inflammation. [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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] 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]
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Substrate: A substance upon which an enzyme acts. [EU] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superior vena cava: Vein which returns blood from the head and neck, upper limbs, and thorax. It is formed by the union of the two brachiocephalic veins. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [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]
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Symphysis: A secondary cartilaginous joint. [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] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systole: Period of contraction of the heart, especially of the ventricles. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic heart failure: Inability of the heart to contract with enough force to pump adequate amounts of blood through the body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [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] Teratogenicity: The power to cause abnormal development. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased
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synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [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] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
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] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] 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] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] 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] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic
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number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]
Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH]
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Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trimetazidine: A vasodilator used in angina of effort or ischemic heart disease. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Troponin C: One of the three polypeptide chains that make up the troponin complex of skeletal muscle. It is a calcium-binding protein. [NIH] Troponin T: One of the three polypeptide chains that make up the troponin complex. It is a cardiac-specific protein that binds to tropomyosin. It is released from only damaged or injured heart tissue and cells. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [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]
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Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] 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] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [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] Urethane: Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen. [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 Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]
Urinate: To release urine from the bladder to the outside. [NIH]
Dictionary 351
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vasa Nervorum: Blood vessels supplying the nerves. [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] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] 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] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH]
352
Cardiomyopathy
Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]
Ventricular Remodeling: The geometric and structural changes that the ventricle undergoes, usually following myocardial infarction. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle. [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] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [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] Welchii: A genus of anerobic spore-forming bacteria of the family Bacillaceae. [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]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border
Dictionary 353
of the fifth thoracic vertebra. [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] World Health: The concept pertaining to the health status of inhabitants of the world. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [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]
355
INDEX 3 3-dimensional, 36, 92, 147, 265, 333 A Abdomen, 265, 277, 282, 296, 304, 309, 310, 314, 325, 327, 343, 344, 347, 352 Abdominal, 259, 265, 266, 308, 314, 325, 327 Abducens, 265, 268 Aberrant, 13, 59, 69, 219, 265 Ablate, 265, 281 Ablation, 17, 73, 79, 80, 90, 91, 98, 102, 109, 111, 118, 145, 146, 224, 225, 265 Abscess, 265, 340 Acceptor, 265, 300, 314, 325, 349 Acetylcholine, 265, 283, 322 Acidosis, 48, 265, 290 Acquired Immunodeficiency Syndrome, 59, 140, 146, 265 Actin, 19, 24, 34, 38, 39, 49, 55, 58, 61, 64, 77, 160, 202, 265, 318, 319, 320, 349 Actinin, 193, 265, 293 Action Potentials, 36, 265 Actomyosin, 10, 215, 265 Acyl, 63, 68, 265, 317 Adaptability, 265, 281, 282 Adaptation, 15, 30, 39, 266, 329 Adenine, 173, 210, 266, 335 Adenosine, 76, 176, 199, 266, 269, 273, 308, 313, 328 Adenovirus, 201, 266 Adenylate Cyclase, 266, 299 Adipocytes, 266, 286, 313 Adipose Tissue, 6, 63, 180, 266 Adjunctive Therapy, 41, 266 Adjustment, 172, 217, 266 Adjuvant, 50, 266, 299, 301 Adolescence, 152, 266 Adrenal Cortex, 266, 268, 337 Adrenal Glands, 266, 269 Adrenal Medulla, 266, 281, 296, 323 Adrenergic, 7, 9, 14, 26, 35, 45, 54, 88, 131, 190, 209, 210, 230, 266, 268, 271, 296, 317, 345 Adrenergic beta-Antagonists, 266, 271 Adverse Effect, 25, 50, 155, 173, 184, 190, 266, 341 Aerobic, 173, 266, 297, 318, 350 Afferent, 60, 163, 267, 313, 328
Affinity, 10, 61, 210, 267, 273, 317, 342 Agar, 267, 329 Age of Onset, 267, 350 Agonist, 6, 21, 164, 187, 199, 267, 274, 292, 308, 319 Airway, 267, 342 Akinesia, 179, 267 Alanine, 51, 267 Albumin, 267, 317 Aldehydes, 267, 353 Aldose Reductase Inhibitor, 162, 163, 164, 175, 176, 187, 188, 199, 204, 205, 267 Aldosterone, 183, 184, 196, 267 Alertness, 260, 268 Algorithms, 5, 268, 276 Alimentary, 268 Alkaline, 27, 265, 268, 278 Alkaline Phosphatase, 27, 268 Alkaloid, 268, 275, 294 Alleles, 53, 58, 177, 268, 305 Allergen, 268, 290 Allograft, 166, 268 Allopurinol, 64, 268 Alpha Particles, 268, 335 Alpha-1, 268, 328 Alprenolol, 268, 317 Alternans, 13, 106, 115, 116, 268 Alternative medicine, 227, 268 Alternative Splicing, 268, 333 Ameliorated, 46, 268 Ameliorating, 173, 204, 268 Amenorrhea, 268, 330 Amino Acid Sequence, 166, 268, 271, 297, 301 Amino Acid Substitution, 51, 269 Amino Acids, 160, 203, 268, 269, 270, 301, 317, 326, 330, 333, 338, 340, 345, 348, 349, 350 Amiodarone, 72, 88, 224, 269 Amlodipine, 100, 192, 269 Amniotic Fluid, 269, 330 Ampulla, 74, 269, 295 Amrinone, 190, 269, 318 Amylase, 83, 269 Amyloid, 51, 182, 187, 220, 269 Amyloidosis, 51, 70, 107, 108, 220, 269 Anaesthesia, 122, 269, 309 Anal, 18, 64, 269, 315, 319
356
Cardiomyopathy
