HEART FAILURE 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., 1960Heart Failure: 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: 0-597-83974-3 1. Heart Failure-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 heart failure. 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 HEART FAILURE ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Heart Failure................................................................................. 6 The National Library of Medicine: PubMed ................................................................................ 67 CHAPTER 2. NUTRITION AND HEART FAILURE ............................................................................ 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Heart Failure.............................................................................. 113 Federal Resources on Nutrition ................................................................................................. 119 Additional Web Resources ......................................................................................................... 120 CHAPTER 3. ALTERNATIVE MEDICINE AND HEART FAILURE ...................................................... 123 Overview.................................................................................................................................... 123 National Center for Complementary and Alternative Medicine................................................ 123 Additional Web Resources ......................................................................................................... 139 General References ..................................................................................................................... 146 CHAPTER 4. DISSERTATIONS ON HEART FAILURE ........................................................................ 147 Overview.................................................................................................................................... 147 Dissertations on Heart Failure .................................................................................................. 147 Keeping Current ........................................................................................................................ 150 CHAPTER 5. CLINICAL TRIALS AND HEART FAILURE .................................................................. 151 Overview.................................................................................................................................... 151 Recent Trials on Heart Failure .................................................................................................. 151 Keeping Current on Clinical Trials ........................................................................................... 172 CHAPTER 6. PATENTS ON HEART FAILURE................................................................................... 175 Overview.................................................................................................................................... 175 Patents on Heart Failure............................................................................................................ 175 Patent Applications on Heart Failure ........................................................................................ 201 Keeping Current ........................................................................................................................ 229 CHAPTER 7. BOOKS ON HEART FAILURE ...................................................................................... 231 Overview.................................................................................................................................... 231 Book Summaries: Federal Agencies............................................................................................ 231 Book Summaries: Online Booksellers......................................................................................... 238 The National Library of Medicine Book Index ........................................................................... 245 Chapters on Heart Failure.......................................................................................................... 247 CHAPTER 8. MULTIMEDIA ON HEART FAILURE ........................................................................... 249 Overview.................................................................................................................................... 249 Video Recordings ....................................................................................................................... 249 Bibliography: Multimedia on Heart Failure .............................................................................. 250 CHAPTER 9. PERIODICALS AND NEWS ON HEART FAILURE ........................................................ 253 Overview.................................................................................................................................... 253 News Services and Press Releases.............................................................................................. 253 Newsletters on Heart Failure..................................................................................................... 258 Newsletter Articles .................................................................................................................... 259 Academic Periodicals covering Heart Failure ............................................................................ 260 CHAPTER 10. RESEARCHING MEDICATIONS ................................................................................. 263 Overview.................................................................................................................................... 263 U.S. Pharmacopeia..................................................................................................................... 263 Commercial Databases ............................................................................................................... 268 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 273 Overview.................................................................................................................................... 273
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NIH Guidelines.......................................................................................................................... 273 NIH Databases........................................................................................................................... 275 Other Commercial Databases..................................................................................................... 277 APPENDIX B. PATIENT RESOURCES ............................................................................................... 279 Overview.................................................................................................................................... 279 Patient Guideline Sources.......................................................................................................... 279 Finding Associations.................................................................................................................. 291 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 295 Overview.................................................................................................................................... 295 Preparation................................................................................................................................. 295 Finding a Local Medical Library................................................................................................ 295 Medical Libraries in the U.S. and Canada ................................................................................. 295 ONLINE GLOSSARIES................................................................................................................ 301 Online Dictionary Directories ................................................................................................... 307 HEART FAILURE DICTIONARY .............................................................................................. 309 INDEX .............................................................................................................................................. 403
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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 heart failure 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 heart failure, 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 heart failure, 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 heart failure. 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 heart failure, 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 heart failure. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON HEART FAILURE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on heart failure.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and heart failure, 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 “heart failure” (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: •
Pathophysiology of Congestive Heart Failure in ESRD Source: ANNA Journal. American Nephrology Nurses Association Journal. 23(5): 457463. October 1996. Contact: Available from American Nephrology Nurses' Association. East Holly Avenue, Box 56, Pitman, NJ 08071-0056. (609) 256-2320. Summary: Congestive heart failure (CHF) represents the inability of the heart to pump enough blood to meet tissue requirements for oxygen, resulting in a discrepancy between myocardial oxygen supply and demand. It can result from any clinical situation that alters myocardial performance, including end-stage renal disease (ESRD). This article describes the pathophysiology of CHF, the major signs and symptoms, medical management, and nursing interventions in patients with ESRD. One table summarizes
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the signs and symptoms of digitalis toxicity; a second describes four types of vasodilators used to manage CHF. An algorithm of patient care is also provided. 1 figure. 2 tables. 17 references. (AA-M). •
Cross-Sectional Study of the Prevalence and Clinical Correlates of Congestive Heart Failure Among Incident U.S. Dialysis Patients Source: American Journal of Kidney Diseases. 38(5): 992-1000. November 2001. Contact: Available from W.B. Saunders Company. Periodicals Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Website: www.harcourthealth.com. Summary: Epidemiological characteristics of congestive heart failure (CRF) have not been well studied in patients with end stage renal disease (ESRD). This article reports on a study that evaluated the prevalence and clinical correlates of CHF using data from Wave 2 of the US Renal Data System Dialysis Morbidity and Mortality Study, a national random sample of incident hemodialysis and peritoneal dialysis patients in 1996 and 1997 (n = 4,024). CHF was recorded as present in 36 percent of patients. In multivariate analysis, age, female sex, hypertension, diabetes, measures of atherosclerosis, and structural cardiac abnormalities were significantly associated with the presence of CHF. Elevated serum (blood) phosphate level and serum calcium level were associated with significantly more CHF, as were low serum albumin (protein) and low serum cholesterol levels. Of elements of pre ESRD care, frequent visits to a nephrologist or dietitian were associated with significantly lower odds of CHF at the start of ESRD compared with less frequent visits. This national study shows the association of several measures of atherosclerosis and cardiac (heart) abnormalities with the presence of CHF at the start of dialysis therapy. The data identify serum albumin as a strong disease correlate and suggest that elevated serum calcium and phosphate levels may be potential risk factors for CHF. This study also suggests that frequent specialist care during this critical period may have a favorable impact on the prevalence of CHF at the start of ESRD. 2 figures. 4 tables. 25 references.
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Cause and Management of Heart Failure in Patients with Chronic Renal Disease Source: Seminars in Nephrology. 21(1): 3-12. January 2001. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Heart failure occurs in 40 percent of patients with end stage renal disease (ESRD) and is a major determinant of mortality (death). Heart failure occurs in patients with left ventricular systolic dysfunction (dilated left ventricle) as well as those with a normal resting ejection fraction (nondilated left ventricle). This article describes the cause of heart failure among patients with ESRD and the effect of heart failure on survival. The authors also discuss the impact of renal failure on the medical management of these patients. The prognosis of patients with ESRD who develop heart failure is poor. Treatment modalities in this population involve risk reduction, medication directed at symptoms and disease progression, and dialysis, where appropriate, with careful attention to volume management. There are few data evaluating the use of specific pharmacologic therapies in patients with renal failure. As a result, many of the recommendations offered in this article are from data derived from patients without ESRD. 3 figures. 84 references.
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Albuminuria and Risk of Cardiovascular Events, Death, and Heart Failure in Diabetic and Nondiabetic Individuals Source: JAMA. Journal of the American Medical Association. 286(4): 421-426. July 25, 2001. Summary: This article describes a study that estimated the risk of cardiovascular (CV) events in high risk people with and without diabetes who had microalbuminuria and determined whether levels of albuminuria below the microalbuminuria threshold increase CV risk. Data were collected from people enrolled in the Heart Outcomes Prevention Evaluation Study. The study population consisted of 3,498 people with diabetes and 5,545 people without diabetes. Participants were followed up for a median of 4.5 years. Main outcome measures were cardiovascular events, all cause death, and hospitalization for congestive heart failure. The study found that microalbuminuria was detected in 1,140 of those with diabetes and 823 of those without diabetes at baseline. Microalbuminuria increased the adjusted relative risk (RR) of major CV events, all cause death, and hospitalization for congestive heart failure. Similar RRs were seen for participants with or without diabetes, even after adjusting for other CV risk factors. Compared with the lowest quartile of urine albumin/creatinine ratio (ACR), the RRs of the primary aggregate endpoint in the second quartile was 1.11; third quartile, 1.38; and fourth quartile, 1.97. For every 0.4 milligram/mmol increase in ACR level, the adjusted hazard of major CV events increased by 5.9 percent. The article concludes that the results indicate that any degree of albuminuria is a risk factor for CV events in people with or without diabetes. The risk increases with the ACR, starting well below the microalbuminura cutoff. Screening for albuminuria identifies people at high risk for CV events. 1 figure. 3 tables. 47 references. (AA-M).
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Angiotensin-Converting Enzyme Inhibitor Use in Older Patients with Heart Failure and Renal Dysfunction Source: JAGS. Journal of the American Geriatrics Society. 47(3): 302-308. March 1999. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423. Summary: This article reports on a study undertaken to examine the relationship between angiotensin converting enzyme (ACE) inhibitor use and clinical outcomes among recently hospitalized patients with congestive heart failure (CHF) and coexisting renal insufficiency. The study included a total of 1,076 hospital survivors identified from a consecutive series of CHF inpatients. Patients were followed prospectively for 6 months after hospital discharge to track mortality, hospital readmission, and quality of life. Clinical outcomes were stratified by ACE inhibitor use among those with renal dysfunction and among the remaining patients. ACE inhibitor use was lower among 187 patients with renal dysfunction than among 889 patients with preserved function (41 versus 69 percent). Age and sex were among the significant determinants of drug use in both groups. After adjustment for covariables, ACE inhibitor use among those with abnormal renal function was not associated with a lower risk for death or readmission, or better quality of life. The authors conclude that convincing evidence of clinical benefit from ACE inhibitor use is not readily detectable among a sample of 187 unselected older patients with CHF and moderate or severe renal insufficiency. 4 tables. 36 references. (AA-M).
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Congestive Heart Failure in Type 2 Diabetes: Prevalence, Incidence, and Risk Factors Source: Diabetes Care. 24(9): 1614-1619. September 2001.
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Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article describes a study that estimated the prevalence and incidence of congestive heart failure (CHF) in populations with and without type 2 diabetes and identified risk factors for diabetes associated CHF. The study searched the inpatient and outpatient electronic medical records of 9,591 people diagnosed with type 2 diabetes before January 1, 1997 and those of an age and sex matched control group without diabetes for a diagnosis of CHF. Among those without a baseline diagnosis of CHF, the study searched forward for 30 months for incident cases of CHF. Multiple logistic regression models were constructed to identify risk factors for both prevalent and incident CHF. The study found that CHF was prevalent in 11.8 percent of people with diabetes and 4.5 percent of control subjects at baseline. Incident cases of CHF were observed in 7.7 percent of people with diabetes who were free of CHF at baseline and in 3.4 percent of control subjects. In people with diabetes, age, diabetes duration, insulin use, ischemic heart disease, and elevated serum creatinine were independent risk factors for both prevalent and incident CHF. Better glycemic control at baseline and improved glycemic and blood pressure control at follow up predicted the development of CHF. The article concludes that the issue of why insulin use and better glycemic control both at baseline and follow up independently predicted CHF deserves further study. 1 appendix. 1 figure. 3 tables. 40 references. (AA-M). •
Chronic Heart Failure Source: Postgraduate Medicine. 109(4): 139-140. April 2001. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: This review article uses a question and answer format to provide heart attack survivors with information on heart failure. This condition is most commonly caused by damage to the heart as a result of a heart attack. Symptoms of heart failure include shortness of breath, weight gain, ankle swelling, fatigue, and increased nocturnal urination. Diagnosis is based on physical examination and diagnostic test findings. People who have heart failure can take various actions to help their heart work better, including avoiding excessive use of salt or salty food, quitting smoking, losing weight, resting during the day if possible, watching for sudden weight gain, and taking prescribed medications. The article also outlines the common causes of congestive heart failure, a more serious form of heart failure, and lists signs and symptoms indicating the need to seek immediate medical care.
Federally Funded Research on Heart Failure The U.S. Government supports a variety of research studies relating to heart failure. 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. 2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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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 heart failure. 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 heart failure. The following is typical of the type of information found when searching the CRISP database for heart failure: •
Project Title: ADENOVIRAL GENE TRANSFER OF CA2+ ATPASE IN HEART FAILURE Principal Investigator & Institution: Hajjar, Roger J.; Assistant Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 10-FEB-1997; Project End 31-MAR-2006 Summary: (provided by applicant): Heart failure is characterized by a number of abnormalities at the cellular level in the various steps of excitation-contraction coupling. One of the key abnormalities in both human and experimental heart failure is a defect in sarcoplasmic reticulum (SR) function which is associated with abnormal intracellular calcium handling. Deficient SR Ca2+ uptake during relaxation has been identified in failing hearts from both humans and animal models and has been associated with a decrease in the expression and activity of SR Ca2+-ATPase (SERCA2a). The goals of the First Award (R29) were 1) to validate the use of adenoviral gene transfer in the rat model of heart failure and 2) to test the hypothesis that increasing the expression of SERCA2a will restore contractility and normalize intracellular calcium cycling in this model of heart failure. These goals have been specifically achieved during the tenure of the grant. To further extend these results that have clinical promise for the treatment of congestive heart failure, we will test the following hypotheses: 1) that the long-term overexpression of SERCA2a will improve survival and induce ventricular and metabolic remodeling in a rat model of heart failure; 2) overexpression of SERCA2a during compensated hypertrophv will delay the onset of the transition to heart failure; 3) decreasing phospholamban expression by antisense strategies will enhance SR Ca2+ATPase function in failing hearts and restore function, and 4) the beneficial effect observed by improving calcium handling in heart failure is specific to SERCA2a. To test these hypotheses, we will use viral vectors to express wild-type and mutant forms of specific signaling molecules in cardiocytes in vitro and in vivo. In Specific Aim 1, we will develop and characterize ventricular specific vectors carrying SERCA2a and transduce ventricles from hypertrophied and failing rat hearts. In Specific Aim 2, we will examine the effects of decreasing phospholamban using antisense strategies on survival and remodeling in hypertrophied and failing rat hearts. In Specific Aim 3, we will study the effect of improving calcium handling in failing rat hearts by overexpressing Na+/Ca2+ exchanger and parvalbumin in a rat model of heart failure. Understanding the role of calcium regulation in cardiocyte dysfunction and developing approaches to local modulation of these pathways through somatic gene transfer, may provide novel therapeutic approaches for the management of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADENYLYL CYCLASE VIII GENE THERAPY FOR CHF Principal Investigator & Institution: Hammond, H Kirk.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006
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Summary: Heart failure is the only cardiovascular disease that is increasing in prevalence and the outlook for a patient with dilated heart failure remains dismal despite recent advances in therapy. The key abnormality is the major focus of this Project. We have shown that the amount of adenylyl cyclase (AC) sets a limit on cAMP production. We then showed that over-expression of AC increases cardiac contractile function in transgenic mice. When AC is expressed in the setting of murine cardiomyopathy, cardiac function and survival are improved. Finally, we recently demonstrated that cardiac AC expression can be increased in a manner that can be applied clinically-through intracoronary delivery of an adenovirus encoding AC. The effects on LV function and cAMP generating capacity after intracoronary delivery are long-lasting and not associated with deleterious effects. These studies were conducted using AC type VI, a major isoform in mammalian heart. Cardiac-directed expression of ACVI or ACVIII, an isoform more typically found in brain than heart, shows similar favorable effects on cardiac contractility. But ACVIII exhibits unique properties. For example, compared to ACVI, ACVIII is less responsive to beta-adrenergic receptor (betaAR) stimulation, a potential advantage in the setting high catecholamine levels associated with congestive heart failure. We propose a gene therapy for heart failure. First, we will perform the necessary toxicology studies and bridging preclinical studies to support a Phase1/Phase 2 clinical trial of ACVIII gene therapy for severe heart failure (completed in the first funding year). We then will perform the clinical trial using intracoronary delivery of an adenovirus encoding human ACVIII for the treatment of dilated Class III/IV congestive heart failure (completed mid-way through Year 3). In the later phase of the award we will study other genes that might increase contractility and favorably influence symptoms and survival in heart failure. These studies will provide preclinical data sufficient to support a second IND filing so that the second Phase 1/Phase 2 clinical trial could be conducted in Year 4 and 5. A prime candidate is sarcoplasmic reticulum Ca2+ ATPase (SERCA2a). Hypotheses: 1. Intracoronary delivery of an adenovirus encoding ACVIII will improve heart function and reduce symptoms in patients with Class III/IV congestive heart failure. 2. Intracoronary delivery of an adenovirus encoding Ca2+ ATPase (SERCA2a) will improve heart function and reduce symptoms in patients with Class III/IV congestive heart failure. 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 2001; 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
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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 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: ALPHA-MYOSIN HEAVY CHAIN GENE REPRESSION & HEART FAILURE Principal Investigator & Institution: Gupta, Mahesh P.; Associate Professor; Surgery; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by the applicant): The broad objective of this application is to determine the molecular mechanisms behind alpha-MHC down-regulation that occurs during heart failure. Recent data obtained from both animals and humans indicate a considerable loss of alpha-MHC gene product. However, the mechanism behind alphaMHC down-regulation during heart failure remains virtually unknown. Recently, the PI has cloned and characterized a single-strand DNA-binding protein (PNRB) that plays a repressor role in gene transcription. Interestingly, the PI found that PNRB binds not only to an essential cis-regulatory element of the alpha-MHC gene but also to the coding region of alpha-MHC mRNA. The RNA oligonucleotide corresponding to this coding region has the ability to specifically pull down PNRB from cardiac nuclear extract. Furthermore, cellular levels of PNRB are found to be tremendously high in failing hearts. In light of these observations, the PI believes that PNRB plays a dual role, impairing both transcription and translational regulation of alpha-MHC gene expression in overloaded hearts. In this proposal, experiments have been designed to further explore the significance of PNRB in the control of alpha-MHC expression during heart failure. The PI will examine the role of PNRB in the transcription and translation of the alpha-MHC-reporter gene. The PI will also analyze the physiological significance of PNRB in alpha-MHC expression in a while heart preparation, and on the contractile characteristics of a failing heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AN ARTIFICIAL MYOCARDIUM FOR PEDIATRIC SUPPORT Principal Investigator & Institution: Stewart, Robert B.; Abiomed, Inc. 22 Cherry Hill Dr Danvers, Ma 01923 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2004
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Summary: (provided by applicant): The ultimate objective of this proposal is the commercialization of a pediatric ventricular assist device (VAD). Although, VADs, both implantable and paracorporeal, have become an important surgical option for adult patients with myocardial failure unresponsive to less aggressive therapy, no VADs are commercially available for short-term use in children or small infants who are critically ill with heart failure. This may be primarily due to the fact that the potential number of total cases remains small, especially in regard to the high costs necessary for the development of a viable commercially available product. An aggressive product development program for a pediatric VAD is proposed here. The end-point of the program will be an FDA submission for the first ever U.S. clinical trial for a pediatric VAD to be tested at a leading pediatric cardiac surgical center. The clinical indication for the device will be for temporary use either to allow myocardial healing and/or recovery (so-called bridge-to-recovery (B2R)), or to provide adequate blood flow in patients suffering from irreversible heart failure while awaiting heart transplantation (so-called bridge-to-transplantation (B2T)). The VAD being developed here will have several advantages over the current method used for short-term pediatric cardiac support (i.e., centrifugal pumps, usually with extracorporeal membrane oxygenation (ECMO)). The design chosen will provide pulsatile flow without issues related to either blood volume or thrombus formation. The Phase I study will demonstrate feasibility of the VAD design. Phase II will primarily involve readiness testing and detailed animal studies to support an FDA approved Investigational Device Exemption (IDE). This effort will be accomplished in tandem with a leading pediatric cardiac team at Miami Children's Hospital, who will be pivotal in the planning of the initial clinical trial. 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 2001; 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
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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 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: BONE MARROW ANGIOBLASTS FOR CARDIAC REGENERATION Principal Investigator & Institution: Itescu, Silviu; Assistant Professor; Surgery; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Congestive heart failure remains a major public health problem, and is frequently the result of left ventricular remodeling after myocardial infarction. We have recently shown that human adult bone marrow contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to induce infarct bed neovascularization after experimental myocardial infarction. The induction of neovascularization in the peri-infarct period results in protection of cardiomyocytes against apoptosis, induction of cardiomyocyte proliferation and regeneration, long-term salvage and survival of viable myocardium, prevention of left ventricular remodeling and sustained improvement in cardiac function. Our striking observation that neovascularization of acutely ischemic myocardium results in regeneration of endogenous cardiomyocytes suggests that a similar process could be induced in myocardium exposed to chronic ischemia, however no information exists to date regarding whether bone marrowderived angioblasts could reverse established heart failure and myocardial fibrosis. If similar effects could be achieved by angioblast infusion in an animal model of chronic ischemia and established ventricular remodelling and scarring, this would provide a potential new therapeutic modality for the treatment of established heart failure. In the first aim of this proposal we will specifically establish an animal model of chronic heart failure following ischemia and investigate whether angioblast-dependent neovascularization can result in myocardial regeneration and improvement in cardiac function. In the second aim, we will examine the role of specific CXC chemokines in angioblast migration to chronically ischemic myocardium. We will then seek to develop strategies that enable manipulation of interactions between CXC chemokines and their receptors in order to increase selective angioblast trafficking to chronically ischemic myocardium, promote vasculogenesis, and augment myocardial regeneration and functional improvement. In the final aim we will evaluate whether concomitant use of bone marrowderived angioblasts together with autologous mesenchymal stem cells or
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Heart Failure
pharmacologic agents may provide synergistic, additive benefit in terms of cardiomyocyte regeneration and cardiac function. We believe that gaining an understanding of these issues will prove to be of critical importance in order to be able to rationally design and develop strategies for human clinical trials using autologous bone marrow-derived endothelial progenitors in the treatment of chronic heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CA TRANSPORTER EXPRESSION IN HYPERTROPHY & HEART FAILURE Principal Investigator & Institution: Samarel, Allen M.; Professor; Medicine; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 10-JAN-2000; Project End 31-DEC-2003 Summary: A 5-year research program is outlined with the broad, long-term objective of elucidating the molecular mechanisms responsible for altered Ca2+ transporter gene expression in patients with cardiac hypertrophy and heart failure. There is now substantial evidence to indicate that expression levels of SERCA2 and NCX1, the major Ca2+ transporters in cardiac muscle, are profoundly altered in the failing human ventricular myocardium. These changes may result in reduced contractile function and increased susceptibility to ventricular arrhythmias. However, the underlying intracellular me4chanisms responsible for these changes, and the signal transduction pathways involved are only now being elucidated. Four specific aims are outlined to clarify these mechanisms in cultured cardiomyocytes, and related them to what may be occurring in hypertrophy and heart failure in experimental animals and man. First, previous work and preliminary data indicate a critical role of PKC activation in SERCA2 down-regulation during hypertrophy and heart failure. We will therefore use molecular biological techniques to over- express and down-regulate specific PKC isozymes to ascertain which PKC isozymes is responsible. Second, we will characterize the [Ca2+]i and Ras-dependent signaling pathways that regulate SERCA2 gene expression. Studies will focus on the non-receptor protein tyrosine kinase PYK2 that is activated by [Ca2+]i and PKC, and that may link G1- coupled receptor activation to the Ras-Raf-MEK-ERK protein kinase cascade. Third, preliminary data indicate that the 3' untranslated region of the SERCA2 mRNA regulates its stability in response to mechanical and neurohormonal stimuli that activate PKCs. Therefore, a series of experiments is outlined to define the cis-acting sequences and trans-acting factors that are involved. Fourth, we will test the hypothesis that activation of PKCs by either neurohormonal or mechanical stimuli (or their combination) up-regulates NXC1 mRNA and protein levels, and begin to analyze the signaling pathways responsible for these changes. The proposed experiments should substantially contribute to our understanding of the mechanisms responsible for altered Ca2+ transporter gene expression in heart failure Future therapeutic strategies targeted towards prevention or reversal of these changes require a thorough understanding of the responsible intracellular mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIAC ANGIOTENSIN: HYPERTROPHY AND FAILURE Principal Investigator & Institution: Lorell, Beverly H.; Associate Professor of Medicine; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-JUN-1995; Project End 31-JUL-2005 Summary: (the applicant's description verbatim): The angiotensin II type 2 (AT2) receptor predominates in the left ventricle (LV) in hypertrophy and heart failure, and
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AT2 receptor activation suppresses growth and promotes apoptosis in vitro. This project will test the overall hypothesis that AT2 receptor signaling in vivo mediates anti-growth and pro-apoptotic effects in pressure overload hypertrophy. We will use transgenic mice with ventricular targeted overexpression of the AT2 receptor driven by the MLC2V promoter which are subjected to ascending aortic stenosis. Functional consequences will be studied by echocardiography and hemodynamic measurements, analysis of isolated myocyte contraction and intracellular ion regulation using fluorescence video microscopy, and confocal microscopy analysis of in situ cell morphology and apoptosis. Signaling pathways will be studied by immunohistochemistry and immunoblotting using antibodies to specific signaling molecules and identification of phosphorylation state. The Specific Aims are: Aim 1. To determine if AT2 receptor overexpression in transgenic mice suppresses in vivo hypertrophic growth in response to chronic systolic pressure overload from aortic stenosis. We predict that AT2 receptor overexpression severely depresses the development of LV hypertrophy, and promotes the rapid development of heart failure and premature death. Aim 2. To test the hypothesis that AT2 receptor overexpression promotes myocyte apoptosis in mice with pressure overload. Apoptosis will be identified by in situ Tunel and ligase assays using confocal microscopy, and complementary measurement of cytochrome c leakage to the cytosol. Aim 3. To determine if AT2 receptor overexpression in vivo modifies myocyte contractile function, and interferes with Ang II mediated inotropy. These experiments will employ measurements of contractility as well as intracellular pH and Ca2+ in isolated mouse myocytes, and test the hypothesis that AT2 receptor activation suppresses the coupling of Ang II with forward Na+-H+ exchange. Aim 4. To determine if AT2 receptor overexpression in vivo activates the kinin-cGMP pathway. In vitro studies suggest that this system contributes to AT2 receptor signaling, but its contribution, if any, in the adult heart is not understood. Measurements will be made of cGMP levels and kininogenase activation in LV tissues (and atrial tissues in which the transgene is minimally expressed). In addition, the functional effects of inhibition of this pathway on cardiac growth and hemodynamic performance will be tested in vivo in mice with AT2 overexpression, in presence and absence of pressure overload. These integrated molecular physiology studies, which examine in vivo and cellular cardiac physiology, will provide new insights regarding cardioprotective versus deleterious effects of AT2 receptor activation in hypertrophy and heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIAC REGULATION
HYPERTROPHY
INDUCED
METABOLIC
GENE
Principal Investigator & Institution: Barger, Philip M.; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 08-APR-1998; Project End 31-JUL-2001 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
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Heart Failure
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 MAPPING OF VENTRICULAR DEFIBRILLATION Principal Investigator & Institution: Ideker, Raymond E.; Jeanne V. Marks Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-APR-1989; Project End 31-JUL-2007 Summary: (provided by applicant): While reentry is the mechanism of defibrillation failure for shocks well below the defibrillation threshold (DFT), recent optical and 3dimensional electrical mapping studies indicate that the mechanism of failure of near DFT strength shocks in normal hearts after 10 sec of ventricular fibrillation (VF) is the induction of at least 3 rapidly activating post-shock cycles arising from a focus where the shock field is weak. Thus it is crucial to understand how and why these focal rapid cycles arise and if the roles of the focal initiator and of the myocardial substrate in which the rapid cycles induce reentry are altered by cardiac disease or extended VF. This application proposes to accomplish three significant aims through the use of electrical and optical mapping to achieve this goal. Specific aim 1: Determine if at least 3 rapid focal ectopic cycles are necessary for the failure of near-DFT strength shocks in the presence of cardiac disease or long lasting VF. Because of the electrophysiologic alterations caused by old myocardial infarction, rapid pacing induced heart failure and longer lasting VF, it is possible that under these conditions fewer than 3 focal rapid cycles are required for defibrillation failure or even that foci are no longer observed. Specific aim 2: Determine the mechanism by which the focal cycles arise. Hypotheses will be tested that the rapid cycles are caused by delayed afterdepolarizations, early afterdepolarizations (EADs) or microreentry. Specific aim 3: Determine the mechanisms which cause the rapid focal cycles to arise in a particular cardiac location. The majority of foci in pigs arise within 4 mm of the epicardium. Hypotheses will be tested that the foci are located in this region because it is (1) within the M cell layer, (2) the boundary between the M cell and subepicardial layers, (3) the farthest extension of the Purkinje fibers, or (4) where the shock electric field is weakest. It is hoped that the basic knowledge gained about defibrillation mechanisms through these studies will lead to the improvement of defibrillation in patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIAC MAST CELL--ROLE IN PATHOGENESIS OF HEART FAILURE Principal Investigator & Institution: Janicki, Joseph S.; Professor; Animal Science; Auburn University at Auburn Auburn University, Al 36849 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 31-MAY-2003 Summary: Chronic ventricular volume overload leads to structural remodeling of the muscular, vascular and extracellular matrix components of the myocardium. However, the compensatory hypertrophy and ventricular dilatation induced by this condition ultimately has a detrimental affect on ventricular function, resulting in heart failure. A suitable explanation for this pathologic remodeling has not been established, although myocardial collagen fiber degradation represents a common pathway that could produce these adverse structural and architectural alterations. Fibrillar collagen provides the framework which interconnects the cardiomyocytes and blood vessels in the myocardium, thereby maintaining ventricular shape and size and contributing to tissue stiffness. These myocardial collagen fibers must be disrupted for ventricular dilatation, sphericalization and wall thinning to occur. Activation of myocardial metalloproteinases (i.e., collagenase) has been implicated in this adverse ventricular remodeling, however, virtually no studies have been performed to elucidate how this activation occurs in the heart. Recent evidence from our laboratory indicates that mast cell degranulation is responsible for collagenase activation in chronic volume overload. The proposed studies are designed to test the hypothesis that cardiac mast cells contribute to the pathologic ventricular remodeling which precedes the development of heart failure. Accordingly, this proposal will use infrarenal aortocaval fistula and myocardial infarction models of chronic volume overload in rats to examine the role of cardiac mast cells at the organ, tissue, and cellular levels. The specific aims of the proposal are 1) to determine: if cardiac mast cells are involved in the myocardial remodeling process; whether mast cell phenotype and/or protein expression change during this process; and mast cell sensitivity to cytokines, ANP, and other neuroendocrine hormones; 2) to assess the ability of mast cell secretory products to regulate cardiac mast cell density and the synthesis and degradation of the cardiac ECM as well as their effect on the interaction of cardiac myocytes and fibroblasts with the ECM; and 3) to determine whether pharmacological inhibition of the mast cell- induced MMP activation cascade will prevent the development of heart failure. These studies will utilize a variety of physiologic, morphologic, biochemical, and molecular techniques to characterize the role of cardiac mast cells in the ventricular remodeling at critical pathological stages in the development of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIAC NA-CA EXCHANGER: HYPERTROPHIC REGULATION Principal Investigator & Institution: Menick, Donald R.; Professor; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: The etiologies of late hypertrophy and heart failure are extremely complex but altered cellular calcium regulation appears to be a final common cause in both arrhythmogenesis and contractile dysfunction. The SR Ca2+-ATPase (SERCA) and sarcolemmal Na+-Ca2+ exchanger (NCX1) are two major transporters responsible for reducing [Ca2+]i to a low resting level during relaxation. SERCA expression and activity are decreased in hypertrophy and failure and we and others have shown that expression and activity in NCX1 is increased in this situation. Recent reports have demonstrated
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Heart Failure
that upregulation of the exchanger appears to be a critical link between contractile dysfunction and arrhythmogenesis. Additional studies have documented the cardioprotective effect resulting from inhibition of calcium influx via NCX1 in ischemia/reperfusion, digitalis toxicity and atrial fibrillation-induced shortening of atrial refractiveness. So far these results are solely based on acute studies and do not address long-term treatment. We discovered that inhibition of NCX1 calcium influx pathway (reverse mode) either by KB-R7943 or by lowering [Ca2+]o, resulted in the activation of signaling factors that leads to specific upregulation of the exchanger gene. This novel and exciting finding should have a profound impact on potential long-term treatment and places regulation of exchanger activity in a whole new light. The exchanger, whose activity is acutely sensitive to [Ca2+]o, [Ca2+]i, [Na+]i, and membrane potential (Em), may also act as a cellular rheostat that plays a role in the modulation of specific signal transduction pathways. Our hypothesis is that alteration of exchanger activity can directly activate signal transduction pathways resulting in changes in exchanger gene expression. This will be tested through the following aims: 1) Determine that the KBR induced activation of p38 and upregulation of NCX1 is directly mediated by the exchanger. 2) Determine whether changes in exchanger activity transduce the activation of signaling pathways by direct interaction or via changes in [Ca2+]i. 3) Identify factors interacting directly with the exchanger that mediate the activation of p38. 4) Identify the downstream factors in the signaling pathway mediating p38 activation. This work will allow us to better understand the role that exchanger activity plays in failure and provide a framework for therapeutic development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIOVASCULAR STIFFENING IN AGED PATIENTS WITH CHF Principal Investigator & Institution: Kass, David A.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Heart failure predominantly affects individuals of advanced age, and is currently reaching epidemic proportions. Nearly half the patients with symptoms of heart failure have preserved systolic ejection fraction (EF>50 percent), and are generally thought to suffer from ventricular diastolic dysfunction. However, most of these same individuals are over 65 years of age and have systolic hypertension, both factors that can themselves adversely impact on diastolic function. An additional mechanism that may prominently contribute to failure symptoms despite preservation of EF is ventricular-arterial stiffening. Vascular stiffening is common with aging, and results in increased arterial pulse pressure and systolic hypertension, both dominant risk factors for the development of coronary artery disease and heart failure. We have shown that ventricular systolic stiffening with or without cardiac hypertrophy accompanies progressive vascular stiffening with age. When combined, these changes can limit cardiac reserve capacity, enhance blood pressure fluctuations with daily activities of living, and limit coronary flow reserve. The studies in this proposal test the novel hypothesis that ventricular-vascular stiffening is a potent contributor to cardiac failure with preserved EF by reducing exercise capacity due to limited systolic reserve, enhancing blood pressure lability, and inducing abnormal coronary flow and myocardial energy balance with increased stress. The studies employ new methods for non-invasive quantitation of ventricular/vascular stiffening recently developed and validated in the P.I.'s laboratory. The first two specific aims test whether ventricularvascular stiffening is greater in patients with "non-systolic" heart failure versus a control group of similar age, blood pressure, hypertrophy, and sex, and tests its impact on
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blood pressure lability, reduced systolic reserve, and exercise performance. The third aim focuses on the impact of ventricular/vascular stiffening on coronary flow regulation and high energy phosphate metabolism. These studies test the influence of combined stiffening on cardiac supply/demand balance with stress. This research should provide major new insights regarding the pathophysiology of heart failure with preserved EF and specifically the importance of ventricular-vascular stiffening. This could lead to new therapeutic approaches to this difficult clinical problem that affects a growing aged patient population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIOVASCULAR STRESS OF SLEEP APNEA AND HEART FAILURE Principal Investigator & Institution: Schwartz, Alan R.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Sleep apnea is a common disorder associated with an increased risk of cardiovascular disease, and is particularly prevalent in heart failure patients. The cardiovascular risk of sleep apnea is likely to be amplified in the presence of heart failure since each disorder can aggravate the other. This proposal examines the interrelationship between sleep apnea and heart failure, and the mechanisms leading to cardiovascular stress when the two interact. Our proposal is predicated on the notion that sleep apnea increases cardiovascular stress, and further worsens left ventricular function in heart failure patients. Our major hypothesis is that a reciprocal interaction exists between sleep apnea and heart failure, wherein sleep-related disturbances in key mediators lead to acute and chronic increases in cardiovascular stress and worsening left ventricular function. To test this hypothesis, experiments are proposed in humans and murine models of sleep apnea and heart failure. In Specific Aims 1 and 2, heart failure patients will be intensively studied nocturnally to elucidate the mechanisms by which sleep apnea and its associated arousals and hypoxemic episodes increase cardiovascular stress acutely and perpetuate cardiovascular stress chronically. In Specific Aims 3 and 4, studies in novel murine models of chronic intermittent and sleepinduced hypoxia will examine the mechanisms in which sleep apnea and heart failure interact at the cardiac and central nervous system level. This potentially harmful interaction will be explored by assessing responses in: (a) novel mediators of cardiovascular stress (reactive oxygen species, cytokines, leptin, and insulin), (b) an important biomarker of acute and chronic cardiovascular stress (B-type natriuretic peptide, BNP), (c) cardiac tissue, and in (d) cardiac and CNS gene expression. The research plan will elucidate new mechanisms causing excess cardiovascular morbidity and mortality in heart failure, as well as provide new approaches to detect, monitor and treat sleep apnea in heart failure patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTRIBUTION OF ENERGY DEPLETION TO HUMAN HEART FAILURE Principal Investigator & Institution: Weiss, Robert G.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 19-JUL-1999; Project End 31-MAY-2003 Summary: (the applicant's description verbatim): A critical untested biochemical hypothesis of human heart failure, as specifically emphasized by the NHLBI Special