Analog, 16, 48, 269, 299, 300, 323 Analogous, 55, 269, 349 Analytes, 270, 345 Anaphylatoxins, 270, 285 Anatomical, 24, 46, 168, 174, 175, 178, 194, 209, 270, 274, 286, 309, 339 Anemia, 4, 32, 176, 177, 191, 214, 217, 218, 243, 270, 284, 307, 347, 353 Anergy, 270, 345 Anesthesia, 103, 108, 145, 155, 267, 270, 288, 332 Anesthetics, 270, 296 Aneurysm, 112, 270, 300, 351 Angina, 9, 41, 77, 151, 191, 192, 196, 266, 269, 270, 271, 312, 317, 322, 323, 349 Angina Pectoris, 9, 77, 191, 192, 196, 266, 269, 270, 312, 317 Anginal, 268, 270, 271, 322 Angiogenesis, 10, 270, 316 Angiogram, 148, 154, 270 Angiotensin converting enzyme inhibitor, 199, 270 Angiotensin-Converting Enzyme Inhibitors, 270, 271 Angiotensinogen, 32, 196, 270, 336, 337 Animal model, 5, 11, 13, 20, 27, 30, 34, 42, 46, 48, 59, 60, 62, 66, 162, 170, 173, 174, 177, 181, 183, 218, 270 Anions, 267, 271, 311, 345 Annealing, 271, 330 Anomalies, 271, 346 Anovulation, 271, 330 Antagonism, 271, 291 Anthracycline, 271, 289, 290, 308 Antianginal, 269, 271, 298 Antiarrhythmic, 13, 269, 271, 298 Antibacterial, 271, 343 Antibiotic, 134, 271, 289, 292, 308, 343, 346 Antibodies, 73, 198, 209, 210, 219, 271, 274, 304, 306, 308, 315, 329 Antibody, 49, 169, 203, 267, 271, 284, 304, 306, 308, 309, 316, 319, 335, 343, 345 Anticoagulant, 271, 333 Antidepressant, 58, 271 Antidiabetic, 199, 204, 271 Antidiabetic Agent, 199, 204, 271 Antigen, 32, 50, 166, 267, 271, 285, 306, 307, 308, 309, 316, 345 Antigen-Antibody Complex, 271, 285 Antihypertensive, 4, 172, 176, 268, 271, 299, 322 Antihypertensive Agents, 172, 176, 271
Anti-infective, 272, 306, 311 Anti-inflammatory, 184, 272, 302, 331 Antimicrobial, 186, 272 Antineoplastic, 272, 292, 299, 302, 317, 322, 325, 350 Antineoplastic Agents, 272, 322 Antioxidant, 48, 49, 120, 123, 124, 176, 272, 273, 325 Antiproliferative, 272, 310 Antispasmodic, 164, 272 Antiviral, 48, 169, 272, 310 Anuria, 272, 312 Anus, 269, 272, 277 Anxiety, 58, 266, 272 Aorta, 181, 204, 206, 207, 272, 304, 308, 351 Aortic Valve, 75, 175, 207, 272 Apnea, 212, 272 Apoptosis, 6, 9, 28, 32, 46, 49, 56, 65, 66, 76, 95, 113, 193, 272, 280 Applicability, 8, 191, 272 Aqueous, 272, 275, 289, 306, 313 Arachidonic Acid, 184, 272, 314, 332 Arginine, 48, 51, 270, 272, 322, 350 Aromatic, 272, 317, 328, 344 Arrhythmia, 12, 30, 88, 93, 100, 115, 171, 271, 272, 352 Arrhythmogenic, 12, 35, 73, 74, 77, 87, 92, 96, 108, 130, 214, 224, 250, 272 Arrhythmogenic Right Ventricular Dysplasia, 108, 272 Arterial, 46, 168, 170, 204, 206, 210, 269, 272, 273, 304, 307, 322, 323, 333, 346 Arteriolar, 273, 277, 298, 337 Arterioles, 204, 273, 277, 279, 318, 320, 322, 351 Arteriosus, 273, 334 Arteriovenous, 218, 273, 318 Arteriovenous Fistula, 218, 273 Articular, 220, 273 Ascorbic Acid, 48, 273, 307 Assay, 14, 49, 273 Astrocytes, 273, 305 Asymptomatic, 7, 53, 72, 93, 109, 110, 123, 190, 273 Ataxia, 25, 53, 123, 176, 177, 240, 242, 273, 308, 346 Atopic, 134, 273 Atopic Eczema, 134, 273 ATP, 14, 34, 44, 52, 173, 179, 209, 266, 273, 287, 292, 300, 302, 303, 313, 328, 333, 348 Atrial Fibrillation, 78, 79, 94, 108, 186, 191, 196, 226, 273, 341
Index 357
Atrial Flutter, 191, 196, 273 Atrioventricular, 70, 96, 273, 283, 325, 341, 345 Atrioventricular Node, 273, 345 Atrium, 143, 181, 189, 197, 273, 274, 318, 341, 345, 351 Atrophy, 171, 242, 274, 314 Attenuated, 26, 48, 274, 291 Auscultation, 54, 274 Autoantibodies, 75, 88, 209, 210, 274 Autoantigens, 274 Autoimmune disease, 94, 203, 274 Autoimmunity, 50, 88, 94, 226, 274 Autologous, 117, 274 Autonomic, 4, 60, 74, 103, 151, 218, 220, 265, 274, 300, 323, 327, 342, 345 Autonomic Nervous System, 74, 274, 327, 342, 345 Autonomic Neuropathy, 4, 103, 218, 220, 274 Autopsy, 4, 73, 75, 146, 274 Avian, 54, 274, 288 Axons, 274, 324, 327 B Baclofen, 164, 274 Bacteria, 265, 271, 274, 294, 295, 296, 298, 306, 318, 336, 340, 343, 348, 350, 351, 352 Bacterial Physiology, 266, 274 Bactericidal, 274, 297 Bacteriophage, 274, 329, 348 Basal Ganglia, 273, 275, 277, 300 Basal Ganglia Diseases, 273, 275, 300 Base, 266, 275, 290, 301, 312, 313, 328, 330, 346 Basement Membrane, 162, 167, 219, 275, 297, 313 Basophils, 275, 303, 313 Beer, 275, 279 Benzene, 275, 300 Berberine, 82, 275 Beta blocker, 155, 225, 275 Beta Rays, 275, 294 Beta-pleated, 269, 275 Bilateral, 275, 330 Bile, 275, 300, 301, 312, 314, 346 Bile Acids, 275, 301, 346 Bilirubin, 267, 275, 307 Binding Sites, 54, 275 Biochemical Phenomena, 275, 276 Biogenesis, 48, 276 Biological Phenomena, 57, 276 Biological response modifier, 276, 310
Biological therapy, 276, 304 Biomarkers, 49, 276 Biomolecular, 75, 214, 276, 345 Biopsy, 19, 27, 30, 104, 154, 261, 262, 276, 326 Biosynthesis, 57, 272, 276, 288, 299, 340 Biotechnology, 65, 70, 227, 237, 239, 242, 243, 276 Biphasic, 39, 93, 190, 276 Bivalent, 276, 317 Bladder, 274, 276, 321, 333, 350, 351 Blast phase, 276, 283 Blastocyst, 276, 285, 329 Blood Coagulation, 276, 278, 347 Blood Glucose, 206, 220, 276, 305, 307, 310 Blood Platelets, 276, 341, 347 Blood Volume, 277, 280 Blot, 14, 49, 277 Body Fluids, 276, 277, 278, 292, 342, 350 Body Mass Index, 277, 324 Bone Cements, 277, 330 Bone Marrow, 208, 275, 276, 277, 283, 288, 308, 315, 317, 342, 353 Bone scan, 277, 339 Bowel, 269, 277, 291, 311, 313, 323, 327 Bowel Movement, 277, 291 Brachial, 277, 316 Brachial Plexus, 277, 316 Brachiocephalic Veins, 277, 345 Bradycardia, 186, 277, 341 Bradykinin, 62, 277, 312, 322 Brain Diseases, 277, 300 Branch, 95, 141, 257, 278, 294, 326, 334, 343, 347 Breakdown, 278, 290, 291, 300, 324 Breeding, 41, 278 Bronchi, 278, 296, 348 Bundle-Branch Block, 80, 278 Butyric Acid, 176, 278 Bypass, 15, 278, 320 C Calcification, 41, 241, 278 Calcineurin, 69, 70, 193, 278 Calcium channel blocker, 192, 269, 271, 278, 322, 352 Calcium Channel Blockers, 271, 278, 322 Calcium Channels, 7, 278, 318 Callus, 278, 294 Calmodulin, 12, 193, 278, 279, 299 Calpain, 212, 279 Cannula, 143, 279
358
Cardiomyopathy
Capillary, 162, 204, 210, 219, 269, 277, 279, 302, 351, 352 Capillary Permeability, 277, 279 Carbohydrate, 15, 173, 279, 302, 303, 330 Carbon Dioxide, 180, 279, 289, 300, 329, 337, 351 Carboxy, 39, 43, 279 Carcinogen, 279, 317, 350 Carcinogenic, 275, 279, 310, 332 Cardiac catheterization, 145, 146, 147, 155, 279 Cardiac Output, 12, 24, 47, 48, 95, 165, 171, 175, 209, 210, 250, 279, 304, 344 Cardiogenic, 28, 279 Cardiomegaly, 279 Cardiomyopathy, Alcoholic, 279 Cardiomyopathy, Hypertrophic, 143, 146, 147, 150, 152, 186, 280 Cardiomyoplasty, 172, 178, 280 Cardiopulmonary, 65, 151, 280 Cardiotonic, 269, 280, 291, 292, 318 Cardiotoxic, 49, 280 Cardiotoxicity, 55, 59, 280 Cardiovascular Abnormalities, 7, 167, 280 Cardiovascular Agents, 172, 280 Cardiovascular disease, 18, 32, 34, 37, 48, 52, 60, 62, 167, 184, 195, 203, 208, 217, 218, 280 Cardiovascular System, 7, 18, 30, 40, 62, 162, 196, 274, 280 Cardioversion, 94, 108, 280, 341 Carnitine, 34, 120, 121, 122, 123, 124, 125, 127, 132, 133, 280 Carotene, 280, 337 Carotid Arteries, 204, 280 Carpal Tunnel Syndrome, 212, 280 Case report, 68, 73, 93, 103, 109, 280, 283 Caspase, 49, 65, 280 Catalytic Domain, 193, 280 Cataract, 21, 162, 241, 280 Catecholamine, 281, 292, 327 Catheter Ablation, 103, 281 Catheterization, 48, 143, 146, 148, 154, 155, 281, 311, 320 Catheters, 146, 170, 207, 281 Cathode, 275, 281, 294 Cations, 281, 311 Causality, 55, 281 Cause of Death, 13, 206, 208, 213, 218, 281 Caveolae, 56, 281 Caveolins, 281 Cell Cycle, 28, 40, 281, 288, 304, 334