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Heart Failure
Emphasis Panel (SEP) on Heart Failure Research, is the Contribution of Energy Depletion to Heart Failure. This hypothesis suggests that energy transfer is reduced in congestive heart failure (CHF) and may limit contractile function. ATP is the biochemical fuel that sustains normal contractile function and creatine phosphate (Pcr) rapidly re-generates ATP via the creatine kinase (CK) reaction and is the major energy reserve in cardiac tissues. 31P magnetic resonance spectroscopy (MRS) is the only noninvasive means for directly studying cardiac biochemical energy metabolism. The investigators developed many of the 31P MRS techniques used today to quantify human cardiac CK metabolites and recent MRS techniques capable of detecting more subtle limitations in energy transfer. We propose here a close collaboration among experts in bioenergetics and novel imaging techniques with heart failure clinicians to combine for the first time biochemical investigations under physiological conditions with state-ofthe-art assessments of contractile function and robust clinical correlates to evaluate whether energy depletion is present and contributes mechanistically to human heart failure progression. The three specific aims are: 1. To test the hypothesis that the myocardial metabolite concentrations of the CK energy reserve system are reduced in proportion to heart failure severity and predict its progression. 2. To evaluate energy reserve in heart failure, we will test the hypothesis that the response of the cardiac creatine kinase energy reserve to modulations of myocardial energy demand differs in normal and failing human myocardium. 3.To evaluate a metabolic intervention, we will test the hypothesis that oral creatine supplementation can improve myocardial energetics and thereby improve contractile function, symptoms and exercise tolerance of patients with chronic congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF METABOLISM BY NO IN THE FAILING HEART Principal Investigator & Institution: Recchia, Fabio A.; Assistant Professor; Physiology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 04-FEB-2000; Project End 31-JAN-2004 Summary: A role for NO in the control of cardiac metabolism is receiving support from an increasing number of studies. We recently found that the acute blockade of NO synthase (NOS) in normal dogs and the fall in NO production during pacing induced heart failure are both associated with a switch from free fatty acids (FFA) to carbohydrate utilization by the heart. The mechanisms underlying these phenomena are unknown. This research proposal will determine the role of NO in the control of cardiac substrate utilization and whether this role is lost during heart failure. The first specific aim is to determine whether NO controls cardiac FFA and carbohydrate metabolism. The rate of FFA and carbohydrate oxidation in the heart, before and after NOS blockade, will be measured in conscious dogs by infusing isotope-labeled FFA, glucose and lactate. Labeled substrate accumulation and the activity of key enzymes for carbohydrate and FFA oxidation will be measured in cardiac biopsies freeze-clamped at the end of the in vivo experiment. The rapid freezing of the tissue will preserve the activation state of enzymes from in vivo to in vitro. The second specific aim is to determine whether the myocardial metabolic and biochemical alterations occurring during heart failure are similar to those found after NOS blockade in normal hearts and if they can be reversed by a NO-releasing agent. The same methods in vivo and in vitro will be employed. Heart failure will be induced in dogs by chronic pacing. The third specific aim is to determine whether acute alterations of arterial substrate concentration can affect cardiac oxygen consumption during heart failure and if this effect can be reversed by NO-releasing agents. Our preliminary data indicate that FFA consumption
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can cause increased in cardiac O2 consumption unrelated to hemodynamic changes, but only when NO is absent. These studies will elucidate the role of NO in the pathophysiology of heart failure. This will also provide a new pharmacological mechanism of NO-donors in the treatment of heart failure. based on direct control by these agents on cardiac metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORONARY TO MYOCYTE SIGNALING Principal Investigator & Institution: Hintze, Thomas H.; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 31-JUL-2006 Summary: (provided by applicant) During the previous funding period we have concentrated on the hypothesis that the disappearance of NO production by the coronary circulation is important in the process of cardiac decompensation. Those aims were supported by showing that the production of NO both in vivo and in vitro essentially disappears at the time of cardiac decompensation caused by rapid ventricular pacing. In addition, we showed that the reduction in NO production was associated with a shift in substrate uptake from fatty acids to glucose and to an increase in oxygen consumption in vitro. Our previous studies indicated that the reduction in NO production during pacing induced heart failure was due to a reduction in the mRNA and protein for ecNOS. Recently it has been shown that statins increase the message half-life for NO synthase by an action on Rho kinase and that is independent of lipid lowering. We will use statins during the evolution of pacing induced heart failure to maintain NOS protein, NO production and potentially to alter the progression of heart failure in Specific Aim 1. In the human heart we have recently found that implantation of an left ventricular assist device (LVAD, to unload the LV) results in a greater production, perhaps the recovery of production, of NO at the time of transplant then in other falling human hearts. In Specific Aim 2 we will determine if the regeneration of NO production contributes to the recovery of dilated myopathy and heart failure after cessation of pacing. The discontinuation of rapid ventricular pacing after the development of heart failure results in at least partial recovery of cardiac function over time and the potential role of NO has not been previously studied. In Specific Aim 3, we will continue to study the ability of the explanted falling human heart to produce and respond to NO. We will concentrate on the difference in hearts with LVAD and examine the role of cAMP as a method to increase NO production as a compensatory mechanism. Finally in specific Aim 4, we will use mice deficient in ability to produce NO, ecNOS-/- mice, to determine the consequence of the genetic lack of NO on hemodynamics, cardiac structure, function and glucose metabolism with time. Thus, we will establish new directions 1) examining the role of NO in the therapeutic and 2) in the recovery from pacing induced heart failure. We will use 3) human hearts and 4) transgenic mice to establish relevance and determine molecular mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CROSS-MODULATION OF EXCITABILITY/CA IN HEART FAILURE Principal Investigator & Institution: O'rourke, Brian D.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: Heart failure currently affects more than two million Americans and its economic and human tool will continue to increase as the population ages. Strictly
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Heart Failure
defined, heart failure is an inability to match cardiac output to physiological demand; however, roughly half of the early deaths following diagnosis are thoroughly cataclysmic arrhythmic events, or Sudden Cardiac Death (SCD). SCD is presumed to result from a set of primary cellular alterations that predispose the failing heart to a fatal electrical event. A leading hypothesis has been that prolongation of the cardiac action potential resulting from slowed repolarization shifts the cell into a vulnerable state. Two important changes with heart failure that could influence repolarization are a reduction in repolarizing K/+ currents and a slowed rat of removal of intracellular Ca/2+. The former involves a selective reduction in the transient outward K+ current (I/to/1) and the inward rectifier K+ current (I/k1) while the latter results from a decrease in the sarcoplasmic reticulum Ca/2+ ATPase (SERCA2a) and a increase in sarcolemmal Na/+/Ca/2+ exchange in the sarcoplasmic reticulum Ca/2+ ATPase (SERCA2a) and a increase in sarcolemmal Na/+/Ca/2+ exchange (NCX). The full scope of cellular alterations in heart failure can only be understood when all of the changes are considered together; changes in the action potential waveform will govern the triggered release of Ca/2+ from the sarcoplasmic reticulum and conversely, intracellular Ca/2+ will reshape the action potential. At present, little is known about the relative importance of each of these factors on the contour of the action potential and the intracellular Ca/2+ transient in normal or failing heart cells. The goal of the present application is to examine how varying each these factors (e.g., I/to, I/k1, SERCA2a, and NCX) affects the cellular action potential and Ca/2+ transient of each change to the integrated cell response. This effort will be aided by the parallel development of a comprehensive computer model of action potentials and Ca/2+ handling. Special attention will be paid to how the alterations contribute to the susceptibility of the cardiac cell to arrhythmias. The ultimate objective is to understand which changes associated with heart failure contribute most to the pathology of the disease, so as to precisely target therapy to the site(s) that correct both the electrophysiological and mechanical alterations of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECIPHER STICH Principal Investigator & Institution: Panza, Julio A.; Medstar Research Institute Hyattsville, Md 20783 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The Dobutamine Echocardiography in Patients with Ischemic Heart failure Evaluated for Revascularization Study, as part of the Surgical Treatment for Ischemic Heart Failure Trial (DECIPHER-STICH), is designed to address the hypothesis that assessment of myocardial viability with dobutamine echocardiography (DE) in patients with coronary artery disease (CAD), left ventricular (LV) dysfunction and heart failure (HF) identifies the patients who derive the greatest survival benefit from surgical revascularization over medical therapy. In addition, this study will determine the value of DE for the prediction of recovery of LV function following revascularization, the clinical value of DE relative to that of radionuclide techniques used for the same purpose, and the relationship between abnormal LV size and shape and the contractile reserve of dysfunctional myocardium. The overall objective is to define the role of the assessment of myocardial viability with DE in the clinical evaluation and selection of the best treatment modality for this high-risk subset of patients with CAD. DECIPHER-STICH is proposed as an ancillary study to the largescale STICH trial, a multicenter international randomized study designed to define the role of coronary artery bypass grafting (CABG) and surgical ventricular restoration
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(SVR) in the treatment of HF in patients with CAD and LV dysfunction. In previous studies, DE has compared favorably to other methods for the detection of viable Myocardium. The widespread availability of echocardiography and the possibility of simultaneously deriving information about structural abnormalities (e.g., thrombi), valve function, and intracardiac pressures in addition to the real-time assessment of regional and global systolic function make DE particularly useful for the comprehensive evaluation of CAD patients with LV dysfunction. Because patients in the STICH trial will also undergo radionuclide tests, the DECIPHER-STICH study will allow a comparison of the most commonly used techniques for assessment of myocardial viability. Patients recruited into the STICH trial will be invited to participate in the DECIPHER-STICH study and asked to sign a separate consent form prior to the randomized assignment of therapy. Forty centers from North America and Europe recruiting patients into the STICH trial have agreed to take part in the DECIPHERSTICH study. A total of 1,450 of the 2,800 patients enrolled into the STICH trial will undergo DE prior to treatment. DECIPHER-STICH will address the hypothesis of greater beneficial effect of CABG over medical therapy alone on 3-year survival rate with 80% power to detect a 25%-to-12.5% reduction in all-cause mortality in patients with viable myocardium. In addition, the study will have >99% power to address three important secondary hypotheses. The results of this study will provide definitive information regarding the value of assessing myocardial viability with DE and significant clinical implications for the selection of patients with CAD, LV dysfunction, and HF who are most likely to benefit from surgical revascularization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DECISION MAKING IN END-STAGE HEART FAILURE Principal Investigator & Institution: Hauptman, Paul J.; Internal Medicine; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2007 Summary: (provided by investigator): The investigator, Paul J. Hauptman MD, proposes a program of research focused on congestive heart failure in its advanced stages. This is a disease of increasing prevalence, especially in the elderly, accounting for high morbidity and mortality. However, little is known about actual and self-reported practice. The research program is in two complementary parts. The first is designed to examine the use of chronic continuous outpatient intravenous infusions of inotropic drugs, a therapy associated with high costs, unproven clinical efficacy and the potential to shorten survival while achieving palliation. The investigator will use administrative and clinical data from several Medicare databases including the records of a Durable Medical Equipment carrier encompassing a 17-state region and Medicare Provider Analysis and Review (MedPAR), Carrier, Denominator and Hospice Analytical Files for the period 1997-2000. Specifically, the population of older Medicare beneficiaries receiving, and the physicians prescribing, this therapy will be described and contrasted with the demographics and outcomes of older patients hospitalized for heart failure but not receiving the drugs. The data will be used to develop predictors of inotropic agent use and mortality in this group at risk for re-admission and death. The second part is designed to assess physicians' knowledge about, attitudes toward and practices regarding the care of end-stage heart failure patients including perceptions of patient prognosis, quality of life, efficacy/toxicities of inotropic drugs and the role for hospice in a survey of 1200 cardiologists, geriatricians, internists and family/general practitioners. Approximately one-third of the physicians will be known prescribers of inotropic drugs. We plan to investigate how physicians make decisions and the degree
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Heart Failure
to which the care an end-stage patient receives is influenced by physician specialty, volume, or other factors. Formal survey development methodology including performance of focus groups, cognitive interviews, and pilot testing will be applied. These studies will form the conceptual framework for an intervention study designed to address, at physician and patient levels, the process of selection of care options for older heart failure patients near the end of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION AND DISABILITY IN PATIENTS WITH HEART FAILURE Principal Investigator & Institution: Turvey, Carolyn L.; Psychiatry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Description (adapted from investigator's abstract): In this application for a Mentored Research Scientist Development Award, Carolyn L. Turvey will obtain expertise in the relation between physical disability and depression in late-life. Dr. Turvey will study the relationship between physical disability and depression in elder patients with congestive heart failure (CHF). Heart failure is a major source of disability in the elderly because patients experience fatigue and breathlessness when performing even minor activities of daily living. Accordingly, there are high rates of depression in heart failure patients, ranging from 17-26 percent. Disability is strongly associated with depression for this group. Dr. Turvey aims to identify how patients with CHF can cope successfully with their illness and with physical disability. She will compare CHF patients with and without depression on their level of disability, how they cope with the illness and disability, and the degree and quality of social support they receive. She will then determine which of these factors predicts time to remission of a depressive episode. She will use the information gathered in this study to develop interventions designed to reduce depression in CHF patients. She will develop a brief intervention that teaches CHF patients cognitive and behavioral skills for coping with their illness and the most effective ways of engaging social support. Dr. Turvey proposes a training and research program making use of the diverse resources at the University of Iowa - the Departments of Psychiatry, Psychology, Epidemiology and the Aging Studies Program. Dr. Turvey seeks training in gerontology and the design and implementation of outcomes research. As part of this training, she has arranged visits to other sites that specialize in the treatment of late-life depression and the relation between depression and disability in the elderly. Her long-term career goal is to develop interventions that promote healthy aging amongst elders faced with functional decline. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION AND CARDIOVASCULAR PATHOLOGY
HEART
FAILURE
ASSOCIATED
Principal Investigator & Institution: Johnson, Alan K.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 21-JAN-2003; Project End 31-DEC-2007 Summary: Depression is both a debilitating psychological disorder and a condition that affects an individual's physical well-being. Depression is a recognized risk factor for heart disease. Research has demonstrated that depression predisposes an individual to myocardial infarction, sudden death, atherosclerosis, thrombosis and arrhythmias. While the behavioral and cognitive aspects of depression have been studied extensively,
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there has been much less research investigating the mechanisms responsible for the physiological consequences of mood disorders. Exposure of rodents to a series of chronic mild stressors (CMS) generates key behavioral characteristics of human depression that are observable and quantifiable. The CMS model of experimentallyinduced depression (ID) mimics the reduced responsiveness to pleasurable stimuli (anhedonia)which is a pivotal diagnostic criterion seen in depression. In the CMSdD model, anhedonia is induced by presenting mild unpredictable stressors (e.g., paired housing, stroboscopic illumination, white noise) of varying durations. In rats,anhedonia is operationally defined as a decrease in responding for a previously demonstrated reinforcer (reward). Recently, we have begun to characterize cardiovascular function in rats with CMS-ID. We have found that rats exposed to CMS for 4 weeks showed anhedonia along with cardiovascular alterations. Similar to patients with depression and with heart failure,CMSgD rats had elevated resting heart rates and reduced heart rate variability. In addition, rats exposed to CMS have increased susceptibility to experimentally-induced premature ventricular contractions. In other studies investigating the behavioral consequences of heart failure, we have found evidence of anhedonia (i.e., experimental depression) in rats with experimental myocardial infarction. The proposed research program will extend our characterization of the cardiovascular changes that accompany experimentally-induced depression and investigate the role of brain serotonergic mechanisms that are hypothesized to be common in the mediation of cardiovascular alterations that accompany both experimental depression and experimental heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DUAL GENE THERAPY FOR HEART FAILURE Principal Investigator & Institution: Nuss, H B.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JAN-2002 Summary: Heart failure is a multifactorial disease, having both electrical and contractile components. Downregulation of key potassium channels and concomitant prolongation and instability of repolarization, predispose the heart to arrhythmias. Meanwhile, downregulation of the sarcoplasmic reticulurn Ca2+ ATPase and concomitant calcium handling abnormalities contribute to depressed myocardial contractility. The electrical abnormalities and the contractile abnormalities are not mutually exclusive. Alterations in the control of membrane voltage will modulate the triggered release of Ca2+ from the sarcoplasmic reticulurn and, conversely, alterations in the intracellular calcium transient will influence membrane potential. It is the interplay between the electrical and contractile abnormalities of heart failure which compounds the complexity of abnormalities and confounds the design of successful treatments. Novel antiarrhythmic gene therapy based upon manipulation of a select K channel gene alone to decrease susceptibility to arrhythmias may lead to depressed contractility, which is already depressed in heart failure. Conversely, genetic manipulation of a SR Ca2+ ATPase protein alone, to amplify contractility, may create a proarrhythmic substrate in a failing heart which is already predisposed to fatal arrhythmic events. Thus, monogenic strategies, based upon selective overexpression of a single gene, may not suffice to correct heart failure abnormalities because of the interplay between excitation and contraction in cardiac muscle. This proposal seeks to offset abnormalities of tachycardia, pacing- induced heart failure in rabbits using combination gene therapy: overexpression of a select K channel gene and a SR Ca2+ ATPase gene in tandem. As a prelude we will test the hypotheses that gene therapy targeted to correct the electrical
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Heart Failure