Cell Death, 11, 25, 28, 32, 48, 49, 203, 272, 281, 321 Cell Differentiation, 41, 281, 341 Cell Division, 192, 242, 274, 281, 282, 304, 316, 318, 329, 332 Cell membrane, 278, 281, 282, 290, 328 Cell Membrane Structures, 281, 282 Cell proliferation, 40, 198, 282, 341 Cell Respiration, 282, 318, 337 Cell Survival, 282, 304 Cerebellar, 273, 282, 300, 336 Cerebellar Diseases, 273, 282, 300 Cerebral, 206, 211, 273, 275, 277, 282, 296, 297, 298, 304 Cerebral Arteries, 206, 282 Cerebrovascular, 153, 169, 173, 204, 220, 275, 278, 280, 282, 322, 346 Cerebrum, 282, 350 Cervical, 277, 282, 304, 316 Character, 174, 178, 270, 282, 289 Chelation, 13, 134, 282 Chelation Therapy, 13, 134, 282 Chemoprotective, 282, 290 Chemoreceptor, 282, 311 Chemotactic Factors, 282, 285 Chest Pain, 52, 121, 141, 142, 145, 146, 147, 152, 187, 200, 282 Chest wall, 154, 282 Cholesterol, 18, 206, 275, 281, 282, 287, 293, 307, 314, 315, 317, 339 Choline, 283, 328 Chordae Tendineae, 283, 325 Choroid, 283, 287, 337 Chromatin, 272, 283, 296, 322 Chromosomal, 283, 330 Chromosome, 27, 29, 38, 65, 177, 283, 306, 314 Chronic Disease, 19, 250, 283, 284 Chronic lymphocytic leukemia, 283 Chronic myelogenous leukemia, 276, 283 Chronic phase, 57, 283 Chronic renal, 220, 283, 330 Chronotropic, 106, 283 Circulatory system, 143, 283 CIS, 14, 53, 283, 337 Citrus, 273, 283 Clamp, 7, 23, 283 Cleave, 62, 283 Clinical Medicine, 15, 283, 331 Clinical study, 283, 286 Clinical trial, 4, 25, 123, 141, 156, 190, 210, 237, 283, 284, 286, 288, 334, 335
Index 359
Cloning, 28, 29, 39, 276, 284 Clot Retraction, 284, 329 Coagulation, 276, 284, 305, 347 Cobalt, 279, 284 Coenzyme, 137, 176, 177, 199, 273, 284, 322, 343 Cofactor, 284, 333, 347 Collagen, 62, 98, 182, 198, 206, 275, 284, 298, 299, 301, 316, 329, 332 Collagen disease, 182, 284 Collapse, 155, 278, 284, 342 Colorectal, 67, 284 Colorectal Cancer, 67, 284 Combination Therapy, 284, 297 Complement, 11, 270, 284, 285, 301 Complementary and alternative medicine, 129, 138, 285 Complementary medicine, 129, 285 Complementation, 57, 285 Computational Biology, 237, 239, 285 Computed tomography, 114, 120, 285, 339 Computerized axial tomography, 285, 339 Computerized tomography, 261, 285 Concentric, 45, 192, 285 Conception, 221, 285, 298 Concomitant, 9, 185, 286 Conduction, 7, 29, 66, 68, 78, 100, 154, 164, 170, 224, 273, 278, 281, 286 Cones, 286, 328, 338 Confounding, 50, 286 Confusion, 286, 350 Congestion, 170, 187, 211, 286 Conjugated, 286, 288 Conjunctiva, 286, 309 Connective Tissue, 162, 182, 273, 277, 284, 286, 299, 300, 301, 317, 327, 338 Connective Tissue Cells, 286 Consciousness, 286, 290, 292 Constitutional, 286, 320 Constriction, 178, 286, 311, 351 Constriction, Pathologic, 286, 351 Consumption, 7, 47, 151, 286, 323, 325 Continuum, 56, 286 Contractile Proteins, 24, 26, 43, 286 Contractility, 7, 9, 12, 27, 43, 46, 48, 113, 174, 178, 213, 270, 286, 293 Contraindications, ii, 286 Contralateral, 268, 286, 336 Control group, 151, 286 Controlled clinical trial, 4, 51, 286 Contusion, 195, 287 Conus, 287, 334
Conventional therapy, 124, 287 Conventional treatment, 287 Coronary Angiography, 18, 145, 217, 261, 287 Coronary Arteriosclerosis, 195, 287, 320 Coronary Circulation, 47, 270, 287, 323 Coronary Disease, 141, 146, 153, 154, 167, 246, 287 Coronary heart disease, 78, 172, 221, 280, 287 Coronary Thrombosis, 287, 317, 320 Coronary Vessels, 167, 287 Cortex, 273, 277, 282, 287, 297, 298, 324, 336 Cortical, 19, 287, 297, 340, 346 Corticosteroids, 184, 287, 302, 331 Cortisone, 287, 331 Cost-benefit, 52, 287 Cranial, 287, 304, 324, 327 Creatine, 56, 105, 287 Creatine Kinase, 56, 287 Creatinine, 27, 287, 288, 312 Crystallins, 20, 288 Cultured cells, 40, 288 Curare, 288, 319 Curative, 288, 322, 338, 347 Cutaneous, 57, 288, 313, 315 Cyclic, 189, 190, 266, 279, 288, 299, 304, 322, 328, 333, 340 Cyclin, 40, 288 Cyclosporine, 147, 288 Cystathionine beta-Synthase, 288, 307 Cysteine, 67, 279, 288, 345 Cystine, 288 Cytochrome, 47, 49, 65, 288, 325 Cytokine, 19, 41, 75, 82, 83, 106, 123, 166, 288, 310, 326 Cytomegalovirus, 169, 288 Cytoplasm, 193, 272, 275, 281, 286, 289, 296, 303, 317, 320, 322, 338, 339, 352 Cytoskeletal Proteins, 20, 39, 55, 279, 289, 293 Cytoskeleton, 20, 21, 59, 202, 289, 318 Cytotoxic, 16, 166, 289, 341 D Data Collection, 24, 148, 289 Databases, Bibliographic, 237, 289 Daunorubicin, 289, 292 De novo, 180, 289 Decarboxylation, 289, 306, 319 Decidua, 289, 329 Decompensation, 221, 289
360
Cardiomyopathy
Decompression, 68, 289 Decompression Sickness, 289 Defibrillation, 135, 186, 289 Degenerative, 6, 8, 124, 133, 177, 182, 287, 289, 305, 338 Deletion, 11, 33, 66, 162, 177, 183, 272, 289, 301 Dementia, 212, 265, 289 Denaturation, 290, 330 Dendrites, 290, 321 Density, 27, 36, 277, 290, 293, 314, 324, 343 Deoxyribonucleic, 290, 338 Deoxyribonucleic acid, 290, 338 Depolarization, 197, 290, 341 Deprivation, 211, 212, 290 Desensitization, 7, 290 Desmin, 20, 38, 55, 290 Deuterium, 290, 306 Dexrazoxane, 125, 135, 231, 290 Dextroamphetamine, 290, 317 Diabetic Foot, 219, 220, 290 Diabetic Ketoacidosis, 219, 290 Diabetic Retinopathy, 163, 164, 175, 176, 179, 187, 188, 191, 196, 199, 204, 205, 210, 220, 290 Diagnostic procedure, 159, 227, 291 Dialyzer, 291, 305 Diastole, 180, 181, 291 Diastolic blood pressure, 195, 291 Diastolic pressure, 82, 171, 291, 307 Dietary Fats, 291, 314 Digestion, 268, 275, 277, 291, 311, 314, 344 Digestive system, 156, 291 Digestive tract, 274, 291, 342 Digitalis, 291, 324 Dihydropyridines, 7, 291 Dihydrotestosterone, 291, 336 Dilatation, 3, 9, 29, 35, 61, 174, 270, 291, 332, 351, 352 Dilation, 6, 12, 25, 28, 32, 35, 45, 160, 172, 184, 185, 187, 192, 194, 207, 277, 291, 351 Dilator, 291, 323 Diltiazem, 70, 192, 291 Dilution, 291, 329 Dimethyl, 291, 312, 322 Diploid, 285, 291, 329 Dipyridamole, 76, 291 Direct, iii, 20, 22, 23, 47, 48, 52, 56, 95, 161, 169, 229, 251, 280, 281, 283, 291, 315, 336 Disinfectant, 291, 297 Dissociation, 64, 70, 267, 292, 311 Dissociative Disorders, 292
Distal, 206, 281, 292, 293, 301, 312, 327, 334 Diuretic, 196, 292, 342 Diuretics, Thiazide, 271, 292 DNA Topoisomerase, 292, 302 Dobutamine, 5, 48, 80, 105, 113, 224, 292 Dose-dependent, 8, 292, 353 Dose-limiting, 48, 292 Doxorubicin, 69, 125, 130, 135, 137, 290, 292 Drug Interactions, 230, 292 Drug Tolerance, 292, 348 Duct, 269, 279, 281, 292, 297, 339 Duodenum, 275, 292, 295, 325, 344 Dyes, 269, 275, 292, 322 Dynein, 293, 319 Dyskinesia, 179, 293 Dyslipidemia, 21, 217, 293 Dyspareunia, 293, 297 Dysplasia, 55, 74, 77, 86, 92, 214, 243, 293 Dyspnea, 150, 187, 260, 279, 289, 293 Dystrophin, 19, 27, 38, 59, 66, 69, 162, 183, 201, 293, 319 Dystrophy, 27, 29, 60, 71, 81, 191, 201, 202, 224, 226, 242, 293 E Edema, 162, 289, 290, 293, 307, 320, 331 Effector, 22, 26, 265, 284, 293, 296, 328 Efficacy, 7, 51, 71, 82, 83, 142, 155, 198, 210, 293 Ejection fraction, 71, 129, 172, 175, 185, 209, 293 Elasticity, 287, 293 Elastin, 206, 284, 293, 298 Elastomers, 186, 293 Electric shock, 289, 293 Electrocardiogram, 13, 84, 107, 141, 142, 143, 145, 150, 153, 246, 293 Electrocardiography, 208, 293 Electrode, 197, 281, 293 Electrolyte, 196, 268, 293, 313, 331, 342 Electrons, 173, 272, 275, 281, 294, 311, 316, 325, 335, 345 Electrophysiological, 161, 183, 294, 352 Elementary Particles, 294, 316, 322, 334 Emaciation, 265, 294 Embolism, 170, 294 Embolus, 294, 309 Embryo, 54, 221, 276, 281, 294, 309, 343 Embryogenesis, 62, 294 Emetic, 294, 311 Emetine, 294, 311 Enalapril, 125, 152, 294
Index 361
Encephalitis, 40, 294 Encephalitis, Viral, 294 Endemic, 57, 294, 343 Endocarditis, 218, 294 Endocardium, 207, 294, 295 Endocytosis, 69, 281, 295 Endometrial, 173, 295 Endometrium, 289, 295 Endoscope, 295 Endoscopic, 178, 295 Endothelial cell, 8, 33, 92, 170, 295, 299, 300, 347 Endothelium, 33, 295, 322, 329 Endothelium, Lymphatic, 295 Endothelium, Vascular, 295 Endothelium-derived, 295, 322 Endotoxic, 295, 314 Endotoxin, 295, 350 End-stage renal, 3, 213, 218, 283, 295, 330 Energetic, 14, 21, 66, 295 Energy balance, 295, 313 Enhancer, 54, 62, 295, 337 Enoximone, 190, 295 Environmental Exposure, 295, 323 Environmental Health, 236, 238, 295 Environmental Pollutants, 54, 296 Enzymatic, 39, 49, 57, 278, 280, 285, 296, 299, 306, 313, 330, 337 Enzyme, 14, 22, 54, 163, 164, 176, 184, 188, 196, 199, 205, 266, 267, 268, 269, 280, 284, 288, 292, 293, 294, 296, 300, 303, 304, 312, 314, 317, 320, 328, 329, 330, 333, 334, 336, 337, 338, 341, 345, 347, 348, 349, 350, 352, 353 Enzyme Induction, 296, 337 Enzyme Repression, 296, 337 Eosinophils, 296, 303, 313 Epidemic, 63, 296, 343 Epidemiological, 213, 218, 296 Epidermis, 296, 307 Epidural, 82, 296 Epidural block, 82, 296 Epigastric, 296, 325 Epinephrine, 196, 266, 296, 323, 350 Epithelial, 289, 296, 305, 313 Epithelial Cells, 296, 305, 313 Epithelium, 275, 295, 296, 300 Ergometer, 151, 296 Erythrocytes, 270, 277, 279, 296 Esophageal, 296, 301 Esophagitis, 296, 301
Esophagus, 291, 296, 301, 315, 328, 336, 344 Essential Tremor, 242, 296 Estrogen, 6, 172, 173, 297 Estrogen Replacement Therapy, 173, 297 Ethanol, 7, 23, 109, 207, 297 Eukaryotic Cells, 289, 297, 309, 324, 350 Evoke, 297, 344 Excitability, 14, 297 Excitation, 7, 15, 23, 31, 46, 140, 273, 282, 297, 298 Excitatory, 274, 297, 308 Excrete, 272, 297, 312 Exercise Test, 143, 145, 147, 149, 151, 155, 226, 297 Exocrine, 297, 325 Exogenous, 297, 301, 350 Exon, 42, 162, 183, 268, 297 Expiration, 297, 337 Extracellular, 14, 62, 162, 183, 197, 202, 218, 219, 269, 273, 286, 295, 297, 298, 299, 316, 342 Extracellular Matrix, 62, 162, 183, 197, 202, 286, 297, 299, 316 Extracellular Matrix Proteins, 297, 316 Extracellular Space, 297, 298 Extraction, 44, 298 Extravascular, 175, 209, 298 Extremity, 277, 298, 316 Eye Infections, 266, 298 F Facial, 268, 298, 342 Facial Paralysis, 268, 298 Family Planning, 237, 298 Fat, 6, 21, 44, 65, 70, 266, 272, 277, 278, 280, 287, 294, 298, 312, 313, 314, 324, 338, 342, 349 Fatigue, 60, 77, 143, 147, 150, 152, 153, 200, 211, 260, 298, 304 Fatty acids, 18, 21, 47, 130, 267, 290, 298, 303, 332, 347 Felodipine, 192, 298 Femoral, 146, 204, 298 Femoral Artery, 146, 298 Femur, 298 Fendiline, 192, 298 Ferritin, 32, 298 Fetus, 97, 221, 298, 329, 331, 343, 351 Fibril, 51, 220, 298 Fibrillation, 289, 298, 341 Fibrin, 276, 284, 298, 299, 329, 347, 348 Fibrinogen, 82, 298, 329, 347
362
Cardiomyopathy
Fibrinolysis, 196, 299 Fibrinolytic, 9, 299 Fibroblast Growth Factor, 10, 170, 299 Fibroblasts, 23, 40, 55, 166, 208, 286, 299, 310 Fibrosis, 9, 22, 54, 55, 68, 114, 153, 171, 174, 191, 194, 195, 243, 299, 339 Fibula, 299, 330 Fistula, 299, 323 Flatus, 299, 300 Flunarizine, 192, 299 Fluorescence, 10, 18, 33, 64, 299 Fluorouracil, 291, 299 Fold, 8, 299 Foot Ulcer, 164, 187, 199, 210, 290, 299 Foramen, 68, 299, 327 Forearm, 277, 299, 316 Forskolin, 15, 299 Friction, 186, 299 Fructose, 164, 175, 176, 199, 205, 299, 303 Fungi, 57, 298, 300, 318, 353 Fura-2, 43, 300 G GABA, 163, 164, 176, 187, 199, 274, 300, 319, 341 GABA Agonists, 163, 300 Gadolinium, 5, 87, 114, 300 Gait, 177, 282, 300 Gait Ataxia, 177, 282, 300 Galactitol, 163, 176, 188, 205, 300 Galactokinase, 300 Galactosemia, 300 Gallbladder, 265, 291, 300 Gallopamil, 192, 300 Ganglia, 265, 275, 300, 321, 327, 345 Ganglionic Blockers, 271, 300 Gas, 71, 279, 289, 299, 300, 306, 322, 323, 351 Gas exchange, 300, 351 Gastric, 188, 280, 300, 301, 306, 311 Gastric Mucosa, 300, 311 Gastrin, 301, 306 Gastroesophageal Reflux, 211, 212, 301 Gastroesophageal Reflux Disease, 211, 212, 301 Gastrointestinal, 57, 212, 272, 277, 296, 297, 301, 314, 341, 342, 344, 350 Gastrointestinal tract, 57, 212, 272, 297, 301, 314, 341, 342, 344, 350 Gelatin, 301, 303, 347 Gene Deletion, 162, 183, 301 Gene Targeting, 62, 301
Generator, 165, 301 Genetic Code, 301, 323 Genetic Engineering, 38, 276, 284, 301 Genetic Markers, 30, 96, 301 Genetic Screening, 116, 301 Genetic testing, 301, 330 Genetics, 29, 39, 50, 77, 85, 87, 90, 94, 97, 102, 123, 149, 219, 302 Genistein, 6, 302 Genital, 274, 302 Genomics, 15, 30, 65, 203, 302 Genotype, 32, 38, 67, 74, 302, 328 Germ Cells, 53, 302, 316, 324, 342 Gestation, 302, 329, 331, 343 Gestational, 219, 302 Gland, 266, 287, 302, 325, 329, 333, 340, 344, 347 Glomerular, 191, 196, 204, 302, 312, 322, 336 Glomerular Filtration Rate, 302, 312, 322 Glomeruli, 302 Glomerulonephritis, 191, 196, 302 Glomerulus, 302, 312 Glucocorticoid, 302, 331 Glucose, 6, 21, 22, 26, 32, 33, 35, 47, 51, 96, 122, 163, 164, 167, 176, 179, 188, 205, 219, 220, 242, 267, 271, 273, 276, 290, 300, 302, 303, 305, 310, 328, 342 Glucose Intolerance, 290, 302 Glucose tolerance, 51, 179, 219, 302 Glucose Tolerance Test, 219, 302, 303 Glutathione Peroxidase, 303, 340 Glycerol, 278, 303, 328 Glycerophospholipids, 303, 328 Glycine, 303, 340 Glycogen, 66, 114, 176, 195, 199, 205, 303, 328 Glycogen Storage Disease, 66, 303 Glycolysis, 14, 15, 303 Glycoprotein, 19, 27, 66, 162, 183, 201, 298, 303, 313, 347, 350 Glycoside, 303, 324 Glycosidic, 303, 328 Glycosylation, 32, 170, 303 Gonads, 303, 307 Governing Board, 303, 331 Grade, 27, 303 Graft, 303, 306, 309, 320 Grafting, 15, 303, 309 Granulocytes, 303, 341, 352 Gravis, 212, 303 Groin, 154, 304
Index 363
Growth factors, 169, 304 Guanylate Cyclase, 304, 322 H Habitual, 282, 304 Haptens, 267, 304 Headache, 304, 309 Health Status, 304, 353 Heart attack, 25, 155, 280, 304 Heart Catheterization, 154, 304 Heart Transplantation, 47, 68, 101, 111, 304 Heart Valves, 197, 304 Heart Ventricle, 171, 178, 283, 304 Heartbeat, 154, 197, 260, 304, 345, 351 Helix-loop-helix, 54, 304 Heme, 275, 288, 304 Hemiplegia, 268, 304 Hemochromatosis, 13, 31, 305 Hemodialysis, 3, 217, 291, 305, 312, 313 Hemoglobin, 219, 270, 296, 304, 305, 312, 347 Hemoglobinuria, 242, 305 Hemolytic, 305, 346 Hemorrhage, 304, 305, 320, 344, 352 Hemostasis, 305, 341 Heparan Sulfate Proteoglycan, 220, 305 Hepatic, 21, 241, 267, 294, 302, 305 Hepatitis, 104, 120, 169, 305 Hepatocytes, 305 Hepatomegaly, 115, 305 Hereditary, 13, 31, 69, 122, 305, 338, 346 Heredity, 301, 302, 305 Heterodimer, 193, 305 Heterogeneity, 27, 30, 56, 86, 267, 305 Heterogenic, 305 Heterogenous, 219, 305 Heterotrophic, 300, 305 Heterozygote, 62, 305 Histamine, 270, 299, 306 Histology, 42, 56, 306 Homeostasis, 8, 12, 14, 16, 21, 26, 32, 46, 54, 177, 306, 342 Homodimer, 174, 306 Homogeneous, 94, 286, 306 Homologous, 202, 268, 276, 301, 305, 306, 346 Hormonal, 110, 196, 219, 274, 297, 306, 327 Hormone therapy, 122, 306 Host, 48, 50, 274, 298, 306, 308, 309, 314, 352 Human growth hormone, 122, 306, 342 Hybrid, 191, 306