abnormalities alone or the calcium handling abnormalities alone will result in adverse conditions. The proposal focuses on potassium channels and SR Ca2+ ATPase's that are highly relevant to repolarization and contractility in the human heart failure. In vivo adenoviral mediated gene transfer, cellular and cardiac electrophysiology, and quantitative modeling will be used to investigate repolarization and calcium handling with the goal of correcting the electrical and contractile abnormalities in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENDOTHELIUM AND VASCULAR FUNCTION Principal Investigator & Institution: Kaley, Gabor; Chairman; Physiology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 31-JUL-2006 Summary: (Applicant's abstract) This Program Project Grant renewal application describes studies we plan to perform as a continuation of our project on the role of vascular endothelial cells in the regulation of cardiovascular function in a variety of physiological and pathophysiological states. The project leaders represent related research disciplines, each of which will contribute to the collaborative efforts of the investigators. The common theme of the projects is the multifaceted role of the interaction among the locally released, endothelium-derived mediators, -primarily nitric oxide (NO), and oxygen free radical species -in the regulation of vascular smooth muscle functions, and parenchymal cell metabolism in heart and skeletal muscle of mice, dogs, bovine and humans. The participating investigators have been in the forefront of research in this area and it is anticipated that, as a result of the coordinated program proposed, the role of endothelial mediators in blood vessel biology as well as their possible role in the changes evoked by aging and disease states, such as heart failure, will become clearer. The overall goal of the program is to test the hypothesis that a reduction in endothelial NO synthesis and/or bioavalaibility is the dominant pathogenetic factor in the alterations of vascular and myocyte function, and cell death, as a consequence of the heart failure and aging. We plan to gain further mechanistic insight into the role of NO in these processes and to evaluate the beneficial effects of interventions directed towards the correction fo the NO deficiency by a variety of methods to reverse the aging - and heart failure - related deterioration of cellular function. Project 2 will study interactions between reactive O2 and NO-derived species in the control of signaling systems that affect coronary vessel contractile function. Project 5 will examine the pathophysiologic relevance of the reduction and restoration fo NO production on the development of heart failure. Project 6 will investigate whether the progressive increase in oxidative stress, and myocyte and cell death are characteristic of cardiac decompensation and aging. Project 4 will have as its goal to attempt to reverse vascular aging in mice by a variety of methods to reestablish control of microvascular function by NO. The Administrative Core will support the research projects. The Molecular Biology Core will coordinate all work related to the transgenic mouse colony, including the characterization of the aging vascular phenotype. Though these multidisciplinary approaches we will gain a better understanding of the causes of decompensated heart failure and the vascular consequences of aging as they relate to the synthesis and activity of endothelium - derived NO, and the attenuation or reversal of the sequelae of these conditions by enhancing the bioavailability of NO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FREE RADICALS AND MUSCLE DYSFUNCTION IN HEART FAILURE Principal Investigator & Institution: Supinski, Gerald S.; Professor; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: Recent work indicates that the intrinsic force-generating capacity and metabolic function of skeletal muscles are altered in patients with heart failure, and that skeletal muscle dysfunction contributes to fatigue and breathlessness in these patients. The underlying mechanism by which these myopathic changes occur in heart failure, however, is currently unknown. The purpose of the studies in this proposal is to test the hypothesis that some or all of the myopathic changes that develop in this condition are due to excessive myocyte generation of free radicals. We postulate that heart failure elicits an increase in myocyte phospholipase A2 (PLA2) activity levels, and that arachidonic acid generated by PLA2 interacts with the electron transport chain to augment free radical formation in resting and contracting muscle. We further propose that the radicals so produced react with and modify protein and lipid components of muscle which, in turn, alters muscle force generation and fatiguability. These hypotheses will be tested in three groups of experiments; in all studies a coronary ligation model will be used to produce heart failure in rats. The purpose of Objective I studies is to find evidence of heightened free radical formation by skeletal muscle in heart failure; experiments will measure both indices of free radical reaction with cellular constituents (i.e. lipid and protein oxidation products) and directly measure free radical formation by muscle using novel fluorescent techniques. Objective II studies will determine the cellular pathways responsible for free radical generation by skeletal myocytes in heart failure and, more specifically, determine if and by what process phospholipase A2 modulates muscle free radical generation in this condition. In Objective III, we will examine the role of free radicals in inducing muscle weakness and excessive fatiguability by determining if administration of free radical scavengers to heart failure animals preserves normal muscle function. Our preliminary studies provide the first evidence that excessive skeletal muscle free radical generation in heart failure is linked to reductions in muscle force-generating capacity in this condition. These data suggest that the proposed experiments should provide important information regarding the pathogenesis of heart failure-related skeletal muscle dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENES DIFFERENTIALLY EXPRESSED DURING HEART FAILURE Principal Investigator & Institution: Gwathmey, Judith K.; Professor of Medicine and Physiology; Gwathmey, Inc. 763 E Concord Ave Cambridge, Ma 02138 Timing: Fiscal Year 2003; Project Start 01-APR-2001; Project End 31-AUG-2005 Summary: (provided by applicant): The American Heart Association estimated the cost of cardiovascular disease in the United States in 2000 to be at $326.6 billion. This figure includes health expenditures and lost productivity resulting from morbidity and mortality. Heart failure is not a disease of the elderly or persons who live unhealthy lifestyles. The highest incidence occurs between 25-45 years of age. Although more patients are surviving their first myocardial infarction, they go on to develop progressive left ventricular dysfunction and end-stage heart failure. As a result, the incidence of congestive heart failure is increasing. Changes in gene expression profiles between normal tissue and diseased tissue can lead to identification of novel drug
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Heart Failure
targets and to the development of drugs that will be able to interfere with disease development. Our hypothesis is that altered gene expression is the basis of the structural and functional changes that accompany the development of heart disease and that changes in gene expression profiles are important indicators of specific disease stages of heart failure. We predict that changes in the expression profile of a critical set of genes will be important indicators and diagnostic markers of heart disease. We have found that about 30 percent of the genes identified in our differential screening have no informative similarity to known genes in any of the public databases. These genes are excellent candidates as drug targets and/or as possible diagnostic markers. Our specific aims are 1) To fully characterize selected genes based on their differential expression in heart failure; 2) To validate the potential targets identified in Phase 1 and prioritize these gene targets; 3) To determine if the levels of the corresponding gene products (proteins) have changed in a manner similar to the change in RNA levels; 4) To link information on the differences in gene expression and protein levels with consequences in cardiac myocytes and muscle strips by using adenoviral vectors to infect myocytes with transgenes that are over-expressed or knocked down (i.e., antisense); 5) To determine if changes in the gene expression pattern that we have identified in the turkey model are also present in the hearts of human patients with end-stage heart failure; 6) To produce the first "human heart failure chip"; 7) To patent novel therapeutic targets that have been identified and validated Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC DETERMINANTS OF HYPERTENSION, LVH, AND CHF Principal Investigator & Institution: Dries, Daniel L.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 17-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The endogenous cardiac hormonal system (CHS) moderates blood pressure, the development of left-ventricular hypertrophy (LVH) in response to hypertension, and delays progression of systolic heart failure. The "afferentlimb" of the CHS refers to the ability of the myocardium to release atrial and brain natriuretic peptide (ANP and BNP) in response to pressure overload, and the "efferentlimb" describes the biological action of these hormones in target tissue. Plasma levels of cGMP are tightly correlated with the efferent actions of the cardiac hormones providing a validated method to measure the efferent function of the CHS in humans. We hypothesize that gene-environment interactions involving genes related to critical components of the afferent and efferent cardiac hormonal signaling pathways, and gene-gene interactions between these genotypes and the ACE-gene, contribute to interindividual variation in susceptibility to hypertensive heart disease. Moreover, differences in the frequencies of these alleles in special populations may explain the increased susceptibility of African-Americans to LVH, development of heart failure, and progression of established heart failure. In order to address these hypotheses, we will identify patients with untreated hypertension and LVH in a random population sample of approx. 3,000 subjects. We will then compare the afferent and efferent function of the CHS in African- American and Caucasian subjects with untreated hypertension and leftventricular hypertrophy, and identify phenotypes characterized by reduced function of either the afferent or efferent function of the CHS. We will sequence these subjects to identify sequence variants in candidate genes critical to the cardiac hormonal signaling pathways (the gene for ANP, BNP, the type A and C cardiac hormone receptors, and corin). We will then study the association of these genotypes with prevalent hypertension, cardiac MRIdetermined LVH, and prevalent hypertensive
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cardiomyopathy in the two ethnic cohorts. In addition we will analyze the association of these genotypes with prognosis in patients with advanced systolic heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GI CARDIOPROTECTION
SIGNALING
IN
CARDIOMYOPATHY
AND
Principal Investigator & Institution: Baker, Anthony J.; Associate Professor; Northern California Institute Res & Educ 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: GROUP TREATMENT FOR DEPRESSION IN HEART FAILURE Principal Investigator & Institution: Friedman, Michael A.; Psychology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 14-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): The overall aim of this research is to develop an efficacious group psychotherapy for the treatment of major depression among individuals with congestive heart failure. Both major depression and heart failure are associated with severe loss of functioning and increased mortality, and this co-morbid
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Heart Failure
condition is particularly debilitating. While treating depression among heart failure patients has the potential to improve functioning and prolong life in this population, there are currently no empirically-supported treatments for depression among heart failure patients. Among the several well-validated psychosocial treatments, group cognitive-behavioral therapy (CBT) has been proposed as efficacious, and has established feasibility among heart failure patients. Group CBT may be particularly efficacious among CHF patients with depression due to the potential for increasing patient social support. Initial research suggests that there are several ways in which current group CBT could be improved to treat major depression among CHF patients, including: (1) the use of an "open" group format that allows for immediate patient care, (2) integration of individual interventions to individually tailor treatment goals and improve adherence to treatment, and (3) family-based interventions within the group CBT format to mobilize patient social support. The proposed integrated cognitivebehavioral therapy program includes group, individual, and family treatment (GIFT) for depression among individuals with CHF (GIFT-CHF). The current proposal is designed to develop the GIFT-CHF program. The proposal consists of three phases: a Development, Pilot, and Revision Phase. During the Development phase of the GIFTCHF, the goal of the research will be to: (a) develop an integrative group therapy program for depressed patients with heart failure (GIFT-CHF); (b) develop a therapist training program; and (c) develop and test the reliability and validity of competence and adherence rating scales. During the Pilot phase of the GIFT-CHF program, the goal will be to conduct a small pilot trial investigating the short-term efficacy of the GIFT-CHF program in comparison to a Standard Medical Care/Wait-List control group, and determine effect size. Finally, during the Revision phase of the GIFT-CHF program, the goal of the research will be based on the results of the Development and Pilot phases, to revise the GIFT-CHF program and treatment manual. This treatment development grant will lay the groundwork for a large-scale treatment outcome study of the GIFT-CHF program for depressed individuals with congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEART FAILURE & NORMAL SYSTOLIC FUNCTION IN OLDER ADULTS Principal Investigator & Institution: Masoudi, Frederick A.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: Dr. Masoudi will complete his fellowship in cardiology in June 2000, and will join the faculty as an assistant professor of Medicine in the Divisions of Cardiology and Geriatric Medicine at the University of Colorado Health Sciences Center. He has completed the course requirements for the M.S.P.H. degree at the University of Colorado and has been involved with the National Hearth Failure (NHF) Project, a program sponsored by the Health Care Financing Administration to measure and improve the care of Medicare beneficiaries with heart failure. The applicant's long- term goals are to develop a career as an independent investigator in cardiovascular diseases in the older population in an academic setting. His immediate goals are to study patients from the NHF database with heart failure and preserved left ventricular systolic function (LVSF); obtain additional methodological expertise with formal course work; participate in related research in cardiovascular disease in older persons; and participate in clinical cardiology at Denver Health Medical Center. The Environment: Dr. Masoudi's research office will be in Center on Aging Research Section, which houses more than 15 health services researchers dedicated to the study of health care quality
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and outcomes in the older population. His research mentor is Andrew Kramer, MD, Professor of Geriatric Medicine and Director of the Center on Aging Research Section at the University of Colorado. He will work closely with geriatricians, research methodologists, cardiologists, and his co-sponsors, who are leaders on the NHF Project. The Research: Heart failure with preserved LVSF is reportedly common in the older population. In spite of its high prevalence, relatively little is known about the characteristics of these patients or their health outcomes. The objectives of the proposed research are to describe the population of older Medicare beneficiaries hospitalized across the United States with heart failure and preserved LVSF; identify the determinants of mortality and hospital readmission in this population; and compare risk-adjusted rates of mortality and hospital readmission in this population with those of patients with heart failure and impaired LSVF. To accomplish these aims, we will analyze detailed clinical information from the hospital charts of more than 20,000 patients collected as part of the NHF Project linked to the administrative data sets containing patient-level information. The results of this research will better characterize these patients, will explore the important determinants of patient outcomes, and may provide insights in the development of interventions targeted specifically at this population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEART FAILURE AND BETA-BLOCKER USE IN OLDER ADULTS Principal Investigator & Institution: Ahmed, Ali; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The purpose of this revised NIA K23 award application (1 K23 AG19211-01A1) is to provide the candidate, Ali Ahmed, MD, MPH, a fellowship trained geriatrician with additional training and research experience that will enable him to become an independent investigator in geriatric outcomes research with a special focus on heart failure. Dr. Ahmed has conducted secondary analyses of an Alabama Quality Assurance Foundation (AQAF) database (N =1,000) to study correlates and outcomes of ACE inhibitors in older adults with heart failure. These studies have resulted in fifteen first-authored manuscripts (one published, nine in press/accepted, three under review and two in preparation) over the last four years. In this current application, he proposes to build upon his previous experience in health services and epidemiological research to conduct a series of analyses of a much larger database derived from the CMS-funded Alabama Heart Failure Project (N = 10,000), reflecting heart failure cases discharged between 1998 and 2001. His research will permit him to define correlates of beta-blocker use and the association between beta-blocker use and one-year mortality and hospitalization in older adults with heart failure. The candidate will learn and use advanced outcomes research methodologies such as multivariate models for risk adjustment, including propensity scores and instrumental variables. He also proposes to conduct a pilot intervention study during the last three years of the award period to increase the use of ACE inhibitor and beta-blockers in older adults with heart failure. He plans to use the results and the experience of these studies to apply for an R01 research grant during the last two years of the award period. In addition, he will also develop plans for a pilot study in collaboration with Louis Dell'Italia, MD (UAB Cardiology and Physiology) to provide mechanistic insight into one of the important findings of the above studies. Dr. Ahmed proposes a career development plan that includes coursework and fieldwork at the University of Alabama at Birmingham (UAB) and at the AQAF. His primary sponsor Richard M. AIIman, MD (UAB Geriatrics) and
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co-sponsors Louis Dell'Italia, MD and Catarina Kiefe, PhD, MD (UAB Preventive Medicine and Biostatistics), in collaboration with a team of other senior UAB and external faculty will supervise his training and research activities. A graduate of the NIA Summer Institute on Aging Research and NIH K30 Clinical Research Training Program, his long-term goal is to attain independence as an investigator in the field of patientoriented heart failure outcomes research in older adults and study various factors associated with outcomes in older adults with heart failure and to design appropriate interventions to improve outcomes. The proposed training and research will provide him the necessary skills and experience to advance his career to the next phase, in becoming an independent investigator in outcomes research involving heart failure in older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IONIC CURRENTS AND AUTONOMIC REGULATION IN HEART FAILURE Principal Investigator & Institution: Yatani, Atsuko; Professor; Medicine; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Cardiac hypertrophy is an initial adaptive process in response to a variety of physiological and pathological stimuli. In certain conditions such as chronic hypertension, compensated hypertrophy an lead to congestive heart failure. Previous studies have proposed that abnormal excitation contraction coupling and regulation may be responsible for impaired contractility in failing heart. A number of Ca/2+ handling systems involved in myocardial contraction and the cellular basis for the defect in heart failure is not completely understood. In addition, the correlation between the functional abnormalities and the stages of hypertrophy, including before and during the onset of heart failure, as well as end stage congestive heart failure, has not been well- characterized. Our long term objective is to understand the cellular mechanisms that rigger cardiac hypertrophy and regulate the transition between compensated and decompensated phases of cardiac hypertrophy. This application focuses on cellular mechanisms important for myocardial Ca/2+ homeostasis. We hypothesize that changes in ionic currents and autonomic regulation that are involved in cellular Ca/2+ homeostasis occur in hypertrophied myocardium and that the degree of alteration is dependent upon the severity of hypertrophy and the presence of heart failure. To test this hypothesis, a transgenic mouse model of compensated hypertrophy which exhibits cardiac physiological events observed in animal models and human heart failure with a remarkable recapitulation with biochemical alterations associated with various stages of disease will be determined by patch clamp technique. Once the failure by transferring gene of certain defective components. This research is fundamental to our understanding of cellular mechanisms of cardiac hypertrophy and failure. These studies will not only field significant new information on the basic cellular mechanisms that regulate heart failure, but will also provide new and valuable insights into the design of drugs as well as novel therapeutic approaches for cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ISCHEMIC TOLERANCE IN HYPERTROPHIED MYOCARDIUM Principal Investigator & Institution: Butler, Karyn L.; Assistant Professor; Surgery; Morehouse School of Medicine Atlanta, Ga 30310
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Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Cardiac chamber remodeling following myocardial infarction or in response to hypertension, may lead to left ventricular hypertrophy and cardiac failure. Preconditioning, or ischemic adaptation, represent the intrinsic capacity of the heart to protect itself from ischemic injury. The molecular of this phenomenon remains to be further characterized. Clinical and experimental indicate that hypertrophied hearts are more vulnerable to ischemic insult compared to non-hypertrophied hearts. In nonhypertrophied myocardium, cardiac preconditioning can attenuate ischemia/reperfusion induced contractile dysfunction via G-protein coupled receptor signaling. Our preliminary data suggest that compensated hypertrophied hearts exhibit enhanced ischemic tolerance after preconditioning compared to non-hypertrophied hearts. This provocative observation suggests that the signaling pathways involved in adaptive hypertrophy may enhance ischemic tolerance. Moreover, we have observed that this relative preservation of ischemic adaptation in the hypertrophied heart is lost in a time-dependent manner as the heart transitions from compensated hypertrophy to cardiac failure. The purpose of this project is to define the molecular pathways of ischemic adaptations in hypertrophied myocardium. It is anticipated that these new mechanistic insights will advanced our understanding of ischemic/reperfusion injury and begin to identify therapeutic targets that may improve myocardial function following ischemic injury in the hypertrophied heart. Ischemic heart disease accounts for more than 600,000 deaths annually in the United States. Recent advances in the medical management of acute coronary syndromes and cardioprotective strategies used during coronary revascularization have increased patient survival after acute myocardial infarction. Despite this progress, complications may result as the necrotic myocardium heals and patients may go on to develop LVH and congestive heart failure. The mechanisms involved in the transition from compensated hypertrophy to heart failure are complex. Overall, these studies will be the first to definitively establish the role of the G- protein-coupled alpha-adrenergic pathway as a critical determinant of preconditioning in hypertrophied hearts. Defining the mechanisms of ischemic tolerance of hypertrophied myocardium may lead to enhanced cardioprotective strategies that will minimize ischemic injury in patients with hypertension and left ventricular hypertrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: JAK-STAT SIGNALING IN HUMAN HEART FAILURE Principal Investigator & Institution: Moravec, Christine S.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Heart failure remains the leading cause of death in the United States. It is impossible to develop a truly successful therapeutic strategy for patients with heart failure until we have a better understanding of the cellular and molecular events which are involved in the transition from stable, compensated cardiac hypertrophy to the downward spiral of heart failure. Several candidate pathways have been shown to mediate the compensated hypertrophy phase of cardiac remodeling. Among these is the JAK-STAT pathway, which is present in cardiac myocytes, is activated during hypertrophy, and can be shown to be stimulated in the heart by members of the IL6 cytokine family, as well as endothelin, angiotensin II, and mechanical stretch, all of which are potent stimuli during the transition to cardiac failure. Although studies in animal models have suggested that the JAK-STAT pathway may be involved in the compensated hypertrophy phase of cardiac remodeling,