Hybridization, 54, 56, 306 Hybridomas, 306, 310 Hydrogen Peroxide, 303, 306, 314, 345 Hydrolysis, 34, 306, 313, 328, 330, 334 Hydrophilic, 186, 306 Hydrophobic, 203, 303, 306, 314 Hydrops Fetalis, 97, 307 Hydroxylysine, 284, 307 Hydroxyproline, 284, 307 Hyperaldosteronism, 191, 307 Hyperbilirubinemia, 221, 307, 312 Hypercholesterolemia, 205, 293, 307 Hyperglycemia, 21, 22, 32, 167, 179, 195, 205, 307 Hyperhomocysteinemia, 217, 288, 307 Hyperlipidemia, 34, 205, 214, 217, 293, 307 Hyperpigmentation, 54, 307 Hyperplasia, 45, 191, 196, 307 Hypersensitivity, 182, 268, 290, 307, 314, 338 Hyperthyroidism, 109, 307 Hypertriglyceridemia, 293, 307 Hypoglycemia, 206, 221, 307 Hypoglycemic, 180, 205, 307 Hypoglycemic Agents, 180, 205, 307 Hypogonadism, 240, 241, 307 Hypotension, 4, 218, 300, 307 Hypothalamus, 274, 277, 307, 329, 342 Hypoxanthine, 308, 353 Hypoxia, 211, 212, 308, 346 I Ibotenic Acid, 308, 319 Id, 97, 126, 135, 240, 241, 242, 246, 249, 256, 258, 308 Idarubicin, 125, 308 Iliac Artery, 298, 308 Imaging procedures, 308, 348 Immune function, 203, 308 Immune response, 266, 270, 271, 274, 287, 304, 308, 344, 352 Immune Sera, 308 Immune system, 274, 276, 308, 309, 314, 315, 351, 352 Immunity, 50, 171, 203, 265, 267, 308, 349 Immunization, 50, 308, 309 Immunodeficiency, 66, 81, 242, 265, 308 Immunofluorescence, 14, 202, 308 Immunogenic, 308, 314 Immunoglobulin, 209, 271, 308, 319 Immunohistochemistry, 50, 56, 308 Immunologic, 29, 182, 282, 308, 326, 353 Immunology, 133, 203, 266, 267, 308
364
Cardiomyopathy
Immunophilin, 278, 308 Immunosuppressive, 226, 278, 302, 308, 309 Immunotherapy, 276, 290, 309 Impairment, 33, 38, 44, 74, 86, 172, 184, 204, 211, 212, 273, 293, 298, 300, 309, 317 Implantation, 145, 178, 285, 309 In situ, 22, 50, 56, 309 In Situ Hybridization, 57, 309 In vitro, 8, 14, 15, 16, 20, 24, 32, 36, 39, 40, 42, 43, 48, 51, 54, 57, 61, 64, 161, 309, 330, 348 Incision, 309, 311 Incompetence, 301, 309 Indicative, 52, 214, 309, 326, 351 Induction, 7, 31, 32, 121, 132, 166, 167, 300, 309 Infancy, 309, 338 Infantile, 241, 309, 314 Infarction, 5, 9, 15, 17, 18, 28, 31, 45, 72, 86, 88, 98, 124, 162, 163, 166, 185, 188, 191, 195, 196, 204, 207, 287, 292, 309, 317, 320, 337, 352 Inferior vena cava, 181, 309 Infiltration, 302, 309, 332 Influenza, 169, 309 Infusion, 48, 96, 122, 309, 320, 349 Ingestion, 7, 133, 302, 310, 330 Inhalation, 310, 330 Initiation, 6, 11, 44, 45, 51, 59, 140, 310, 332, 348 Inlay, 310, 337 Innervation, 76, 106, 131, 277, 310, 316 Inorganic, 52, 310, 328 Inositol, 310, 340 Inotropic, 23, 48, 190, 269, 295, 298, 310, 318 Insight, 17, 21, 27, 32, 33, 38, 40, 49, 53, 55, 60, 61, 181, 310 Instillation, 178, 310 Insulin-dependent diabetes mellitus, 210, 310 Insulin-like, 6, 32, 44, 149, 310 Interferon, 83, 120, 132, 166, 310 Interferon-alpha, 166, 310 Interferon-beta, 166, 310 Interleukin-6, 83, 310 Intermittent, 310, 327 Interstitial, 22, 62, 162, 174, 195, 298, 310, 336 Intestinal, 280, 302, 310, 316 Intestine, 277, 284, 310, 313
Intoxication, 7, 311, 353 Intramuscular, 161, 311 Intramuscular injection, 161, 311 Intraocular, 299, 311 Intraocular pressure, 299, 311 Intravascular, 175, 209, 304, 311 Intravenous, 143, 219, 310, 311, 335 Intrinsic, 14, 29, 33, 37, 43, 44, 165, 197, 267, 275, 311 Introns, 166, 311 Intubation, 281, 311 Invasive, 4, 13, 48, 52, 56, 113, 168, 178, 208, 308, 311, 316 Involuntary, 275, 296, 298, 311, 320, 336, 343 Iodine, 106, 311 Ion Channels, 13, 188, 273, 311 Ion Exchange, 199, 311 Ionization, 10, 311 Ions, 164, 275, 278, 279, 292, 293, 306, 311, 339 Ipecac, 130, 132, 133, 294, 311 Islet, 180, 219, 312 Isoenzyme, 288, 312 Isoleucine, 51, 312 Isradipine, 192, 312 J Jaundice, 307, 312 Joint, 273, 289, 312, 346 K Kallidin, 277, 312 Kb, 236, 312 Ketone Bodies, 290, 312 Ketosis, 290, 312 Kidney Cortex, 312, 317 Kidney Disease, 156, 220, 236, 243, 312 Kidney Failure, 218, 295, 312 Kidney Failure, Acute, 312 Kidney Failure, Chronic, 312 Kinesin, 313, 319 Kinetic, 34, 39, 313 L Labile, 284, 313 Laminin, 202, 275, 298, 313 Large Intestine, 284, 291, 311, 313, 336, 342 Latent, 22, 67, 171, 313, 331 Laxative, 267, 313, 342 Leishmania, 57, 313 Leishmaniasis, 57, 313, 326 Lens, 20, 163, 176, 188, 205, 280, 288, 300, 313, 352 Leprosy, 299, 313
Index 365
Leptin, 21, 313 Lesion, 185, 206, 268, 299, 313, 315, 339 Lethal, 34, 66, 67, 171, 226, 242, 274, 313 Leukemia, 242, 283, 292, 313 Leukocytes, 42, 193, 275, 277, 282, 296, 303, 310, 313, 314, 322, 350 Leukopenia, 314, 353 Leukotrienes, 272, 314 Levo, 314, 317 Library Services, 256, 314 Life cycle, 276, 300, 313, 314 Ligament, 314, 333 Ligands, 212, 314, 345 Ligation, 60, 314 Linkage, 22, 27, 29, 38, 59, 96, 144, 150, 190, 301, 314 Lipase, 68, 96, 314 Lipid A, 19, 37, 140, 173, 206, 314 Lipid Peroxidation, 16, 314, 325 Lipodystrophy, 98, 314 Lipopolysaccharides, 314, 338 Lipoprotein, 68, 96, 293, 314, 315 Liposomes, 170, 314 Liver, 21, 51, 168, 180, 182, 212, 265, 267, 269, 272, 275, 279, 280, 288, 291, 300, 302, 303, 305, 314, 315, 317, 331, 335, 337, 339, 350 Liver scan, 315, 339 Liver Transplantation, 51, 315 Lobe, 306, 315 Lobectomy, 103, 315 Localization, 308, 315 Longitudinal study, 21, 315 Loop, 11, 109, 315 Low-density lipoprotein, 293, 314, 315 Lower Esophageal Sphincter, 301, 315 Lucida, 313, 315 Lumen, 186, 206, 279, 295, 315 Lupus, 284, 315 Lymph, 282, 283, 295, 315, 339 Lymphatic, 137, 295, 309, 315, 317, 342, 343, 347 Lymphocyte, 265, 271, 315, 316 Lymphocyte Count, 265, 315 Lymphoid, 271, 287, 315 Lymphoma, 242, 315 Lytic, 315, 341 M Magnetic Resonance Imaging, 68, 87, 98, 145, 147, 155, 316, 339 Magnetic Resonance Spectroscopy, 105, 316
Malabsorption, 242, 316 Malformation, 122, 316 Malignant, 87, 242, 265, 272, 316, 321 Malnutrition, 4, 267, 274, 279, 316, 319 Mammogram, 278, 316, 318 Manifest, 26, 51, 162, 304, 316 Matrix metalloproteinase, 62, 316 Median Nerve, 212, 280, 316 Mediate, 11, 34, 39, 42, 45, 62, 316 Mediator, 37, 42, 166, 196, 316, 341 Medical Records, 316, 338 MEDLINE, 237, 239, 243, 316 Meiosis, 276, 316, 346 Melanin, 316, 328, 350 Melanocytes, 307, 316 Melanoma, 242, 316 Melphalan, 220, 317 Membrane Fluidity, 26, 317 Membrane Proteins, 281, 314, 317, 343 Memory, 290, 317 Meninges, 282, 317, 343 Menopause, 173, 317, 331 Menstruation, 268, 289, 317, 323 Mental Disorders, 157, 317, 334 Mental Health, iv, 4, 157, 236, 238, 317, 334 Mental Processes, 292, 317, 334 Mesenchymal, 67, 317 Metabolic disorder, 48, 303, 317 Metabolite, 22, 291, 296, 317, 332 Metallothionein, 49, 317 Metastasis, 316, 317, 321 Methamphetamine, 79, 317 Methionine, 51, 291, 317, 345 Metoprolol, 83, 133, 317 MI, 5, 15, 17, 151, 205, 207, 262, 317 Mibefradil, 192, 318 Microbe, 318, 348 Microbiological, 99, 318 Microbiology, 133, 266, 318 Microcalcifications, 278, 318 Microcirculation, 196, 318, 329 Microfilaments, 40, 318 Microorganism, 284, 318, 352 Microscopy, 20, 21, 23, 49, 96, 275, 318 Microtubules, 313, 318, 325 Migration, 37, 39, 197, 318 Milrinone, 190, 318 Mitochondria, 34, 65, 124, 177, 318, 320, 324 Mitochondrial Swelling, 318, 321 Mitosis, 272, 318
366
Cardiomyopathy
Mitotic, 28, 318 Mitral Valve, 72, 78, 92, 95, 97, 175, 189, 194, 197, 318 Mobility, 14, 318 Modeling, 12, 24, 318 Modification, 18, 36, 67, 178, 301, 318, 335, 353 Molecular Motors, 39, 318 Molecule, 13, 24, 32, 34, 39, 51, 181, 271, 275, 279, 284, 285, 288, 292, 293, 295, 297, 303, 306, 319, 323, 325, 328, 330, 336, 341, 348, 351 Monitor, 86, 117, 143, 147, 149, 154, 178, 208, 288, 319, 323 Monoclonal, 219, 306, 319, 335 Monocyte, 37, 123, 319 Mononuclear, 319, 350 Morphogenesis, 62, 319 Morphological, 12, 69, 294, 316, 319 Morphology, 12, 105, 107, 280, 319 Motility, 39, 61, 319, 341 Motor nerve, 220, 319, 327 Mucocutaneous, 313, 319 Multivariate Analysis, 151, 319 Muscimol, 164, 319 Muscle Contraction, 34, 60, 63, 270, 293, 319, 339 Muscle Fibers, 194, 273, 319, 320, 341, 349 Muscle Proteins, 286, 319 Muscle relaxant, 201, 299, 319 Muscle tension, 319 Muscular Atrophy, 242, 319 Muscular Dystrophies, 19, 76, 202, 293, 319 Mutagenesis, 38, 320 Mutagenic, 53, 320 Mutagens, 320 Myalgia, 309, 320 Myasthenia, 212, 320 Mydriatic, 291, 320 Myocardial Ischemia, 4, 5, 107, 146, 147, 152, 154, 169, 196, 205, 270, 287, 320 Myocardial Reperfusion, 320, 337 Myocardial Reperfusion Injury, 320, 337 Myocarditis, 16, 19, 40, 41, 59, 99, 117, 132, 169, 182, 183, 204, 210, 214, 215, 216, 247, 320 Myofibrils, 192, 194, 279, 293, 320 Myopathy, 20, 27, 36, 59, 99, 123, 131, 132, 173, 175, 196, 209, 215, 240, 241, 246, 320 Myotonic Dystrophy, 42, 242, 320
N Nasal Mucosa, 309, 321 Natriuresis, 196, 270, 321 Natural selection, 276, 321 Nausea, 312, 321, 350 NCI, 1, 156, 235, 283, 321 Necrosis, 32, 40, 49, 115, 272, 309, 317, 320, 321, 337, 338, 339, 340 Neonatal, 13, 14, 321 Neoplasia, 198, 242, 321 Neoplasms, 265, 272, 289, 321, 346 Neoplastic, 306, 315, 321 Nephrologist, 217, 321 Nervous System, 7, 139, 164, 188, 196, 212, 220, 242, 265, 267, 274, 275, 277, 278, 282, 290, 300, 304, 314, 316, 317, 321, 324, 326, 327, 330, 341, 345 Neural, 124, 267, 269, 300, 321, 327 Neurogenic, 16, 321 Neurologic, 52, 212, 321 Neuronal, 278, 321, 327 Neurons, 60, 163, 164, 188, 290, 297, 300, 319, 321, 345, 346 Neuropeptides, 16, 279, 321 Neurophysiology, 290, 321 Neutrons, 268, 322, 335 Neutrophils, 300, 303, 313, 322 Niacin, 322, 349 Niacinamide, 322 Nicardipine, 192, 322 Nicorandil, 82, 201, 322 Nifedipine, 7, 192, 322 Nimodipine, 192, 322 Nisoldipine, 192, 322 Nitrendipine, 192, 322 Nitric Oxide, 16, 23, 33, 42, 47, 82, 166, 322 Nitrogen, 76, 268, 289, 297, 312, 317, 322, 349 Nitroglycerin, 71, 323 Norepinephrine, 58, 151, 196, 266, 323 Nuclei, 194, 268, 294, 298, 301, 311, 316, 318, 322, 323, 324, 334 Nucleic acid, 169, 181, 301, 306, 308, 309, 320, 323, 335, 338, 353 Nucleic Acid Hybridization, 306, 323 Nutritional Status, 144, 323 O Observational study, 116, 323 Octreotide, 93, 212, 323 Ocular, 162, 323 Oligomenorrhea, 323, 330 Oliguria, 312, 323
Index 367
Oncogene, 6, 242, 323 Opacity, 20, 280, 290, 324 Operon, 324, 332, 337 Opportunistic Infections, 265, 324 Opsin, 324, 337 Optic Disk, 287, 291, 324 Optic Nerve, 324, 337 Organ Culture, 324, 348 Organelles, 289, 313, 316, 324 Orthostatic, 58, 323, 324 Ossification, 324, 338 Osteomyelitis, 220, 324 Osteoporosis, 297, 324 Ouabain, 54, 324 Outpatient, 142, 324 Ovaries, 324, 330, 341 Ovary, 179, 303, 324 Overexpress, 16, 63, 324 Overweight, 126, 144, 324 Oxidation, 6, 14, 22, 33, 34, 37, 44, 70, 124, 199, 265, 272, 288, 290, 303, 314, 325 Oxidative Phosphorylation, 48, 173, 325 Oxidative Stress, 16, 21, 25, 47, 49, 64, 100, 106, 130, 325 Oxygen Consumption, 44, 47, 151, 295, 297, 325, 337 Oxygenation, 178, 289, 325 P Pacemaker, 30, 144, 145, 155, 165, 172, 180, 186, 223, 325 Paclitaxel, 135, 325 Palliative, 325, 347 Palsy, 268, 325 Pancreas, 168, 180, 219, 265, 276, 291, 305, 310, 312, 314, 325, 342, 350 Pancreatic, 21, 63, 180, 210, 242, 280, 301, 325 Pancreatic cancer, 242, 325 Pancreatic Juice, 301, 325 Papilla, 325 Papillary, 11, 24, 38, 283, 325 Papillary Muscles, 24, 283, 325 Paralysis, 267, 288, 298, 325 Parasite, 40, 50, 57, 325 Parasitic, 57, 275, 325 Parathyroid, 325, 326, 338 Parathyroid Glands, 325, 326, 338 Paroxysmal, 79, 242, 270, 326 Particle, 326, 342, 348 Parturition, 47, 326 Patch, 7, 83, 287, 326
Pathologic, 7, 44, 59, 62, 64, 87, 130, 166, 203, 265, 272, 276, 277, 287, 307, 326, 343, 351 Pathologic Processes, 59, 272, 326 Pathologies, 21, 168, 326 Pathophysiology, 13, 25, 26, 27, 43, 46, 47, 51, 54, 61, 63, 101, 121, 140, 196, 219, 326 Patient Satisfaction, 142, 326 Pedigree, 171, 326 Pelvic, 326, 333 Pentamidine, 16, 326 Pentoxifylline, 124, 326 Peptide, 17, 20, 23, 44, 49, 76, 117, 166, 197, 203, 211, 299, 313, 326, 330, 333, 334, 345 Percutaneous, 80, 98, 102, 111, 118, 145, 146, 175, 209, 326 Perforation, 155, 299, 326 Perfusion, 22, 42, 86, 94, 99, 100, 110, 118, 124, 155, 187, 207, 211, 214, 217, 308, 326 Pericarditis, 217, 218, 326 Pericardium, 326 Periodicity, 326, 338 Peripheral blood, 207, 310, 327 Peripheral Nerves, 212, 313, 327, 343 Peripheral Nervous System, 204, 300, 304, 325, 327, 342, 344 Peripheral Nervous System Diseases, 300, 304, 327 Peripheral Neuropathy, 51, 327 Peripheral Vascular Disease, 196, 219, 220, 299, 327 Peritoneal, 217, 327 Peritoneal Cavity, 327 Peritoneal Dialysis, 217, 327 Peritoneum, 327 Perivascular, 162, 327 PH, 66, 120, 327 Pharmacologic, 5, 95, 270, 327, 348 Pharmacotherapy, 49, 131, 132, 134, 327 Pharynx, 301, 309, 327 Phenylalanine, 328, 350 Phosphates, 6, 328 Phosphodiesterase, 176, 179, 190, 199, 269, 295, 318, 326, 328 Phospholipase C, 26, 328 Phospholipases, 18, 26, 37, 328, 341 Phospholipids, 18, 298, 310, 314, 317, 328 Phosphorus, 278, 326, 328 Phosphorylase, 176, 195, 199, 205, 279, 328 Phosphorylate, 173, 328 Phosphorylated, 10, 174, 284, 328 Phosphorylating, 32, 328
368
Cardiomyopathy
Phosphorylation, 10, 11, 14, 32, 36, 38, 43, 44, 139, 328, 333 Phototransduction, 328, 340 Physical Examination, 142, 143, 150, 153, 328 Physiologic, 22, 29, 37, 42, 165, 267, 276, 317, 328, 332, 336, 346 Physiology, 7, 17, 19, 30, 34, 36, 44, 46, 47, 55, 192, 279, 294, 321, 328 Pigment, 275, 316, 328 Pigmentation, 307, 328 Pilot study, 116, 329 Pituitary Gland, 197, 299, 329 Placenta, 47, 329 Plants, 268, 275, 276, 278, 279, 283, 291, 300, 302, 303, 319, 323, 324, 329, 339, 348, 350 Plaque, 194, 204, 206, 329 Plasma cells, 271, 329 Plasma Volume, 218, 277, 329 Plasmin, 8, 329, 348, 350 Plasminogen, 8, 329, 348, 350 Plasminogen Activators, 329 Plasticity, 193, 329 Platelet Activation, 329, 341 Platelet Aggregation, 270, 299, 322, 326, 329, 347 Platelets, 180, 188, 279, 322, 329, 347 Platinum, 186, 315, 329 Point Mutation, 11, 16, 24, 34, 60, 191, 330 Poisoning, 169, 282, 311, 321, 330 Polycystic, 179, 243, 330 Polycystic Ovary Syndrome, 179, 330 Polyhydramnios, 221, 330 Polymerase, 108, 330, 332, 337, 338 Polymerase Chain Reaction, 108, 330 Polymers, 330, 333, 344 Polymorphic, 27, 29, 108, 330 Polymorphism, 30, 88, 115, 330 Polypeptide, 268, 284, 299, 306, 329, 330, 333, 342, 347, 349, 353 Polyposis, 284, 330 Polysaccharide, 271, 330, 334 Pons, 268, 298, 330 Popliteal, 204, 330 Porosity, 185, 330 Port, 78, 80, 85, 206, 330 Port-a-cath, 330 Post partum, 47, 331 Posterior, 269, 273, 283, 325, 331 Postmenopausal, 297, 324, 331 Postnatal, 331, 344