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activation of the pathway has never been measured in an animal model of heart failure, or in the human failing heart. Preliminary data from our laboratory suggest that the JAK-STAT pathway is activated in the end-stage failing human heart, that it may be stimulated by angiotensin II, and that activation can be reversed when the failing human heart is mechanically unloaded. The presence of STAT dimers in the nuclei of failing human hearts suggests a role for this pathway in the altered transcriptional regulation associated with end-stage heart failure. We therefore hypothesize that angiotensin II-mediated activation of the JAK-STAT pathway is responsible for changes in cardiac muscle function and gene expression which occur in the transition from compensated hypertrophy to failure in the human heart, and that this pathway is inactivated during mechanical support of the failing human heart, leading to the "reverse remodeling" which has been observed by our laboratory and others. We will test this hypothesis using a combination of human heart tissue studies and a mouse model of the transition from compensated left ventricular hypertrophy to heart failure. In the nonfailing human heart, the human heart with compensated left ventricular hypertrophy, the failing human heart, and the failing human heart which has been subjected to mechanical hemodynamic support, we will measure activation of the JAKSTAT pathway, markers of the heart failure phenotype, and the role of angiotensin II in mediating activation. In paired samples of tissue before and after mechanical unloading, we will use oligonucleotide microarray technology to identify genes which are regulated by unloading and which are potentially responsive to regulation by STAT transcription factors. In the mouse model of aortic banding, we will assess the changes in cardiac function and gene expression during the transition from hypertrophy to failure, define the relationship between these alterations and activation of the JAK-STAT pathway, and assess the role of angiotensin II in mediating the transition phase. This study will allow us to define the role and the timecourse of angiotensin II-mediated activation of the JAK-STAT pathway in human cardiac hypertrophy and heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIMB CONGESTION AND EXERCISE REFLEXES IN HEART FAILURE Principal Investigator & Institution: Sinoway, Lawrence I.; Professor of Medicine; Medicine; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-DEC-2003 Summary: (Applicant's abstract): The long-range goals of the PI are to evaluate the mechanisms that regulate blood flow delivery in heart failure. The short-range goals are to determine: 1) the interstitial metabolites that may evoke the muscle metaboreflex in heart failure, and 2) the effects of exercise conditioning on reflex responses to exercise in heart failure. Recent work from our laboratory has suggested that the muscle metaboreflex is engaged at low levels of rhythmic forearm exercise in heart failure patients. This premature reflex engagement was associated with increased sympathetic drive directed to inactive skeletal muscle. To date no one has characterized the interstitial concentrations of the many muscle metabolites that may be responsible for engaging this reflex in normal subjects and those with heart failure. We have begun using the microdialysis method to directly determine interstitial concentrations of multiple potential metaboreceptor stimulants in humans. We have spent a great deal of effort over the last few years modifying microdialysis methods so that we can now measure lactate, phosphate, adenosine, potassium and hydrogen ion in the interstitium of resting and exercising skeletal muscle. In this proposal we will utilize this method
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during rhythmic quadriceps contractions in subjects with heart failure and in agedmatched and young controls as we simultaneously measure opposite leg muscle sympathetic nerve activity (MSNA). We hypothesize that K+ and phosphate will correlate best with MSNA. We will then examine the effects of quadriceps muscle conditioning on muscle metaboreflex activity. In separate studies, we will compare the effects of ischemic and non- ischemic conditioning on the muscle reflex in the three subject groups discussed above. We speculate that conditioning will increase limb blood flow, reduce metabolite production and in the process reduce MSNA responses to quadriceps contractions more in heart failure subjects than in controls. We speculate that ischemic forearm training will serve as a potent stimulus to attenuate MSNA in the peroneal nerve and vasoconstrictor influences in the exercising forearm. Novel components of the work described include the use of multiple state of the art human investigative techniques including microdialysis, peroneal nerve recordings of sympathetic traffic, Doppler flow measurements, 31P NMR spectroscopy, and the use of ischemic and non-ischemic exercise conditioning paradigms. To our knowledge studies such as these have not been previously performed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MATRIX METALLOPROTEINASE-2 & PROGRESSIVE CARDIAC FIBROSI Principal Investigator & Institution: Lovett, David H.; Professor; Northern California Institute Res & Educ San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Persistent dysfunctional remodeling of the heart as a response to injury represents a final common pathway resulting in ventricular failure and death. Changes in the proliferative capacity and extracellular matrix synthetic profile of the cardiac fibroblast component of the heart are primarily responsible for these events. These changes in the cardiac fibroblast phenotype are driven by conditions and peptide factors commonly present within the failing heart, including tissue hypoxia and enhanced release of pro-fibrotic peptides, such as angiotensin II, endothelin-1 and Interleukin-1. Ventricular remodeling is also associated with enhanced synthesis of several matrix metalloproteinases, of which MMP-2 (gelatinase A) may be of central importance. The primary hypothesis of this proposal is that enhanced synthesis of gelatinase A in response to ischemic injury and pro-fibrotic peptides directly drives the dysfunctional changes in cardiac fibroblast phenotypes responsible for progressive cardiac failure. This proposal will examine the transcriptional regulation of gelatinase A in response to angiotensin II, endothelin-1 and Interleukin-1 to define critical enhancer elements and transcription factors that drive high level synthesis of this enzyme in the heart. The validity of these transcriptional regulatory mechanisms will be directly tested in a genomic context using transgenic gelatinase A mice containing defined mutations in specific enhancer elements. Finally, the ability of gelatinase A as an individual agent to induce dysfunctional ventricular remodeling will be tested in vivo using targeted gene expression in the heart. These studies should provide key insights into the role of a specific matrix metalloproteinase in the cardiac response to injury and could provide the pathophysiologic basis for the development of new forms of therapy for this disabling condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MCIP1-AUGMENTING DRUGS AS NEW HEART FAILURE THERAPEUTICS Principal Investigator & Institution: Bush, Erik W.; Myogen, Inc. 7575 W 103Rd Ave, #212 Westminster, Co 800214014 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Heart failure, the common endpoint of many cardiovascular diseases, affects 700,000 individuals yearly in the United States with an annual cost of $10-40 billion. The expanding number of those afflicted with chronic heart failure and its persistently poor prognosis make it clear that additional novel treatment approaches are necessary. Progressive maladaptive cardiac hypertrophy is a key mechanism that significantly contributes to the deterioration of the failing human heart. The calcium-dependent phosphatase calcineurin (CN) plays a central role in hypertrophic signaling, being both necessary and sufficient for cardiac hypertrophy in vivo. Myocyte-enriched Calcineurin-lnteracting Protein-1 (MCIP1), a newly described CN inhibitory protein preferentially expressed in striated muscle, has recently been demonstrated to inhibit cardiac hypertrophy in response to genetic, pathologic and pharmacologic stimuli. We therefore hypothesize that small molecules which increase expression of endogenous MCIP1 protein may attenuate cardiac hypertrophy via tissueselective inhibition of CN. Myogen has developed a high-throughput whole-cell immunoassay capable of reporting endogenous MCIP1 protein expression in primary cardiomyocytes. This Phase I proposal seeks to assess the feasibility of whether this high-throughput assay can identify lead compounds that increase MCIP1 protein expression and inhibit cardiomyocyte hypertrophy in vitro. If Phase I efforts are successful, Phase II will involve expanded screening, lead compound optimization and in vivo studies to assess the ability of lead compounds to attenuate and possibly reverse cardiac hypertrophy and subsequent failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 92093 Timing: Fiscal Year 2001; 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
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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 •
Project Title: MECHANISMS OF CARDIOPROTECTION IN ISCHEMIA AND FAILURE Principal Investigator & Institution: Karliner, Joel S.; Professor of Medicine; Northern California Institute Res & Educ San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This research program involves three interrelated and interacting projects that will use novel approaches to elucidate regulatory mechanisms in acute myocardial ischemia, injury, repair, and heart failure that have relevance to human cardiac disease. The overall proposal will make extensive use of transgenic and gene targeted deletion models in mice. Methods will include biochemical and molecular approaches in isolated submitochondrial particles and intact mitochondria; biochemical and molecular studies in cell culture; biophysical studies in isolated cells and myocardial strips; hemodynamic investigations in isolated hearts; and serial hemodynamic and echocardiographic studies in living animals. All of the required techniques are currently in use in the laboratories of the responsible investigators. Cellular and molecular processes not previously investigated in the heart will be targeted. The first overall goal is to learn about how the lysophospholipid mediators sphingosine I -phosphate and lysophosphatidic acid and the actin regulatory protein gelsolin regulate myocardial responses to acute oxidative stress, injury, and remodeling. The second aim is to study the molecular regulation of matrix metalloproteinase-2 (gelatinase A) in cardiac fibroblast proliferation, extracellular matrix formation, and cardiac remodeling. The third aim is to learn how calcium responsiveness is regulated in models of acute myocardial ischernia and reversible congestive heart failure. These projects will rely on three Core Units: a hemodynamics core, a cell culture core, and a transgenic mouse core. Each of the projects will have extensive interactions with the other projects and with the core units. This proposal brings together the skills of a diverse group of investigators united by an interest in understanding mechanisms underlying the heart's response to oxidative stress. The proposed studies are novel and feasible, and are designed to lead to new approaches for the prevention of myocardial damage during acute and chronic oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MINIATURE MAGLEV VAD FOR CHILDREN & ADULTS Principal Investigator & Institution: Dasse, Kurt A.; Levitronix, Llc 85 First Ave Waltham, Ma 02451 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004
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Summary: (provided by applicant): The prevalence of congestive heart failure in the United States is nearly 5 million patients, with more than 500,000 new cases diagnosed per year. Of these patients, approximately 400,000 have a life expectancy of less than one year, and 200,000 die each year despite maximal medical therapy. To address the need for mechanical circulatory support in these patients, various left ventricular assist systems have been developed. Yet broad utilization of these devices has been limited by their size and cost. Our goal is to create a truly affordable left ventricular assist device, capable of meeting the needs of a broad range of patients with severe heart failure. The focus of this project will be to develop a miniature, low-cost, extracorporeal centrifugal left ventricular assist device, for use as a bridge-to-decision for durations ranging from days to months. Accordingly, the device will be designed to function as a bridge to recovery, transplant or an implantable device for patients in severe cardiac failure. The specific design will feature a novel magnetically levitated configuration, whose key features allow rapid acceleration and deceleration in response to prescribed motor input power cycles. The major advantages of the current design are its small and relatively simple extracorporeal design, its ability to efficiently regulate cardiac output over a large range of flow conditions, and its ease of production This program's overall goal will be to develop and optimize the design and construction of the magnetically levitated, centrifugal pump, and ascertain its physiological performance in vitro and in vivo. The specific aims of this proposal are to 1) Design and fabricate a long-term blood pump and pump controller. 2) Optimize pump design through a computational fluid dynamics model, which predicts system flow as a function of pump attributes. 3) Design and fabricate magnetically driven system controls and power supply integration. 4) Determine pressure-flow characteristics over a wide range of outputs. 5) Determine hemolysis levels over the expected range of cardiac outputs. 6) Perform preliminary in vitro endurance testing, 7) Conduct three acute in vivo experiments to demonstrate hemodynamic performance and biocompatibility. We believe that our technology, which provides effective left ventricular assistance with a small, disposable device, may provide needed benefits to the health of a broad range of patients, while not adding significantly to cost of caring for these patients. If we successfully meet the Phase I goals, we will propose in a Phase II program to refine the mechanical design with respect to manufacturing, optimize the ventricular assist control console (with appropriate safety and alarm systems), and expand the in vivo data to include longer-term animal experiments. This would provide a database to support the use of our device for longterm left ventricular support in clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS FOR ACTIVATION OF CARDIOVASCULAR SENSORY AFFERENTS Principal Investigator & Institution: Abboud, Francois M.; Edith K. Pearson Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 21-JAN-2003; Project End 31-DEC-2007 Summary: For decades, studies ofbaroreceptor activity have depended on measurements of action potentials in single fibers or whole nerve. We had no insight into the molecular components of the mechanoelectrical transducers that initiate depolarization and trigger action potentials. In fact, transduction of mechanical stimuli is one of the least understood of the vertebrate senses. Our goal has been to define the molecular basis for mechanical activation of arterial and cardiac sensory afferents. In earlier studies we defined the characteristics of aortic baroreceptor neurons (BRNs) in culture. These channels are cation-selective, non voltage-gated, and blocked by
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amiloride or gadolinium. However, their molecular identity remains unknown. A candidate family of evolutionary-conserved ion channels, the degenerin/epithelial Na+channels (DEG/ENaC), was discovered in a genetic screen for mechanosensitive genes in C. elegans. During the past 4 years we made important discoveries to advance our hypothesis that DEG/ENaC channels function as the mechanoelectrical transducer in mammalian meehanoreceptors: 1) DEG/ENaC subunits are expressed in mechanoreceptive neurons and in their sensory terminals. 2) The functions of BRNs, both in vivo and in vitro are reduced by inhibitors of DEG/ENaC channels. 3) Most important, targeted disruption of a DEG/ENaC subunit in mice reduced mechanosensation in aortic BRNs and in cutaneous mechanoreceptors but did not abolish it. We believe the mammalian mechanosensitive channels may be a heteromultimeric complex of multiple DEG/ENaC proteins, along with associated intra and extracellular "tethering" proteins. Thus, our first hypothesis is aimed at defining the subunits of the DEG/ENaC family and associated proteins that form the mechanosensitive complex in BRNs. Additionally, we have evidence that DEG/ENaC channels also play an important role in cardiac sensory neurons, not only as mechanosensors, but also as H+-sensors in the setting of myocardial ischemia. Thus, these channels could be the mediators of activation of cardiac sympathetic afferents, causing the pronounced reflex increase in sympathetic outflow in heart failure states. Therefore, our second hypothesis is aimed at defining the proton- and mechanosensitive DEG/ENaC channels of cardiac sensory afferents in dorsal root ganglia (sympathetic afferents) and nodose ganglia (vagal afferents) and determining their function under normal physiological and in myocardial ischemia and heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR VASORELAXATION
BASIS
OF
CAMP
INDUCED
CORONARY
Principal Investigator & Institution: White, Richard E.; Associate Professor; Pharmacology and Toxicology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the application): Heart failure is often the lethal consequence of a variety of cardiovascular disorders, such as myocardial infarction, hypertension, and coronary artery dysfunction. Although agents that elevate cAMP are commonly used to treat heart failure, knowledge of the cellular/molecular basis of how these drugs act is limited. The long-term goal of the proposed study is to understand how cAMP-dependent vasodilators reduce morbidity and mortality of cardiovascular disorders, and thereby suggest new approaches for the treatment of heart failure. Preliminary studies indicate that cAMP-dependent vasodilators relax coronary arteries in vitro by an endothelium-independent mechanism that involves K efflux. Subsequent patch-clamp studies suggest that cAMP opens the large-conductance, calcium- and voltage-activated potassium (BKCa) channel by stimulating the cGMP-dependent protein kinase (PKG) instead of PKA. Preliminary biochemical studies have confirmed this cross-activation. Furthermore, the effects of cAMP can be reversed by agents that inhibit the activity of phosphoprotein phosphatases. Therefore, the hypothesis of the proposed studies is that cAMP-producing agents relax coronary arteries by opening BKCa channels in coronary smooth muscle by stimulating the activity of PKG (but not PKA) and phosphoprotein phoshatase 2A (PP2A). This hypothesis will be tested by employing state-of-the-art techniques of electrophysiology and biochemistry / molecular biology to determine 1) the effect of cAMP-dependent vasodilators on
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coronary arteries in vitro; 2) the effect of cAMP-stimulating agents on whole-cell and single-channel K currents from single myocytes isolated from coronary arteries; 3) cAMP-dependent 'cross-activation' of PKG; and 4) a potential role of phosphates activity in mediating the response to cAMP in coronary arteries and whether there is a direct interaction between the BKCa channel and PP2A. It is hoped that these studies will lead to the development of novel therapeutic agents that will help reduce the morbidity and mortality associated with heart failure and other cardiovascular diseases (e.g. agents that target BKCa channels of phosphoprotein phosphatases). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF HEART FAILURE Principal Investigator & Institution: Marks, Andrew R.; Professor of Molecular Cardiology; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 30-SEP-1998; Project End 31-AUG-2007 Summary: (provided by applicant): The overall goal of this project is to elucidate molecular mechanisms that contribute to cardiac dysfunction in heart failure. This project focuses on one aspect of the disease, defects in excitation-contraction (EC) coupling. It is not the intention of the applicant to suggest that defects of EC coupling are the only mechanism underlying cardiac dysfunction in heart failure. The rationale for focusing on the role of EC coupling in heart failure is that cardiac contractility is activated by EC coupling and there is ample evidence in the literature from numerous laboratories indicating that EC coupling, and more broadly Ca2+ homeostasis, are altered in heart failure. Finally, the specific aims of this proposal focus specifically on one aspect of EC coupling, sarcoplasmic reticulum (SR) Ca2+ release which is regulated by the ryanodine receptor/Ca2+ release channel (RyR2). During the past 4 years of this project we have shown that RyR2 comprise a macromolecular complex in which PKA, PP1, PP2A are bound to the channel via targeting proteins that bind to RyR2 through leucine/isoleucine zippers (LIZs) enabling us to identify components of the RyR2 signaling complex and develop novel strategies for studying the function of the channel. The components of the RyR2 macromolecular complex, including PKA, PP1, PP2A, FKBP12.6 and PDE4D3 (phosphodiesterase), are potential novel therapeutic targets for heart failure. We have identified a novel defect in skeletal muscle EC coupling that may contribute to the impaired exercise tolerance in heart failure patients. We now propose the following aims: Aim 1) Determine the in vivo effects of defective regulation of RyR2 by PKA phosphorylation. Ser2809 is the site of PKA phosphorylation in RyR2. We showed that phosphorylation of 3/4 or 4/4 Ser2809 in the tetrameric RyR2 in failing heads causes depletion of FKVBP12.6 from the RyR2 macromolecular complex resulting in defective channels that exhibit increased open probability at low [Ca2+]cyt. Based on these findings we propose to test the hypothesis that PKA hyperphosphorylation of RyR2 and depletion of FKBP12.6 from the RyR2 macromolecular complex contribute to cardiac dysfunction in failing hearts. Aim 2) Determine the role of phosphodiesterases in defective RyR2 regulation in heart failure. Preliminary data summarized in this application show that the phosphodiesterase PDE4D3 is a novel component of the RyR2 macromolecular complex. Our preliminary data further show that PDE4D3 binds to RyR2 via the same targeting protein as PKA, mAKAP, and that the amount of PDE4D3 in the RyR2 complex is reduced in heart failure. On the basis of these preliminary findings we propose to test the hypothesis that defective regulation of PDE4D3 contributes to RyR2 PKA hyperphosphorylation in failing hearts. Aim 3) Identify mechanism(s) underlying impaired skeletal muscle function in heart failure. It is well established that heart failure patients have impaired exercise capacity that is not
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explained solely by the degree of cardiac dysfunction. Our preliminary data show that RyR1 in heart failure skeletal muscle are PKA hyperphosphorylated and depleted of the stabilizing protein FKBP12. In addition preliminary data show that heart failure skeletal muscle from a rat infarct model of failure exhibit early fatigue that correlates with the degree of RyR1 PKA phoshorylation. We propose to test the hypothesis that defective regulation of RyR1 due to PKA hyperphosphorylation and FKBP12 depletion contributes to impaired skeletal muscle function in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR STUDIES OF HEART FAILURE Principal Investigator & Institution: Walsh, Kenneth; Assoicate Professor; St. Elizabeth's Medical Center of Boston 736 Cambridge St Boston, Ma 02135 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The goal of this research is to characterize the post-natal regulatory mechanisms that control heart growth and apply these findings to develop new approaches to treat heart failure. Trophic factors such as growth hormone (GH) and insulin-like growth factor (IGF) are required for normal heart development and have been shown to inhibit and reverse the progression of heart failure. The beneficial effects of GH/IGF on cardiac function are thought to originate, at least in part, from their ability to promote physiological cardiac growth. Furthermore, insulin administered with glucose and potassium (GIK therapy) can decrease the rate of ischemic cell death following acute myocardial infarction, thereby reducing patient mortality. These factors activate the phosphatidylinositol 3-kinase/Akt intracellular signaling pathway, and we have previously shown that the serine-threonine kinase Akt mediates IGF-induced survival signals in cardiac myocytes. Therefore, we hypothesize that Akt signaling is a component of cardiac hypertrophy (Aim 1). In addition, our preliminary data suggest that insulin is an important regulatory of normal post-natal cardiac growth. Together with the finding that insulin is a potent activator of Akt in cardiac myocytes, we hypothesize that insulin regulates cardiac growth during postnatal development through Akt-dependent pathways(Aim 2). We also hypothesize that activation of Akt signaling will improve heart function in models of heart failure by promoting physiological cardiomyocyte hypertrophy (Aim 3). Finally, we hypothesize that the growth-promoting and protective activities of Akt signaling are partly mediated through the regulation of a specific subset of Forkhead transcription factors (Aim 4). Akt-regulated Forkhead factors are implicated in the control of cell growth survival, but they have not been investigated with regard to their regulation and function in the heart. Collectively, the proposed study will contribute to our understanding of the mechanisms that regulate physiological and pathological cardiac growth, and will provide insight for the development of novel approaches to treat heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MONITORING COMMUNITY TRENDS IN HEART FAILURE Principal Investigator & Institution: Goldberg, Robert J.; Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Heart failure is a syndrome of profound clinical and public health importance. Heart failure (HF) is estimated to contribute to nearly 1 million hospitalizations and approximately 250,000 deaths annually in the U.S. The number of new cases of HF in the U.S. is estimated to exceed 400,000 annually. Though