Postsynaptic, 331, 341 Postural, 58, 331 Potassium, 12, 13, 96, 122, 268, 292, 322, 331 Potentiate, 32, 331 Potentiation, 331, 341 Practice Guidelines, 72, 238, 331 Precipitating Factors, 281, 331 Precipitation, 28, 331 Preclinical, 71, 103, 331 Precursor, 164, 196, 216, 219, 270, 272, 283, 293, 296, 323, 328, 329, 331, 332, 349, 350 Predisposition, 185, 220, 331 Prednisolone, 331 Prednisone, 220, 331 Pre-Eclampsia, 47, 331 Prenatal, 294, 301, 331 Presynaptic, 164, 188, 331 Prevalence, 3, 12, 38, 51, 78, 104, 116, 146, 174, 210, 219, 331 Probe, 18, 34, 143, 154, 203, 332 Procaine, 267, 332 Prodrug, 163, 164, 187, 188, 199, 332 Prognostic factor, 149, 225, 332 Projection, 323, 324, 332, 336 Proliferative Retinopathy, 220, 332 Proline, 284, 307, 332 Promoter, 17, 38, 40, 46, 54, 55, 62, 162, 183, 332 Promotor, 332, 337 Prophase, 276, 332, 346 Prophylaxis, 109, 299, 332 Proportional, 332, 345 Prospective Studies, 25, 332 Prospective study, 123, 315, 332 Prostaglandin, 184, 270, 332, 347 Prostaglandins A, 332, 333 Prostaglandins B, 184, 333 Prostaglandins F, 333 Prostate, 242, 276, 333, 350 Prosthesis, 84, 333 Protease, 59, 121, 284, 333, 348 Protein C, 42, 62, 173, 198, 219, 265, 267, 269, 274, 298, 314, 319, 333, 343, 349, 350 Protein Conformation, 219, 269, 333 Protein Isoforms, 8, 268, 333 Protein S, 9, 23, 26, 37, 44, 59, 193, 203, 243, 276, 294, 301, 306, 333, 338, 346 Proteins, 8, 9, 10, 12, 16, 17, 18, 20, 21, 24, 25, 26, 27, 28, 31, 32, 36, 37, 39, 40, 43, 45, 50, 51, 54, 55, 56, 58, 60, 61, 63, 113, 161, 170, 177, 193, 198, 200, 201, 203,
Index 369
219, 268, 269, 271, 277, 279, 280, 281, 283, 284, 286, 288, 293, 295, 297, 303, 305, 306, 312, 316, 317, 319, 320, 323, 326, 329, 330, 333, 334, 336, 337, 338, 341, 345, 347, 348 Protein-Tyrosine Kinase, 302, 333 Proteinuria, 191, 196, 220, 331, 334 Proteoglycans, 206, 275, 298, 334 Proteolytic, 51, 219, 268, 285, 299, 329, 334, 348, 350 Protocol, 74, 147, 334 Protons, 268, 306, 316, 334, 335 Proto-Oncogene Proteins, 325, 334 Proto-Oncogene Proteins c-mos, 325, 334 Protozoa, 57, 313, 318, 334, 349 Proximal, 27, 206, 292, 312, 331, 334, 340 Proxy, 130, 334 Psychiatric, 124, 317, 334 Psychiatry, 74, 132, 334 Psychology, 292, 334 Public Health, 150, 238, 334 Public Policy, 237, 334 Publishing, 3, 65, 334 Pulmonary, 66, 71, 109, 143, 169, 175, 181, 187, 190, 191, 195, 196, 209, 210, 211, 269, 276, 286, 297, 304, 312, 314, 334, 335, 351 Pulmonary Artery, 181, 276, 334, 351 Pulmonary congestion, 195, 334 Pulmonary Edema, 196, 312, 334 Pulmonary hypertension, 66, 109, 190, 191, 196, 335 Pulse, 17, 79, 164, 165, 319, 335 Pupil, 291, 320, 335 Purines, 335, 340, 353 Pyogenic, 324, 335 Q Quality of Life, 4, 52, 77, 96, 142, 145, 148, 150, 335 Quaternary, 333, 335 R Race, 107, 217, 317, 318, 335 Radiation, 155, 207, 265, 270, 287, 294, 295, 299, 335, 339, 353 Radiation therapy, 265, 335 Radioactive, 147, 154, 277, 306, 309, 311, 315, 323, 335, 339 Radioisotope, 335, 348 Radioisotope Renography, 335 Radiological, 326, 335 Radionuclide Angiography, 56, 145, 147, 335
Radiopharmaceutical, 301, 335 Randomized, 17, 72, 142, 148, 151, 153, 293, 335 Randomized clinical trial, 17, 335 Reactivation, 14, 40, 336 Reactive Oxygen Species, 25, 32, 33, 48, 49, 66, 336 Receptors, Serotonin, 336, 341 Recombinant, 20, 43, 51, 75, 122, 161, 169, 181, 336, 351 Recombination, 301, 336 Rectum, 272, 277, 284, 291, 299, 300, 313, 333, 336 Red Nucleus, 273, 336 Reductase, 57, 162, 163, 164, 175, 176, 188, 199, 205, 267, 336 Refer, 1, 284, 300, 315, 322, 330, 336, 340 Reflective, 50, 336 Reflex, 60, 336 Reflux, 211, 212, 301, 336 Refraction, 336, 343 Refractory, 13, 81, 101, 165, 336 Regeneration, 111, 207, 299, 336 Regimen, 48, 81, 293, 327, 336 Regurgitation, 15, 25, 88, 166, 175, 189, 197, 209, 301, 304, 336 Relaxant, 336 Renal failure, 191, 196, 220, 305, 336 Renin, 32, 46, 55, 61, 196, 270, 336, 337 Renin-Angiotensin System, 32, 270, 337 Reperfusion, 16, 31, 43, 210, 320, 337 Reperfusion Injury, 31, 210, 337 Repressor, 63, 324, 337 Repressor Proteins, 63, 337 Reproductive cells, 302, 337 Respiration, 181, 272, 279, 282, 288, 319, 337 Response Elements, 54, 337 Restoration, 54, 95, 161, 183, 320, 336, 337, 353 Restrictive cardiomyopathy, 68, 70, 86, 100, 107, 108, 134, 187, 216, 226, 337 Retina, 20, 176, 199, 205, 283, 286, 287, 290, 313, 324, 328, 332, 337, 338, 339, 352 Retinal, 21, 204, 291, 324, 328, 337 Retinoblastoma, 242, 338 Retinol, 337, 338 Retinopathy, 163, 164, 179, 188, 210, 219, 220, 221, 267, 290, 338 Retrograde, 124, 338 Retrospective, 88, 338 Retrospective study, 88, 338
370
Cardiomyopathy
Reverse Transcriptase Inhibitors, 48, 338 Reversion, 102, 280, 338 Rhabdomyolysis, 70, 338 Rhamnose, 324, 338 Rheology, 326, 338 Rheumatism, 338 Rheumatoid, 220, 284, 338 Rheumatoid arthritis, 220, 284, 338 Rhythmicity, 7, 338 Ribonucleic acid, 71, 338 Ribose, 266, 338 Ribosome, 338, 349 Rickets, 71, 91, 338 Risk factor, 4, 6, 22, 43, 52, 149, 173, 217, 281, 307, 332, 339 Rod, 283, 339 Rosiglitazone, 180, 339 Rubber, 293, 339 S Salivary, 288, 291, 325, 339 Salivary glands, 288, 291, 339 Saponin, 23, 339 Sarcoid, 187, 339 Sarcoidosis, 339 Sarcolemma, 200, 201, 320, 339 Sarcomere, 24, 174, 192, 193, 226, 339 Sarcoplasmic Reticulum, 12, 23, 27, 36, 339 Scans, 29, 145, 154, 339 Schizoid, 339, 353 Schizophrenia, 339, 353 Schizotypal Personality Disorder, 339, 353 Scleroderma, 191, 196, 339 Sclerosis, 191, 196, 212, 242, 284, 339 Second Messenger Systems, 7, 340 Secretion, 8, 32, 63, 161, 180, 306, 310, 323, 340 Segmental, 5, 78, 94, 115, 340 Segmentation, 340 Seizures, 326, 340 Selenium, 121, 123, 124, 125, 127, 133, 135, 340 Sella, 329, 340 Semen, 333, 340 Senile, 51, 324, 340 Sensor, 165, 180, 340 Sepsis, 42, 166, 340 Septic, 41, 215, 216, 340 Septum, 194, 197, 250, 273, 280, 340 Septum Pellucidum, 340 Sequencing, 18, 56, 330, 340, 346 Sequester, 282, 340 Serine, 51, 193, 288, 334, 340, 348
Serologic, 146, 341 Serotonin, 163, 176, 199, 327, 336, 341, 349 Serous, 295, 307, 341 Serum, 17, 18, 21, 32, 124, 129, 169, 170, 267, 270, 284, 288, 308, 312, 315, 341, 350 Sex Characteristics, 266, 341, 346 Sex Determination, 243, 341 Shock, 9, 20, 41, 101, 137, 281, 341, 349 Sick Sinus Syndrome, 72, 341 Side effect, 173, 184, 188, 206, 229, 231, 266, 269, 276, 292, 341, 348 Signal Transduction, 7, 10, 14, 26, 190, 278, 281, 310, 341 Sinoatrial Node, 341 Skeleton, 265, 298, 312, 332, 341 Skull, 341, 346 Sleep apnea, 211, 212, 342 Small intestine, 292, 306, 311, 342 Social Environment, 335, 342 Social Work, 142, 342 Sodium, 13, 199, 210, 268, 277, 292, 321, 322, 328, 342 Soft tissue, 277, 341, 342 Solid tumor, 270, 292, 342 Solitary Nucleus, 274, 342 Solvent, 51, 275, 297, 303, 342 Soma, 342 Somatic, 53, 69, 266, 294, 316, 318, 327, 342 Somatic cells, 53, 316, 318, 342 Somatostatin, 211, 212, 323, 342 Sorbitol, 163, 164, 175, 176, 188, 199, 205, 267, 342 Sound wave, 143, 154, 286, 336, 342, 350 Spasm, 69, 171, 206, 272, 343 Spasticity, 274, 343 Specialist, 251, 291, 343 Species, 18, 54, 57, 76, 166, 174, 288, 290, 296, 305, 306, 311, 313, 316, 318, 319, 325, 335, 336, 343, 344, 349, 350, 352, 353 Specificity, 208, 210, 267, 278, 343 Spectrin, 293, 343 Spectrum, 15, 56, 59, 90, 343 Sperm, 283, 337, 343 Spinal cord, 273, 274, 277, 282, 296, 300, 304, 316, 317, 321, 327, 336, 343, 345 Spinal Cord Diseases, 300, 304, 343 Spinal Nerves, 327, 343 Spleen, 269, 288, 315, 339, 343 Spontaneous Abortion, 221, 343 Sporadic, 29, 190, 338, 343 Squalene Synthetase, 57, 343 Stabilization, 20, 343