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reliable estimates of the magnitude, incidence, and mortality of HF remain sorely lacking, HF is associated with a grim prognosis. However, little recent data exist, particularly from a community-wide perspective, to determine whether the incidence or survival associated with HF, and the management of this clinical syndrome, has changed over time. This study proposes to examine temporal trends (1995 and 2000) in the incidence rates of HF, its therapeutic management, and changes over time in the hospital and long-term survival of patients with HF from a multi-hospital, populationbased perspective. The study will take place in residents of the Worcester (MA) metropolitan area (1990 census 437,000) and will examine changes over time in these and additional outcomes for patients with validated HF during 1995 and 2000. Complimenting the hospital surveillance of HF, newly diagnosed cases of HF occurring in members of the largest HMO in Central Massachusetts during 1995 and 2000 will be identified and monitored over time. The proposed project will build on the investigators' clinical and epidemiological experience and on data collection efforts and methodologies used in the ongoing community-wide study of coronary heart disease in greater Worcester residents. To accomplish the study objectives, the medical records of residents of the Worcester metropolitan area hospitalized with a discharge diagnosis of HF and related diagnostic rubrics will be individually reviewed and validated according to pre-established diagnostic criteria. The use of traditional criteria for HF as well as development of new criteria for the epidemiological study of HF will be an important focus of this observational study. Records for additional hospitalizations and death certificates will be reviewed to examine trends in long-term survival of discharged hospital patients through the year 2005. The results of this study will provide much needed information about the epidemiology of HF from a more generalizable population-based perspective. Information would be provided about the clinical and descriptive epidemiology of this prevalent and disabling condition in men and women and individuals of different age groups. The proposed surveillance system will provide insights and guidance to public health and clinical efforts of HF and in monitoring trends in this newly emerging chronic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOCARDIAL INFARCTION IN THE POPULATION Principal Investigator & Institution: Roger, Veronique L.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Coronary heart disease (CHD) trends measured via our companion grant R01 HL 59205 document adverse secular trends among the elderly with regards to CHD mortality, MI incidence and post-MI survival. These trends, consistent across all indicators measured, document a shift in the burden of CHD towards older segments of the population and underscore the importance of including all ages to capture age-related differences in outcome and of the access to outpatient data to comprehensively characterize the burden of prevalent CHD. To provide insight into the impact and determinants of CHD trends, which have substantial implications in an aging population, a comprehensive analysis of post-MI outcomes including recurrent ischemic events and heart failure is needed. Indeed, although declining over time, heart failure remains frequent after incident MI and its determinants are not well known. In particular, there is virtually no population-based data on the occurrence of left ventricular (LV) dysfunction and LV remodeling (defined by changes over time in LV geometry), a known precursor of heart failure and on the independent role of age on LV remodeling. The acquisition of such data will be limited by the following factors: 1)
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Older age groups, comprising the highest risk and fastest growing segment of the population, are not included in several surveillance programs. 2) Recent changes in the bio-marker used to diagnose MI clinically will introduce discontinuity in the trends measured through passive surveillance and modify the spectrum of disease labeled as MI. 3) Hospital-based surveillance does not capture outpatient outcomes, an important component of disease prevalence with current shifts away from in-patient care. The exceptional patient-oriented research environment at the Mayo Clinic optimized by the Mayo Clinic Echocardiographic Laboratory and the Rochester Epidemiology Project is a unique resource to address these questions thereby providing a rich experience in patient oriented research to junior investigators. Thus, building on methods implemented through our companion grant, in conjunction with novel and prospective approaches, the objective of this K24 grant is to develop a program to mentor junior investigators in patient-oriented research. The scientific aims of this application are to examine: 1) Using prospectively acquired data, the impact of the implementation of Troponin-based diagnostic algorithms on the incidence of hospitalized MI and on CHD mortality. 2) The trends in the severity, natural history and utilization of cardiac procedures after incident MI and the impact of age on such trends. 3) Using prospectively acquired data, the prevalence and change in echocardiographically determined parameters of LV geometry and function in order to determine the prevalence of LV systolic dysfunction after MI, and the incidence of post-MI LV remodeling. To optimize the training potential of these series of studies and the learning experience of mentees a strong mentoring plan is outlined in details in this revised application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOSIN STRUCTURE /FUNCTION RELATIONSHIPS IN HEART FAILURE Principal Investigator & Institution: Robbins, Jeffrey; Professor & Director; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2002 Summary: Project 5's long term goal is to investigate both the basic biology underlying normal cardiac development and function and the physiological consequences of the myosin heavy chain (MyHC) isoform shifts that occur during the development of heart failure. Many of the signaling pathways activated during compensated hypertrophy and decompensated failure result in fetal gene program activation. Consistent with these data, it has recently been shown that substantial amounts of the alpha-myosin heavy chain gene transcript are present in the normal human heart, and that these levels are dramatically down regulated during heart failure. What is the functional significance of the different cardiac proteins that constitute the main component of the pump? Can modulation of the myosin heavy chain isoform content impact significantly upon the heart's ability to maintain normal cardiac output under normal or pathologic conditions? Project 5 addresses these questions by modulating the myosin isoform content of the mouse heart. SPECIFIC AIM 1 will, using cardiac-specific transgenic expression in the mouse, replace the normal alpha-MyHC isoform with the beta1 betaMyHC protein. Analyses at the molecular, cellular, whole organ and whole animal levels over the lifetime of the transgenic cohorts will provide a comprehensive picture of the consequences of varying myosin isoform content. SPECIFIC AIM 2 will challenge these mice, using both a surgically-induced pressure overload model, and breeding them into a number of genetically defined, cardiac-compromised transgenic lines, in order to define how altered motor content impacts on the progression and severity of
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Heart Failure
cardiac disease. SPECIFIC AIM 3 will test the relevance of the mouse models to the human condition by creating the exact isoform shift that occurs in man in a transgenic rabbit heart. The alpha-MyHC will be linked to the beta-MyHC promoter in order to effect a partial or complete replacement of the normal beta-MyHC in the rabbit heart. The effects at the molecular and cellular levels, as well as hypertrophy and failure. Finally, SPECIFIC AIM 4 will measure both the RNA and protein levels for the alphaand beta- MyHC's in populations with defined heart disease. These data will establish the normal and abnormal levels of these molecules during various, well-defined stages of human cardiac disease. The levels of the V1 and V3 will be correlated with the mechanical properties of the fibers. Together, these experiments will, for the first time, unambiguously establish the structure-function relationships of the cardiac myosin isoforms in the intact animal and will help establish the consequences of altered isoform content on compensated hypertrophy and its progression to heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUREGULIN-ERBB SIGNALING IN MYOCARDIAL REMODELING Principal Investigator & Institution: Sawyer, Douglas B.; Assistant Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: Neuregulins are growth factors that act in a paracrine manner in diverse tissues through the erbB family of receptor tyrosine kinases. A body of work including that from our own laboratory suggests that neuregulin-1 (NRG-1) plays a role in endothelial cell-myocyte crosstalk, and recent clinical data suggests that this system may play a role in the alterations in cardiac structure and function that occur in heart failure. We have used in vitro studies of cardiac myocytes and endothelial cells in primary culture to understand the role of the neuregulin-erbB system in the myocardium. We have found that a recombinant NRG-1 can both activate and inactivate growth pathways in isolated cardiac cells. Moreover we have found that NRG-1 can activate anti-apoptotic signaling as well as increase the expression of cytoprotective antioxidant enzymes in isolated ventricular mycoytes. We have further found that cardiac microvascular endothelial cells express NRG-1alpha, and increase NRG-1alpha expression in response to several stimuli implicated in the pathogenesis of heart failure. These observations have lead to the overall hypothesis that NRG-1-erbB signaling in the adult myocardium maintains myocardial structure and function through the regulation of growth and survival signaling pathways, and is upregulated in response to remodeling stimuli resulting in a dampening of myocardial remodeling responses. We will approach this hypothesis in 5 specific aims, using in vitro studies of cardiac myocytes and endothelial cells, and in vivo models of myocardial remodeling. Collectively this work will help to determine how NRG-1-erbB signaling exacerbates or modulates myocardial remodeling in the setting of myocardial dysfunction, and may ultimately lead to novel therapeutic approaches to interrupt adverse myocardial remodeling leading to the progression of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC OXIDE AND MYOCYTE CELL DEATH IN THE FAILING HEART Principal Investigator & Institution: Anversa, Piero; Professor and Director; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 01-JAN-1991; Project End 31-JUL-2006
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Summary: (provided by applicant) The long-term objective of this application is to identify whether oxidative stress is responsible for the introduction of the phenotypic characteristics of the failing heart and whether interventions capable of interfering with the formation of reactive O2 modify the course of cardiac decompensation. Oxidative damage, mediated by activation of the local renin-angiotensin system (RAS) and enhanced by the reduction of nitric oxide (NO) in the stressed heart, may promote apoptotic and necrotic death of myocytes, endothelial cells, smooth muscle cells and fibroblasts. High levels of oxidative challenge trigger cell necrosis and lower levels induce apoptosis. Cardiac cell death results in loss of muscle, coronary arterioles and capillaries, which coupled with cavitary dilation and wall thinning, lead to defects in myocardial perfusion, ventricular dysfunction and ultimately heart failure (HF). Similar mechanisms may be operative in the diseased human heart during its evolution from moderate to severe decompensation and terminal failure, or in the aging mouse heart in which deletion of the eNOS gene should potentiate the effects of oxidative damage on cardiac cell death. Therefore, production of oxygen radicals may be the common denominator of several pathologic states of the heart including the development of the aging myopathy and HF in the elderly. Conversely, recovery from HF with removal of the inciting stimulus may initiate reactive growth restoring myocytes and vascular structures. Synthesis of NO, reduction of oxidative stress, downregulation of the cellular RAS, decreased cell death and attenuation of Ang II-induced myocyte hypertrophy may all contribute to the recovery process. It is postulated that significant regeneration of functioning myocardium is needed for regression of HF. Myocyte proliferation may be critical for the acute reconstitution of ventricular mass and, thereby, telomere length. Rapidly dividing cells may undergo progressive telomeric shortening, loss of DNA, terminal differentiation and growth arrest. These hypotheses will be tested in a model of HF associated with rapid ventricular pacing in dogs, in human hearts with idiopathic dilated cardiomyopathy in class I-IV NYHA and in an aging mouse model with ablation of the eNOS gene and greater potential for oxidative DNA damage and cardiac cell death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL CYTOKINE SIGNALING IN MYOCARDIAL INJURY Principal Investigator & Institution: Kacimi, Rachid; University of South Dakota 414 E Clark St Vermillion, Sd 57069 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: Cytokines are pleiotropic molecules that elicit their effect locally or systematically in an autocrine or paracrine manner. Recent evidence suggests an important role for cytokines in cardiovascular remodeling in heart failure. Consequently, the overall hypothesis of the present proposal is that the newly discovered cytokines interleukin-15 (IL-15) and interleukin-18 (IL-18) play a role in cardiac cell inflammation, growth, ECM remodeling, and/or survival either alone or synergically with other cytokines or environmental factors (i.e. hypoxia/ischemia). Specific aim 1 will test the hypothesis that IL-1 5 and IL-1 8 play a role in cardiac cell inflammation. Specific aim 2 will test the hypothesis that IL-15 and IL-18 play a role in cardiac cell growth and survival. Specific aim 3 will test whether hypoxia, a major component of ischemia, can modulate IL-15 and IL-18 expression and signaling pathways. In relation to each specific aim, we shall delineate the molecular mechanisms and the specific signaling pathways mediating IL-15 and IL-18 action and whether there is a synergistic action or cross talk. Specific aim 4 will determine the cardiac specific role of IL-15 and IL-18 in vivo and whether selective inhibition prevents
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ischemia/reperfusion induced injury or cardiac remodeling after MI. The overall goal of this project is to understand the signal transduction pathways required for IL-15 and IL18 in mediating cardiac cell function in vitro and in vivo. The study will be performed using an established in vitro model of cultured neonatal cardiac myocytes and fibroblasts, and in vivo models of ischemia and heart failure using state of the art techniques. We anticipate that this investigation will generate new information, which will enhance our understanding of the roles of these novel immunomodulators in cardiac cells. This work will enable us to devise further in vivo studies targeting IL-15 or IL-18 signaling which may help define their pathophysiological role in the setting of ischemia and heart failure. The work may reveal new therapeutic targets to modulate or prevent ischemic disease, cardiac remodeling, and heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL PEPTIDE CONJUGATE TO TREAT CONGESTIVE HEART FAILURE Principal Investigator & Institution: James, Kenneth D.; Nobex Corporation Box 13940, 617 Davis Dr, Ste 100 Durham, Nc 27713 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Congestive heart failure is the only cardiovascular disease that is increasing in prevalence. It is a common cause of death, is accompanied by high indirect costs for treatment, and has a low survival rate upon its onset. The long term goal of this proposal is to develop an orally available drug based on an endogenous peptide to be useful in the treatment of congestive heart failure (CHF). The proposal suggests that a conjugated hBNP may be able to induce the cardiovascular, renal, and endocrine effects that are associated with the native peptide. The most notable advantage of dosing an hBNP conjugate over the native peptide is oral delivery. Covalent attachment of amphiphilic oligomers affords protection from degradative enzymes and facilitates delivery into systemic circulation through the gut wall. The specific aims of this proposal are to synthesize hBNP amphiphilic polymer conjugates, test the conjugates for agonist activity at the human natriuretic peptide receptor A (NPR-A) in vitro, test the conjugates for increased resistance to proteases, and test the conjugates for oral bioavailability in mice. We propose that an oral hBNP conjugate will expand the utilization of this therapeutic to individuals suffering from early stage to overt CHF. Furthermore, an oral hBNP conjugate, by preventing progression from early stage heart failure to more severe phases, may significantly reduce medical costs associated with the treatment of CHF. This Phase I proposal describes a strategy testing three classes of oligomers in order to find the optimal conjugate. Phase II studies will involve pharmacokinetic and pharmacodynamic studies of the most promising candidates arising from Phase I studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OSTEOPONTIN IN HEART & ITS ROLE IN MYOCARDIAL REMODELING Principal Investigator & Institution: Singh, Krishna; Assistant Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 04-APR-1998; Project End 31-MAR-2002 Summary: Extracellular matrix (ECM) contributes significantly to remodeling processes of heart following myocardial damage. My long term goal is to study the biochemical and physiological functions and regulation of osteopontin (OPN), an ECM protein. Our
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preliminary data show that OPN is markedly induced in the mouse heart following myocardial infraction (MI). We have also found that the inducible nitric oxide synthase (iNOS) gene is expressed in the mouse heart following MI, and may therefore be a source of oxidative stress by contributing reactive oxygen species (ROS). We previously demonstrated that OPN inhibits the induction of iNOS gene expression in cardiac myocytes in vitro, and others have provided evidence that OPN can reduce cellular oxidant levels. These observations, taken together, have led us to the hypothesis that, by attenuating nitric oxide (NO)-and ROS-mediated cell damage, OPN serves a protective function during the myocardial remodeling that occurs following MI. To test this hypothesis we will use a recently developed mouse model of chronic myocardial failure caused by coronary ligation, and OPN-knockout mice. We will study morphologic, physiologic and molecular parameters of myocardial remodeling and heart failure and compare them in wild type and OPN-knockout mice subjected to MI. In the first set of experiments, we will examine gross left ventricular (LV) chamber morphology, structure (apoptosis, fibrosis and hypertrophy) and LV function. To address the mechanism by which OPN modifies myocardial remodeling following MI, we will measure the production of NO (by measuring iNOS gene expression and iNOS activity) and superoxide (by lucigenin assay) in wild-type and OPN-knockout mice subjected to MI. Using in vitro cell culture, we will study the involvement of MAPK-pathway in OPNmediated suppression of iNOS expression induced by cytokines. In the third set of experiments, using in situ hybridization and immunohistochemical analysis, we will identify the cell types involved in the expression of OPN in the myocardium following MI. Using cell adhesion, radio- iodination and immunoprecipitation assays, we will identify the receptors for OPN on two major cell types (microvascular endothelial cells and myocytes) of the heart. The identification of cell type(s) involved in the expression of OPN will guide future in vitro studies to determine the mechanism that regulates OPN expression in the myocardium. These studies will advance our understanding of the process of remodeling which occurs after MI and could lead to new therapeutic approaches to heart failure. 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 2001; 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
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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 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: OXIDATIVE STRESS AND POST-MI HEART FAILURE IN DIABETES (PILOT) Principal Investigator & Institution: Hill, Michael F.; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Patients with Diabetes Mellitus (DM) manifest an increased incidence of congestive heart failure (CHF) following myocardial infarction (MI), which presages a reduced survival rate. This has been shown not to be due to a greater extent of infarction associated with DM. The long-term goals of our studies is to understand the mechanisms that contribute to the progressive deterioration of cardiac function and eventual development of CHF in the diabetic heart following an MI. The current project is based on observations that hyperglycemia secondary to diabetes and non-diabetic post-MI heart failure are associated with increased oxidative stress and an antioxidant deficit. Based on these observations, we propose that the coexistence of diabetes and MI exacerbates the existing imbalance between the antioxidant defense system and freeradical production already present in each of these pathologies individually, leading to a quantitative deficiency of antioxidants that predisposes the surviving diabetic myocardium to cumulative, uncontrolled oxidant damage and subsequent failure after MI. The specific aims of the proposed project are: 1) to assess myocardial enzymatic and non-enzymatic antioxidants and concomitant oxidative stress in the remaining, viable diabetic myocardium after MI; 2) to determine the protein expression of the myocardial antioxidant enzymes, and 3) to determine the effects of long-term antioxidant therapy on the occurrence of heart failure following MI in the diabetic heart. The proposed studies will be conducted in streptozotocin (STZ)-induced diabetic rats using the well-
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established coronary-artery ligation model of post-MI heart failure. The objectives of these studies are to delineate the mechanisms by which diabetes adversely affects the functioning of the surviving myocardium after MI and to establish novel therapies aimed at reversing the functional deficit associated with diabetes during the post-MI period. The results of this project will provide a new understanding of the factors that contribute to CHF among diabetics with MI and may form the basis for developing more effective therapeutic interventions for the management of diabetic MI patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE STRESS IN HEART FAILURE: MECHANISMS Principal Investigator & Institution: Hare, Joshua M.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Decreased cardiac energy supply is likely of pathophysiologic significance in the failing cardiovascular system. Energetic efficiency (work for a given oxygen utilization) limits the ability of the heart to pump blood to the circulation both at rest and during times of stress. Oxidative stress, an imbalance between the formation of reactive oxygen species and antioxidant defenses, has been implicated in the development of heart failure not only by direct toxicity but also by altering metabolic pathways. We have recently shown that inhibition of xanthine oxidase (XO), an enzyme that produces superoxide during purine metabolism, profoundly enhances myocardial mechanoenergetic efficiency (the ratio of myocardial work to oxygen consumed) in an animal model of heart failure. This observation is consistent with in vitro findings that XO inhibition augments LV trabecular muscle force generation for a given amount of calcium entry into the cytoplasm. These data support a contributory role for oxidant stress in reducing cardiac myocardial energy utilization. The purpose of the studies in this proposal is to test the hypothesis that the XO pathway inhibits myocardial energetic efficiency by elaborating reactive oxygen species. Experiments will be conducted in conscious animals instrumented to measure LV work and oxygen consumption. We will first determine the contribution and biochemical mechanism of XO to the heart failureassociated increase in oxidative stress. In order to clarify the mechanism of allopurinol action and to assess the participation of another important signaling molecule (nitric oxide) to cardiac energetics, we will test the predictions that other antioxidants mimic, and that inhibition of nitric oxide attenuates the energetic effect of allopurinol. Finally and most importantly, we will determine whether XO inhibition prevents the development of LV dysfunction and whether the beneficial effects of XO inhibition in heart failure are due to its antioxidant properties. These studies are designed to define new mechanisms by which oxidant stress influences integrated cardiovascular performance in heart failure. The results of these studies will clarify pathophysiologic consequences of oxidant stress in heart failure and may have therapeutic implications for humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAILURE
OXIDATIVE
STRESS/ANTIOXIDANT
ENZYMES
IN HEART
Principal Investigator & Institution: Sam, Flora; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005
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Summary: The pathophysiology of heart failure remains incompletely understood. Recent evidence suggests that oxidative stress is increased in clinical heart failure (HF) and may contribute to the pathogenesis of left ventricular (LV) dysfunction. In vitro and in vivo animal studies indicate that reactive oxygen species (ROS) can exert direct myotoxic effects including impairment of contractility and cell death. In animal models of hemodynamic overload leading to heart failure, there is decreased antioxidant enzyme activity, and exogenous antioxidants have been shown to prevent the development of heart failure. The overall goal of this proposal is to determine the extent to which ROS in animal models contribute to the pathogenesis of human heart failure. In Specific Aim 1, we will test the hypothesis that oxidative stress is increased in the myocardium from patients with severe heart failure. Myocardial tissue samples will be obtained at the time of transplantation from patients with severe heart failure. Oxidative stress in the myocardium will be determined by measuring 8-isoprostane and the ratio of reduced/oxidized glutathione. In Specific Aim 2, we will test the hypothesis that there is decreased activity of antioxidant enzymes in the myocardium of patients with severe heart failure. In the myocardial tissue samples obtained for Aim 1, we will measure the activity and expression of superoxide dismutase, glutathione peroxidase and catalase. We will examine the extent to which changes in enzyme activity are due to changes in gene expression vs. post-translational modifications known to inhibit enzyme activity. In Specific Aim 3, we will test the hypothesis that systemic oxidative stress is increased in patients with systolic heart failure, and is associated with more rapid disease progression. In 100 patients with systolic LV dysfunction, followed in the Cardiomyopathy clinics at Boston Medical Center, we will measure 8-isoprostanes in the blood as a marker of systemic oxidative stress at baseline and annually for 3 years. We will correlate 8-isoprostanes with cardiac troponin I (cTn-I), a measure of ongoing myocardial damage and LV end-diastolic diameter by echocardiography (LVEDD), a measure of structural remodeling. In Specific Aim 4, we will test the hypothesis that polymorphisms of MnSOD, the major SOD in the myocardium, lead to increased oxidative stress and more rapid disease progression in patients with heart failure. In patients studied in Aim 3 we will determine the presence of the -9Ala/Val polymorphism of MnSOD that has been associated with reduced enzyme activity. The presence of this polymorphism will be correlated to 8- isoprostanes and remodeling markers from Aim 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REACTIVE INFLAMMATORY SPECIES IN HEART FAILURE Principal Investigator & Institution: Lucchesi, Pamela A.; Associate Professor; Physiology and Biophysics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 01-JUL-1999; Project End 31-AUG-2007 Summary: (provided by applicant): In hearts with volume overload, a complex sequence of compensatory events result in a continual state of extra cellular matrix (ECM) remodeling and by changes in myocyte function and eventually leads to congestive heart failure (HF). Increasing evidence suggests that reactive oxygen (ROS) and nitrogen (RNS) species, collectively termed reactive inflammatory species (RIS), and the enzymes that regulate their bioavailability are associated with contractile failure and myocardial structural damage in end-stage HF models. However, the relationship between RIS and the temporal progression of HF has not been extensively studied. Using an aortocaval fistula (ACF) model in the rat, 3 key, clinically relevant, time points in the temporal progression of volume overload have been rigorously defined in vivo:
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acute (2-5 days), chronic compensated (4-8 weeks), and chronic decompensated (15-21 weeks). Preliminary studies indicate increased tyrosine nitration of myofilament proteins, matrix degrading enzymes and signaling molecules during the acute phase of HF. An imbalance between RIS generating enzymes and antioxidant defenses was also observed acute stage and during the transition to decompensated HF. Moreover, we have found that RIS cause contractile dysfunction in isolated adult cardiac myocytes. This led to the hypothesis that RIS are important mediators of adverse LV remodeling and contractile dysfunction that underlie the development and progression of volume overload-induced HF. Aim 1 will establish a link between reactive inflammatory species and the development and progression of volume overload-induced CHF. RIS will be measured using a combination of microdialysis, ESR (electron spin resonance) and standard biochemical assays. A series of pharmacological interventions and transgenic approaches (iNOS(-/-), myeloperoxidase (-/-), SOD overexpressors) will be used to manipulate RIS levels in vivo. A proteomics approach will used to identify RISmodulated proteins. Aim 2 will determine the mechanisms by which RIS contribute to LV remodeling in ACF-induced HF, with particular focus on ECM turnover in vivo and the regulation matrix metalloproteinase (MMP) activation by cardiac fibroblasts in vitro. Aim 3 will use video edge microscopy, fluorescent Ca 2+ imaging and immunocytochemistry to determine whether altered susceptibility to RIS during HF progression contributes to cardiomyocyte. The proposed investigations are fundamentally important to the development of therapeutic strategies targeted to oxidant-induced injury and may have important implications in the treatment of HF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF ENERGY METABOLISM IN THE FAILING HEART Principal Investigator & Institution: Russell, Raymond R.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) Congestive heart failure causes a switch from adult isoforms of contractile and regulatory proteins to more fetal forms of the proteins. In addition, there is a switch to a "fetal" metabolic pattern in which carbohydrates become the preferred substrate over fatty acids. However, the effect of increased glucose uptake and decreased fatty acid uptake on substrate energy metabolism is not know. Furthermore, the signaling pathway responsible for this switch is unclear. The studies outlined in this proposal will focus on the mechanisms responsible for the switch in substrate preferences as well as the metabolic consequences of that switch in a rat model of heart failure. The proposed studies will test the novel hypothesis that the changes in the high energy phosphates (ATP, AMP, and phosphocreatine) that occur in the setting of heart failure regulate the switch from fatty acid oxidation to carbohydrate utilization through chronic activation of the metabolic stress protein. AMP- activated protein kinase (AMPK). Specifically, the studies will address three major aspects of cardiac metabolism in the setting of heart failure: 1) changes in the uptake and utilization of carbohydrate and fatty acid and their contribution to the citric acid cycle, 2) changes in the expression of key regulatory proteins in carbohydrate (the glucose transporters GLUT1 and GLUT4, hexokinase, phosphofructokinase-2, pyruvate dehydrogenase, and pyruvate dehydrogenase kinase), fatty acid metabolism (fatty acid binding protein, acetyl-CoA carboxylase, carnitine palmitoyltransferase I, and long chain acyl- CoA dehydrogenase), citric acid cycle flux (citrate synthase and alpha- ketoglutarate dehydrogenase), and oxidative phosphorylation (uncoupling protein (UCP)-2 and UCP3) the role of AMPK activation in regulating metabolism in the failing heart. The
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findings of these studies will help to characterize the defects in energy metabolism in the failing heart and aid in the design of therapies that improve energy transduction in the failing human heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF FATTY ACID OXIDATION DURING CARDIAC GROWTH Principal Investigator & Institution: Kelly, Daniel P.; Professor; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2002 Summary: Heart failure is a significant cause of morbidity and mortality in the US. Little is known about the molecular regulatory events involved in the development of cardiac hypertrophy or during the transition to heart failure. During cardiac hypertrophy, the chief myocardial energy substrate switches from fatty acids to glucose; a reversion of fetal energy metabolism. The clinical manifestations of human inborn errors in cardiac fatty oxidation (FAO) enzymes, including hypertrophic cardiomyopathy and heart failure suggest that reduced capacity for myocardial fatty acid utilization leads to hypertrophic cardiac growth and ultimately to reduced ventricular function. Recently, we have shown that the transcription of genes encoding FAO enzymes is repressed in hypertrophied heart via two groups of transcription factors; Sp proteins and the orphan nuclear receptor COUP-TF. This proposal is designed to test the hypothesis that the gene regulatory pathway involved in the repression of FAO enzyme expression during the development of cardiac hypertrophy involves re-induction of fetal transcriptional control and is an integral component of the cardiac growth program. In addition, we hypothesize that the energy substrate switch known to occur during cardiac hypertrophy becomes maladaptive and, thus, promotes development of heart failure. The specific goals of this proposal include; i) characterization of the cis-acting DNA regulatory elements and corresponding transcription factors involved in the repression of genes encoding enzymes involved in two pivotal steps in the FAO pathway using several established cardiac myocyte in vitro hypertrophy systems and an in vivo ventricular pressure overload preparation in transgenic mice (Specific Aims 1, 2), ii) delineation of proximal (upstream) regulatory events responsible for the activation of COUP-TF and Sp proteins during cardiac hypertrophic growth including studies to determine whether COUP- TF is phosphorylated via mitogen activated kinases (Specific Aim 3); and iii) overexpression of the transcription factors in transgenic mice to determine whether activation of this pathway triggers cardiac hypertrophy in vivo and promotes the transition to cardiac failure (Specific Aim 4). The phenotypic characterization of the transgenic mice will include examination of target gene expression, gross and histologic studies of myocyte structure, and in vivo analyses using echocardiography and cardiac MRI. The long-term objective of this project is to develop experimental and, ultimately, therapeutic strategies aimed at the potentially maladaptive energy substrate switches known to occur during development of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RETROGRADE IN SITU ISOLATED CARDIAC GENE DELIVERY Principal Investigator & Institution: Bridges, Charles R.; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005
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Summary: (provided by applicant): Heart failure is an enormous public health problem. This proposal presents an exciting new clinically translatable gene delivery method for the treatment of heart failure. Our technique allows for efficient isolation of the heart in vivo, coupled with the administration of a cocktail of endothelial permeabilizing agents with retrograde re-circulation of recombinant adeno associated virus (rAAV) in the coronary circulation. This technique is predicted to result in a dramatic increase in the transendothelial delivery of rAAV into the cardiac interstitium. In several rodent models, including the normal rat and the BIO 14.6 delta sarcoglycan deficient hamster, using an analogous technique, we have demonstrated exudation of viral vectors into the interstitium and stable, uniform therapeutic and marker transgene expression in skeletal muscle in situ and the heterotopically transplanted rodent heart. We have previously demonstrated global cardiac-specific transgene expression in the canine heart using cardiopulmonary bypass and antegrade vector delivery without the use of inflammatory mediators. In this proposal we develop a new cardiac surgical method allowing for isolation of the heart in situ with retrograde perfusion of the coronary circulation resulting in increased capillary and venular transendothelial pressure gradients. We also design a circuit for retrograde cardiac perfusion with minimum priming volume to further increase circulating vector concentration. Through isolation of the heart our approach uniquely allows for control of the ionic composition and temperature of the delivery vehicle and multiple passes of each rAAV vector through the heart. Based on our preliminary data and published results, each of these factors: retrograde perfusion, cardiac isolation, increased vector concentration, vector recirculation, optimum temperature, ionic composition and the administration of endothelial permeabilizing agents is predicted to significantly improve the efficiency of rAAV-mediated cardiac gene delivery. We will also construct a novel reporter gene construct, rAAV- (MHC)-DAT, allowing for cardiac-specific gene expression and noninvasive quantitative assessment of gene expression using SPECT imaging. Our surgical method and perfusion circuit for isolated retrograde rAAV delivery to the myocardium offers several theoretical advantages over all other available delivery techniques. Further development of this approach may ultimately lead to the development of clinically relevant techniques of therapeutic cardiac gene delivery for the treatment of heart failure of diverse etiologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RGS PROTEIN FUNCTION IN CARDIAC PHYSIOLOGY Principal Investigator & Institution: Muslin, Anthony J.; Professor of Internal Medicine, Cell Bio; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Postnatal mammalian cardiomyocytes respond to mechanical stress, growth factor and hormonal action, and metabolic abnormalities by enlarging, but these cells are unable to proliferate for reasons that are not understood. The clinical consequences of human cardiac hypertrophy are very significant and include the development of serious cardiac arrhythmias, of diastolic dysfunction that can result in pulmonary edema and fluid overload, and of congestive heart failure. Intracellular signaling cascades play a major role in the development of cardiac hypertrophy. Several lines of evidence support the role of G proteins in the development of cardiac hypertrophy. RGS (regulator of G protein signaling) proteins were recently found to be GTPase activating proteins (GAPs) for heterotrimeric G proteins. In this proposal, we will outline experiments to test the hypothesis that RGS proteins determine the responsiveness of cardiomyocytes to extracellular stimuli, and that RGS gene expression can be increased
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as an adaptive mechanism to limit G- protein-mediated signal transduction. We will examine the expression pattern of RGS family members in animal models of cardiac hypertrophy and congestive heart failure. We will determine the relative ability of RGS family members to block cardiomyocyte signal transduction and hypertrophic growth. We will determine whether RGS4 inhibits cardiac hypertrophy in a transgenic mouse model in response to provocative stimuli. Finally, we will determine whether dominant negative mutant forms of RGS2 and RGS4 promote cardiomyocyte signal transduction and hypertrophic growth. These experiments will help to establish the role of RGS proteins in the pathophysiology of cardiac hypertrophy and may have an impact on future treatment of patients with this disorder and those in whom hypertrophy has progressed to heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RIGHT VENTRICULAR DYSFUNCTION AND TREATMENT Principal Investigator & Institution: Semigran, Marc J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114
Assistant
Professor;
Timing: Fiscal Year 2001; Project Start 12-APR-1999; Project End 31-MAR-2004 Summary: Heart failure represents the results of a variety of cardiovascular diseases in which the initial insult to the myocardium may either be identifiable, such as a myocardial infarction, or unknown, such as in dilated cardiomyopathy. In either case, the occurrence of injury to the myocardium leads to an inexorable course of myocardial dysfunction. While most previous investigations have concentrated on the abnormalities in left ventricular function, there is evidence that right ventricular (RV) function is a more important determinant of patients symptoms and prognosis. Few therapies currently exist to improve RV performance, as currently used systemic vasodilator therapy can cause hypotension when nonselective pulmonary vasodilators are added to a patient's therapeutic regimen. Nitric oxide (NO) activates vascular smooth muscle cell soluble guanylate cyclase leading to vasodilation. The vasodilator effect of NO is limited in time by its rapid binding to, and inactivation by hemoglobin. In preliminary studies, inhaled NO has been demonstrated to be a selective pulmonary vasodilator which can improve cardiac performance and exercise capacity in heart failure patients. The goal of this proposal is to combine type 5 (cGMP- specific) phosphodiesterase inhibiton with inhaled NO to: 1. Assess the acute alterations in right ventricular function, overall cardiac performance and exercise capacity in heart failure patients treated with the combination of inhaled NO and the type 5 phosphodiesterase inhibitor sildenafil. 2. Assess the acute and chronic effects of selective pulmonary vasodilation with inhaled nitric oxide and type 5 phosphodiesterase inhibition on pulmonary artery resistance and morphology in patients with pulmonary hypertension due to pulmonary vascular disease or to left heart failure. 3. Assess the effects of acute and chronic pulmonary vasodilator and the subsequent decrease in wall stress on the activity of proteins which regulate myocyte apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RNA ISOLATION FROM HEART SAMPLES FOR EXPRESSION ANALYSIS Principal Investigator & Institution: Perreault-Micale, Cynthia L.; Gwathmey, Inc. 763 E Concord Ave Cambridge, Ma 02138 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JAN-2004
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Summary: (provided by applicant): The overall objective of this study is to determine the changes in gene expression responsible for the development of endstage heart failure. The first step will be to construct two interactive databases 1) for human heart, vascular and skeletal muscle samples and 2) for similar samples from rodent models of heart failure. Gwathmey, Inc has collected hearts and blood vessels, and all the corresponding medical records from human samples that are stored as paper copies only. The investigators propose to develop a database to aid in the management of the tremendous amount of medical information that is available with each human heart. The proposed approach will make it possible for us to access all patients' records according to diagnosis, age, gender, existing medical conditions, medications, race, serology, and other specific clinical tests. Also the investigators will create a database of commonly used rat models of heart failure for comparison. Similarly they will be able to recall heart samples from animal models based on age, gender, and severity of heart failure as well as cause of the heart disease. The human database will allow for continued expansion with an on-line update upon receiving new heart tissue that occurs on a weekly basis. The second goal of this study is to extract total and polyA RNA from all of the normal and diseased heart samples. Initially, the investigators intend to extract RNA from about 400 left ventricular control and myopathic human and rodent hearts that will represent the most common disease states (dilated, ischemic and hypertensive myopathies), as well as appropriate controls. The investigators will examine the quality, purity and quantity of RNA obtained and enter it into both databases so that they can keep a running log of the results. The human and rodent heart databases, in combination with the extensive collection of high quality RNA, will be an extremely valuable research tool and product available to the investigators and clients for innovative studies of differential gene expression during heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF MYOSTATIN IN CARDIAC HYPERTROPHY AND FAILURE Principal Investigator & Institution: Rosenzweig, Anthony; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 21-SEP-1998; Project End 31-JUL-2007 Summary: (provided by applicant): Cardiomyocyte hypertrophy increases the risk of adverse clinical events and is a common prelude to cardiac dilatation and heart failure. However, little is known about the counter-regulatory mechanisms controlling cardiomyocyte hypertrophy or the mechanisms mediating the transition to heart failure. Using microarray analysis of hypertrophic hearts from Akt transgenic mice, we have recently identified dramatic induction of myostatin, a highly conserved negative regulator of skeletal muscle growth, not previously known to play a role in the heart. Preliminary in vitro data suggest myostatin expression exerts a potent anti-hypertrophic effect in cardiomyocytes. However, the long-term effects of inhibiting cardiomyocyte hypertrophy in this way are unknown. The goals of the current proposal are to examine the role of myostatin in both in vitro and in vivo models of cardiac hypertrophy and failure. This proposal is based on three hypotheses: 1) that myostatin is an endogenous negative regulator of cardiac hypertrophy, 2) that cardiac myostatin activity is induced by cardiac hypertrophy in vivo, and that 3) myostatin expression ultimately contributes to the transition from hypertrophy to dilatation and heart failure by enhancing cardiomyocyte apoptosis. To test these hypotheses, we will study the effects of myostatin inhibition or deletion, as well as cardiac expression of myostatin, in both in vitro and in vivo models of cardiomyocyte hypertrophy, apoptosis, and failure. In
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Specific Aim 1, we will examine the effects of myostatin expression in vitro on cardiomyocyte hypertrophy and apoptosis. In Specific Aim 2, we will define the downstream signaling pathways involved. In Specific Aim 3, we will evaluate the longterm effects of myostatin deletion on the heart both at baseline and in models of cardiac hypertrophy and failure in vivo. In Specific Aim 4, we will examine the effects of transgenic cardiac expression of myostatin or the inhibitory myostatin propeptide, at baseline and in models of cardiac hypertrophy. Understanding the role of specific pathways in cardiomyocyte hypertrophy may provide novel therapeutic approaches for the management of cardiac hypertrophy and heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SAFETY AND EFFICACY OF SERTRALINE FOR DEPRESSION CHF Principal Investigator & Institution: Krishnan, Ranga R.; Chairman and Professor; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 20-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The significance of co-morbid depression upon the medically ill has recently been recognized in the medical literature. Higher prevalence rates of mood disorders above that of the normal population has been found in patients who suffer from chronic medical illnesses, including vascular disease (cerebrovascular and coronary artery disease). Additional work has shown increased in-patient hospitalizations, cost of care, morbidity and mortality in these patients. More than 2 million United States citizens suffer from congestive heart failure (CHF), accounting for the highest category for hospitalization in the Medicare population, with annual expenses exceeding $10 billion. One leading source of heart failure is ischemic heart disease. Despite knowledge that depressive disorders lead to increased morbidity, mortality and poorer outcomes in ischemic heart disease, little is currently known about the association of CHF and depression. There is evidence that the rate of depression may be high in the CHF population, but no studies have addressed the impact on morbidity and mortality in CHF patients when depression is adequately treated. Funding is requested for a two site, prospective placebo treatment of patients with congestive heart failure and clinically diagnosed major depression. Patients will be enrolled in this study with clinically diagnosed heart failure of NYHA functional > II. Patients will be interviewed and evaluated for major depression by use of the protocol developed by the NIMH-supported Duke Center for the Study of Depression in the Elderly. This includes sections that assess depressive symptoms, psychiatric co-morbidity, cognitive status, functional status and disability, daily and chronic stress, and social support, the longitudinal component of this study will include collecting data on all enrolled subjects. Information collected in these follow-up contacts will include deaths, rehospitalizations, cardiac events, functional status/quality of life measures, and level of depressive symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SCIENTIFIC CONFERENCE ON THE FAILING HEART Principal Investigator & Institution: Izumo, Seigo; Director of Cardiovascular Research; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 22-AUG-1999; Project End 31-JUL-2004 Summary: We plan to hold the third American Heart Association (AHA) "Failing Heart" Conference entitled "Scientific Conference on Molecular, Cellular, and Integrated Physiological Approaches to the Failing Heart" on August 18-22, 1999 at Snowbird