Index 371
Staging, 339, 343 Statistically significant, 52, 344 Steady state, 16, 43, 344 Steatosis, 21, 241, 344 Steel, 186, 283, 344 Stem Cells, 207, 344 Stent, 79, 91, 344 Steroids, 287, 302, 344 Stimulant, 290, 292, 306, 312, 317, 344 Stimulus, 14, 45, 50, 219, 286, 293, 297, 310, 311, 336, 344, 347 Stomach, 188, 265, 291, 296, 300, 301, 302, 306, 312, 315, 321, 327, 328, 336, 342, 343, 344 Strand, 330, 344 Stroke, 7, 157, 181, 191, 196, 210, 236, 279, 280, 344 Stroke Volume, 181, 210, 279, 344 Styrene, 186, 339, 344 Subacute, 9, 309, 344 Subclinical, 111, 114, 309, 340, 344 Subcutaneous, 266, 293, 314, 344 Subspecies, 343, 344 Substance P, 317, 340, 344 Substrate, 6, 8, 21, 26, 33, 47, 87, 99, 188, 280, 337, 345 Sudden cardiac death, 12, 83, 102, 107, 130, 345 Sudden death, 8, 12, 36, 77, 92, 101, 111, 150, 161, 183, 225, 345 Sulfur, 297, 317, 345 Superantigens, 219, 345 Superior vena cava, 181, 277, 341, 345 Superoxide, 124, 345 Superoxide Dismutase, 124, 345 Supplementation, 130, 132, 133, 345 Suppression, 23, 50, 62, 345, 353 Supraspinal, 274, 345 Supraventricular, 191, 196, 345 Surface Plasmon Resonance, 20, 345 Survival Rate, 208, 345 Sympathetic Nervous System, 106, 196, 270, 274, 345 Sympathomimetic, 210, 290, 296, 317, 323, 345 Symphysis, 333, 346 Synapsis, 346 Synaptic, 58, 193, 341, 346 Synchrony, 172, 178, 346 Synergistic, 6, 16, 37, 164, 179, 187, 346 Systemic disease, 182, 346 Systole, 35, 179, 180, 181, 194, 197, 346
Systolic, 3, 19, 28, 35, 48, 69, 74, 95, 96, 103, 122, 172, 174, 178, 194, 213, 307, 346 Systolic heart failure, 48, 346 T Tachycardia, 35, 47, 48, 58, 72, 73, 86, 91, 101, 103, 108, 186, 226, 292, 346 Taurine, 121, 133, 138, 346 Telangiectasia, 242, 346 Temporal, 9, 44, 346 Teratogenic, 54, 291, 346 Teratogenicity, 54, 346 Terminator, 346, 353 Testosterone, 336, 346 Tetracycline, 31, 42, 56, 346 Thalamic, 273, 346 Thalamic Diseases, 273, 346 Thalassemia, 13, 346 Therapeutics, 21, 57, 188, 190, 214, 230, 347 Thermal, 41, 44, 292, 322, 330, 347 Thiamine, 279, 347 Thigh, 298, 304, 347 Thoracic, 82, 92, 95, 97, 101, 103, 112, 114, 117, 277, 316, 347, 353 Thorax, 265, 345, 347 Threonine, 10, 51, 193, 334, 340, 347 Threshold, 196, 297, 307, 347 Thrombin, 298, 329, 333, 347 Thrombocytes, 329, 347 Thrombocytopenia, 269, 347 Thromboembolism, 171, 347 Thrombolytic, 329, 347 Thrombomodulin, 333, 347 Thrombosis, 120, 206, 333, 344, 347 Thromboxanes, 272, 347 Thrombus, 114, 121, 287, 309, 320, 329, 347 Thymus, 138, 308, 315, 347 Thyroid, 54, 307, 311, 325, 326, 347, 350 Thyroid Gland, 307, 325, 326, 347 Tin, 280, 327, 329, 347 Tissue Culture, 41, 348, 352 Tissue Extracts, 22, 348 Tissue Plasminogen Activator, 8, 348 Tolerance, 14, 179, 219, 265, 302, 348 Tomography, 147, 214, 316, 348 Tooth Preparation, 266, 348 Topical, 297, 306, 348 Torsion, 103, 309, 348 Toxicity, 48, 54, 57, 188, 280, 292, 308, 348 Toxicology, 79, 124, 238, 348 Toxins, 271, 278, 294, 309, 348 Tracer, 120, 154, 348
372
Cardiomyopathy
Trachea, 278, 328, 347, 348 Traction, 283, 348 Transcriptase, 338, 348 Transcription Factors, 28, 40, 49, 62, 193, 337, 348 Transduction, 26, 161, 341, 348 Transfection, 40, 42, 276, 349 Transfer Factor, 308, 349 Transferases, 303, 349 Transfusion, 13, 349 Transgenes, 56, 349 Translation, 36, 45, 349 Translational, 18, 44, 349 Translocation, 6, 21, 193, 349 Transmitter, 265, 273, 311, 316, 323, 349 Transplantation, 88, 101, 111, 155, 160, 161, 183, 208, 214, 219, 283, 308, 313, 349 Trauma, 41, 275, 296, 304, 321, 346, 349 Trigger zone, 311, 349 Triglyceride, 34, 63, 70, 307, 349 Trimetazidine, 110, 349 Troglitazone, 180, 349 Tropomyosin, 24, 61, 64, 80, 86, 116, 198, 319, 349 Troponin, 8, 10, 36, 38, 42, 43, 61, 62, 64, 66, 67, 68, 75, 80, 86, 90, 96, 104, 225, 319, 349 Troponin C, 64, 349 Troponin T, 61, 349 Trypanosomiasis, 326, 349 Tryptophan, 10, 33, 284, 341, 349 Tuberculosis, 220, 286, 315, 350 Tuberous Sclerosis, 243, 350 Tumor marker, 276, 350 Tumor Necrosis Factor, 28, 41, 44, 49, 93, 350 Type 2 diabetes, 52, 63, 103, 206, 210, 219, 350 Tyrosine, 51, 333, 350 U Ubiquinone, 176, 177, 350 Ubiquitin, 198, 350 Ultrasound test, 142, 350 Unconscious, 270, 308, 350 Urea, 312, 350 Uremia, 4, 213, 218, 312, 336, 350 Urethane, 186, 350 Urethra, 333, 350, 351 Uric, 268, 335, 350 Urinary, 323, 348, 350, 353 Urinary Plasminogen Activator, 348, 350 Urinate, 260, 350
Urine, 141, 206, 260, 272, 276, 287, 288, 292, 305, 312, 321, 323, 334, 350, 351 Uterus, 282, 289, 295, 317, 324, 351 V Vaccine, 266, 334, 351 Valves, 41, 185, 189, 283, 325, 351 Vasa Nervorum, 204, 351 Vascular endothelial growth factor, 170, 351 Vascular Resistance, 47, 210, 269, 298, 351 Vasculitis, 183, 351 Vasoactive, 139, 196, 351 Vasoconstriction, 47, 196, 292, 296, 351 Vasodilatation, 312, 322, 351 Vasodilation, 270, 322, 351 Vasodilator, 269, 271, 277, 298, 300, 306, 318, 320, 322, 349, 351 Vasomotor, 297, 351 Vector, 161, 183, 201, 348, 351 Vein, 120, 143, 154, 181, 270, 273, 309, 311, 323, 345, 351 Vena, 351 Venous, 175, 181, 187, 209, 211, 272, 273, 289, 304, 322, 323, 333, 351 Venous blood, 181, 304, 351 Venous Pressure, 175, 209, 211, 351 Ventral, 62, 307, 330, 343, 351 Ventricular Dysfunction, 18, 36, 45, 80, 108, 114, 191, 196, 293, 351 Ventricular fibrillation, 135, 186, 351 Ventricular Function, 15, 24, 30, 59, 105, 124, 172, 195, 218, 352 Ventricular Remodeling, 32, 40, 45, 46, 75, 84, 352 Venules, 277, 279, 295, 318, 352 Verapamil, 155, 192, 226, 300, 352 Vertigo, 299, 352 Vesicular, 273, 352 Veterinary Medicine, 237, 352 Vimentin, 198, 352 Viral, 28, 48, 62, 166, 169, 182, 198, 294, 309, 348, 352, 353 Virulence, 274, 348, 352 Virus, 16, 66, 81, 104, 160, 161, 169, 171, 183, 265, 274, 295, 301, 310, 329, 348, 352 Viscera, 342, 352 Visceral, 6, 57, 94, 137, 274, 313, 327, 352 Visceral Afferents, 274, 352 Viscosity, 178, 338, 352 Vitreous Body, 337, 352 Vitreous Hemorrhage, 291, 352 Vitro, 15, 20, 36, 40, 61, 352
Index 373
Vivo, 9, 10, 11, 14, 15, 16, 17, 20, 21, 24, 28, 32, 36, 41, 42, 43, 45, 62, 70, 87, 161, 181, 183, 199, 309, 347, 352 W Welchii, 328, 352 White blood cell, 271, 276, 283, 313, 314, 315, 319, 329, 352 Windpipe, 328, 347, 352 Withdrawal, 7, 353 World Health, 63, 262, 353 Wound Healing, 299, 316, 353
X Xanthine, 64, 268, 353 Xanthine Oxidase, 64, 268, 353 Xenograft, 270, 353 X-ray, 141, 145, 261, 262, 270, 281, 285, 299, 316, 323, 335, 339, 353 Y Yeasts, 300, 328, 353 Z Zidovudine, 81, 353 Zygote, 286, 353 Zymogen, 333, 353
374
Cardiomyopathy
Index 375
376
Cardiomyopathy