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Conference Center in Salt Lake City, Utah. This conference is sponsored by the AHA's Councils on Circulation and Basic Science. Two previous "Failing Heart" conferences were held quite successfully in Asilomer, CA in 1993 and in Salt Lake City in 1996. Conference Description - With the advent of transgenic and gene- targeting technologies as well as the progress made in murine cardiac physiology and imaging, the field of cardiovascular science is rapidly transforming into a truly integrated science of molecular biology, developmental biology, genetics, morphology, pharmacology, and physiology. This four-day conference includes lectures, discussion, workshops, poster presentations focusing on new development on heart failure research, and hosts a New Investigator Award competition for trainees and junior investigators and Cardiovascular Research Prize Competition for newly established investigators. Seventy-five (75) invited speakers will give presentations at 23 plenary sessions, two workshops, and three extended poster sessions. The meeting format is designed to provide opportunity for intense interaction among participants during the sessions and breaks. Conference Objectives - The purpose of the conference is to l) provide an update regarding the advances in molecular genetics of cardiomyopathy and cardiac failure, 2) characterize new cellular mechanisms associated with altered signal transduction in myopathic hearts, 3) review advances with respect to new transgenic and gene targeted models of cardiomyopathy, 4) discuss new ways to explore transgenic murine models using integrated physiological approaches, and 5) discuss ways to analyze transgenic mouse hearts by various morphological and imaging approaches. Anticipated Participants - Cardiologists, cardiovascular physiologists, pharmacologists, cell biologists, biochemists, clinical investigators, and other scientists interested in heart failure are invited to submit an abstract for poster presentation. We will discount the registration fee by 75% for trainees and 20 travel awards will be provided for trainees and junior investigators submitting outstanding abstracts. At least 300 participants are expected. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SERCA2A ABNORMALITIES AND CHAPERONES IN HEART FAILURE Principal Investigator & Institution: Del Monte, Federica; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The purpose of this Clinical Investigator Development Award is to prepare the applicant for a career as an independent investigator in cardiology. The applicant has developed a great interest in the cellular dysfunction observed in heart failure. As a Ph.D. student, the PI has closely examined the role of P-adrenergic receptor function and calcium handling in animal models of hypertrophy and heart failure as well as in single myocytes isolated from failing and non-failing human hearts. The applicant proposes to acquire additional skills in biophysics and molecular biology in the context of a project that builds on her experience on somatic gene transfer and contractile dysfunction in failing cardiac myocytes. Congestive heart failure has reached epidemic proportions in the United States. One of the key abnormalities in human heart failure is a defect in intracellular Ca2 handling associated with abnormal Ca2 reuptake into the sarcoplasmic reticulum (SR) in both human and experimental heart failure. More specifically, deficient Ca2 reuptake has been associated with a decrease in the expression and activity of SR Ca2ATPase (SERCA2a). The applicant has shown that overexpression of exogenous SERCA2a improves contractility in failing human cardiomyocytes and survival in
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experimental models of heart failure. However, beyond the decrease in SERCA2a protein expression, the transporter activity was found to be decreased in failing hearts. In addition, changes in card ioprotective proteins that facilitate transport, folding of newly synthesized or refolding of damaged proteins may also occur. The aims of this proposal are to investigate the structure function relationship of the transporter in failing hearts as well as to examine the family of cardioprotective proteins involved in folding SERCA2a. In this application, we propose to test the following hypotheses: 1) SERCA2a is structurally abnormal contributing to its deficiency in transporting Ca2 in failing hearts and 2) chaperone proteins such as Glucose Related Proteins (GRPs) GRP 78 and 94 may play an important role in the structural integration or repair of SERCA2a in normal and failing hearts. To test these hypotheses, three specific aims are proposed: In Specific aim 1: the crystal structure of SERCA2a will be characterized, in specific aim 2: the role of chaperone proteins will be examined through somatic gene transfer in non failing and failing human cardiomyocytes, and in specific aim 3: the role of chaperone proteins will be examined in vitro and in vivo in an animal model of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKELETAL MUSCLE PROTEIN METABOLISM IN HEART FAILURE Principal Investigator & Institution: Toth, Michael J.; Assistant Professor; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The PI's short-term goal is to obtain the training required to complete the proposed studies. His long-term goal is to become an independent researcher and to develop his own research program investigating the mechanism of weight loss and skeletal muscle atrophy in healthy and diseased elderly. During this award, the PI will gain experience in several laboratory and clinical research techniques associated with the measurement of skeletal muscle protein metabolism in humans using stable isotopes, arterio-venous balance and skeletal muscle biopsy methodologies. The mentoring team and the facilities available within the College Of Medicine are an ideal environment for the training of junior scientists. Patients with chronic heart failure frequently experience skeletal muscle atrophy which limits functional Capacity by reducing muscular strength and endurance. Moreover, muscle atrophy is associated with increased morbidity and mortality. The primary goal of the proposed studies is to determine the pathophysiological mechanisms underlying the loss of skeletal muscle mass in patients with chronic heart failure. The primary hypothesis is that increased skeletal muscle protein Catabolism in the postabsorptive state and reduced skeletal muscle protein anabolism in the postprandial state promotes skeletal muscle atrophy in heart failure patients. We will measure skeletal muscle protein balance (i.e., difference between synthesis and breakdown) using a combination of arteriovenous balance and stable isotope tracer techniques under postabsorptive (24 hour fast) and simulatedpostprandial conditions (euglycemic hyperinsulinemia with concomitant hyperaminoacidemia) in cachectic and noncachectic heart failure patients and healthy controls. We will assess skeletal muscle protein balance during these experimental manipulations to probe for defects in postabsorptive and postprandial muscle protein balance that may contribute to skeletal muscle atrophy. In this design, noncachectic heart failure patients will serve as a diseased control group and healthy controls as a non-diseased control group. The secondary goal is to measure and compare the synthesis rate of skeletal muscle myosin heavy chain between heart failure patients and healthy controls and examine its relationship to reduced muscular strength in heart failure patients. Our secondary hypothesis is that reduced synthesis of myosin heavy
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chain in heart failure patients will be related to reduced muscular strength. The fractional synthetic rate of myosin heavy chain will be assessed by measuring the incorporation of [1,2- 13C2]leucine into skeletal muscle protein. These experiments will provide new information regarding the pathophysiological mechanisms responsible for the loss of skeletal muscle mass and strength in heart failure patients. 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 2001; 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 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
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Project Title: SPECIALIZED CENTER OF RESEARCH IN HEART FAILURE Principal Investigator & Institution: Dorn, Gerald W.; Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 14-FEB-2000; Project End 31-JAN-2005 Summary: Cardiac hypertrophy is the common adaptive stress-response of the heart to multiple mechanical or biochemical stimuli. Although initially compensatory, hypertrophy ultimately decompensates leading to the syndrome of congestive heart failure. A single critical transducer of hypertrophy/heart failure has not been identified, and probably does not exist. Rather, cardiac hypertrophy and failure are the culmination has not been identified, and probably does not exist. Rather, cardiac hypertrophy and failure are the culmination of various stimuli activating multiple signaling cascades, each of which modify the end response. In determining the mechanisms for hypertrophy progression to heart failure we hypothesize that the molecular and cellular consequences of adaptive hypertrophy ultimately cause its decompensation and transition to heart failure. The five Projects of this SCoR renewal each examine different, but inter-related aspects of the putative integrated hypertrophy signaling pathways. Dr. Dorns' project uses a novel approach of PKC isoform- specific activation and inhibition to delineate the roles of different PKCs in cardiac adaptation. Project 2 will continue its highly successful survey of beta1 and beta2 adrenergic receptor polymorphisms in heart failure, and further define the influence of receptor variants on cardiac physiology, and the response to beta blockade. Dr. Molkentins' Project investigates a novel hypertrophy signaling pathway, calcineurin/NFAT-3, to determine its role in cardiac adaptation and maladaptation. Project 4 examines the function of sarcoplasmic calcium cycling proteins in normal and failing mouse hearts and characterizes naturally occurring human genetic polymorphisms of phospholamban and the sarcoplasmic reticulum calcium ATPase. Project 5 will examine the notion that cardiac hypertrophy leads to heart failure in part due to an increase in the relative expression of beta versus alpha myosin heavy chain. Each of the Projects takes advantage of studies performed in cultured cells, transgenic mice or rabbits and humans, and are supported by a Mouse Physiology Core which provides a physiological modeling and hemodynamic analysis, and a Clinical Core which provides information and physiological assessment of cardiac function of heart failure patients, and collects human myocardial specimens for molecular and biochemical assays proposed in all the Projects. We believe this thematically linked, multi-disciplinary research program will continue to break new ground in increasing our understanding of the pathogenesis and optimal management of human heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 2001; 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
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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 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 SUDDEN CARDIAC DEATH Principal Investigator & Institution: Marban, Eduardo; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 20-JAN-1995; Project End 31-DEC-2004 Summary: Sudden cardiac death accounts for 30-50% 0f heart failure mortality. This proposal, which is the continuation of an existing SCOR program in Sudden Cardiac Death, investigates the biological basis of altered excitability in heart failure and how predisposes to fatal ventricular arrhythmias. The SCOR is motivated by the following central hypothesis: Abnormalities of ionic currents and calcium handling render repolarization unstable in failing myocardium, increasing spatiotemporal variability of repolarization and predisposing patients with heart failure to sudden death. This hypothesis has been tested and validated extensively in the first five years of the program. We now propose to probe the biological basis of the abnormal repolarization, with a view to developing novel strategies for the identification of patients at high risk. Our program features a central animal model (pacing tachycardia canine heart failure) as well as tissue and myocytes from explanted human hearts. The program consists of five projects and five cores. Project 1, directed by Eduardo Marban, will use gene
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transfer and cell fusion to dissect the molecular determinants of cardiac repolarization. Project 2 focuses on L- type calcium channel inactivation. Project 2 focuses on L-type calcium channel inactivation under the leadership of David Yue. Project 3, directed by Gordon Tomaselli, investigates the relative roles of voltage- dependent and calciumdependent mechanisms in the action potential prolongation of heart failure. Project 4 probes the neurohumoral modulation of electromechanical remodeling in heart failure, under the directorship of David Kass. Project 5, led by Ronald Berger, examines temporal QT interval variability as a predictor of severe arrhythmias and sudden cardiac death in patients. The five cores will provide support in the following areas: administrative matters, molecular genetics and vectors, animal models and cells, human cells and tissue, and quantitative modeling. The program in its first five years has been highly productive and interactive. The proposed continuation combines existing strengths with new approaches in a strongly synergistic manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STICH TRIAL RADIONUCLIDE CORE LABORATORY Principal Investigator & Institution: Bonow, Robert O.; Goldberg Professor of Medicine; Medicine; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2007 Summary: (provided by applicant): The Surgical Treatment for Ischemic Heart Failure (STICH) multicenter international randomized trial addresses two specific primary hypotheses in patients with clinical heart failure (HF) and left ventricular (LV) dysfunction who have coronary artery disease (CAD) amenable to surgical revascularization: 1) Coronary artery bypass grafting (CABG) with intensive medical therapy (MED) improves long-term survival compared to MED alone; 2) In patients with anterior LV dysfunction, surgical ventricular restoration (SVR) to a more normal LV size improves survival free of subsequent hospitalization for cardiac cause in comparison to CABG alone. Important secondary endpoints include morbidity, economics, and quality of life. Core laboratories for cardiac magnetic resonance (CMR), echocardiography (ECHO), neurohormonal/ cytokine/genetic (NCG), and radionuclide (RN) studies will ensure consistent testing practices and standardization of data necessary to identify eligible patients and to address specific questions related to the primary hypotheses. Over three years, 50 clinical sites will recruit 2,800 consenting patients with HF, LV ejection fraction (EF) 60 ml/m2 and akinesia >35% of the anterior LV wall. The 600 patients estimated to be eligible for SVR but ineligible for randomization to medical therapy will be evenly randomized to CABG with or without SVR. Of the 2,200 consenting patients eligible for medical or surgical therapy, the 1,600 not SVR eligible will be evenly randomized between MED only and MED with CABG. The remaining 600 patients also eligible for SVR will be randomized between three treatments of MED only, or MED + CABG, or MED + CABG + SVR. Registries of clinical information will be maintained on eligible patients who decline trial entry. At fourmonth intervals for a minimum of three years, all randomized patients will be followed by a clinical visit and registry patients will be followed by telephone. Appropriate subgroups of randomized patients will have core laboratory studies repeated at specified follow-up intervals. In the patients randomized to MED with or without CABG, CABG with MED is hypothesized to demonstrate a >20% reduction in the primary endpoint of all-cause death with an 89% power from the projected 25% threeyear mortality for MED. In the SVR-eligible patients, CABG + SVR is hypothesized to show a 20% advantage with 90% power in the endpoint of survival free of hospitalization for cardiac cause projected to be 50% at three years in patients receiving
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CABG without SVR. Definition of efficacy of potential therapies and their mechanisms of benefit by the STICH Trial is certain to inform future choice of therapy and thereby extend and improve the quality of lives of millions of patients who now suffer from ischemic HF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 REMODELING
UBIQUITIN-PROTEASOME
SYSTEM
IN
CARDIAC
Principal Investigator & Institution: Wang, Xuejun; University of South Dakota 414 E Clark St Vermillion, Sd 57069 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-AUG-2007 Summary: A long term goal of this proposal is to delineate the mechanisms by which protein surplus cardiomyopathies (PSCs) progress to congestive heart failure. PSCs are an emerging group of cardiomyopathies. Crystallinopathy caused by the mutation of the alphaB-crystallin (CryAB) gene, often presents as desmin-related cardiomyopathy (DRC) and exemplifies PSCs. DRC is characterized by aberrant desmin aggregation in muscle cells and this aggregation appears to play a central role in DRC pathogenesis.
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Notably, similar protein aggregates were also observed in human congestive heart failure (CHF) resulting from idiopathic dilated cardiomyopathy, a common heart disease. However, it remains unclear how abnormal protein aggregation affects myocyte functions. The current proposal focuses on the ubiquitin-proteasome system (UPS) mediated protein turnover, a cellular process essential to virtually all aspects of cell function. The central hypothesis is that aberrant protein aggregation characteristic of DRC impairs proteolytic function of the UPS, representing a nodal pathogenic process in PSCs. These specific aims will be pursued: (1) To test whether CryAB has an obligatory role in UPS function and to define a correlation (likely a causal relation) between aberrant protein aggregation and UPS impairment in intact mice. The underlying hypothesis is that aberrant protein aggregation instead of loss-of-function of CryAB impairs the UPS in crystallinopathic hearts. (2) To test a cause-effect link between aberrant protein aggregation and UPS impairment in cell culture. This is to test the hypothesis that formation of protein aggregates through expression of a mutant CryAB is sufficient to compromise UPS function. (3) To discover the identities of ubiquitylated proteins accumulated in crystallinopathy mouse hearts lusing proteomics. Underlying hypothesis is that accumulated ubiquitylated proteins include structural proteins and physiologically important regulatory proteins. 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 2001; 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 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
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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: TRANSCRIPTION REGULATION IN HEART FAILURE Principal Investigator & Institution: Sepulveda, Jorge L.; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): CANDIDATE: Dr. Sepulveda has an MD from the University of Lisbon and a PhD in Cell Biology from Baylor College of Medicine. He completed residency in Clinical Pathology and fellowship in Transfusion Medicine at Baylor, and served full time since 1999 as Assistant Chief of Laboratory at the Houston VAMC. In 8/2000 he joined the Department of Pathology at the University of Pittsburgh, wherein 80 percent of his time is protected for research. Dr. Sepulveda goals are to develop a comprehensive research program to effectively dissect the pathways leading to heart failure (HF) and to explore mechanistic interventions aimed at modulating cardiomyocyte phenotypes and improving the natural history of heart failure. Dr. Sepulveda has start up funds, adequate laboratory space and access to the resources of Pathology, Cardiology, and core facilities at the University of Pittsburgh. BACKGROUND: Patients with HF have a 5-year survival rate of less than 50 percent. During progression of HF, cardiomyocytes undergo neuroendocrine stimulation. Different stimuli result in different hypertrophy phenotypes with expression of different isoforms of cardiac proteins. Hypertrophy temporarily results in increased contractility but ultimately cardiomyocyte remodeling, elongation and contractile failure occur. HYPOTHESIS: I. During hypertrophic stimulation, changes in the combinatorial activity of transcription factors SRF, GATA4 and Nkx2-5 leads to modulation of transcription of various isoforms of cardiac-specific genes. II. In decompensated HF, down-regulation of SRF, GATA4 and Nkx2-5 results in insufficient transcription of contractile proteins and consequent inotropic failure. AIM 1: To test the hypothesis that changes in levels of SRF, GATA4 and Nkx2-5 occur during HF progression, by measuring mRNA and protein levels in cardiomyocytes stimulated with hypertrophic agents, and in heart extracts from tumor necrosis factor-alpha transgenic mice (a model of HF). AIM 2: To test the hypothesis that functional changes in SRF, GATA4 and Nkx2-5 occur during hypertrophic stimulation and HF progression. Function will be characterized by measuring DNA binding affinity, transcriptional activation and interactive proteins. AIM 3: We will inactivate SRF, GATA4 and Nkx2-5 to test the hypothesis that these factors are critical for regulating transcriptional switches during hypertrophic stimulation of cardiomyocytes. We will measure the changes in hypertrophic phenotype and specific target genes in cardiomyocytes stimulated with hypertrophic agents. IMPACT: These studies are essential to understand the molecular mechanisms that underlie cardiomyocyte phenotype changes in HF progression and will have a general impact on clarifying transcriptional regulatory pathways in cardiomyocytes. These advances in the understanding of the mechanisms of HF may suggest diagnostic, therapeutic and preventive strategies to help modify the currently dismal prognosis of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TROPONIN MODULATION IN HEART FAILURE Principal Investigator & Institution: Solaro, R J.; Professor and Head; Physiology and Biophysics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 15-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from the applicant's description): Experiments proposed here test hypothesis that alterations in the structure, function, and regulation of cardiac troponin I (cTnI) and cTnT contribute to the evolution and end-stage pathology of heart failure. The long term objective is know how myofilament remodeling and covalent modulation play a role in the evolution of hypertrophy/failure in human hearts. Aims #1, #2, and #3 address the questions: Can altered tension and economy of myofilaments from human hearts in end-stage failure be rescued by replacing components of the Tn complex with recombinant proteins? What is the nature of the thin filament alterations in human heart failure? Are there changes in protein phosphorylation of specific sites on cTnI or isoform population of cTnT? How do these changes alter force and ATPase rate in reconstituted preparations? Aim #4 addresses the question: What is the specific role of protein kinase C (PKC) sites on cTnI in the development of hypertrophy and failure in response to hemodynamic stress of pressure overload? The approach to these objectives involves the use of procedures for exchanging thin filament proteins in the intact force generating lattice, and for isolating Tn complex from small heart tissue samples. Recombinant proteins are prepared in an unphosphorylated state and specifically phosphorylated at PKC and PKA sites. Gel electrophoresis, immunoblotting and antibodies that recognize phosphorylated forms of cTnl are used to detect changes in the Tn complex. To test the role of specific PKC sites on cTnI in the evolution of hypertrophy and failure, mice harboring transgenes expressing a mutant form of cTnl (lacking PKC sites at Ser 43 and Ser 45) and slow skeletal TnI (lacking a PKC site at Thr 144 in the inhibitory peptide) are stressed by pressure overload. These experiments provide crucial information on the mechanisms of heart failure and on the potential value of developing pharmacological approaches to the inhibition of the PKC pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: T-TUBULES AND L-TYPE CALCIUM CHANNELS IN HEART FAILURE Principal Investigator & Institution: Kamp, Timothy J.; Assistant Professor; Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 31-MAY-2003 Summary: (adapted from the applicant's description): Congestive heart failure results in substantial structural and functional changes at the level of cardiac myocytes. Preliminary results indicate that the t-tubular network is severely depleted or absent in failing canine and human myocytes. This observation has important functional consequences for excitation-contraction (E-C) coupling (which requires close opposition between surface membrane L-type Ca channels (DHPRs) in the t-tubule membrane and Ca release channels (RyRs) in the SR) and beta-adrenergic signal transduction. The general hypothesis of the proposed research is that sub-cellular remodeling of the ttubule system and junctional domains results in contractile failure and abnormal betaadrenergic regulation in failing ventricular myocytes. This general hypothesis will be tested in myocytes obtained from a tachycardia pacing-induced dog model and confirmed on human cells obtained from patients undergoing cardiac transplantation. The 5 specific aims of the proposed research are: 1) characterization of the t-tubule system density in failing and control hearts using 2-photon and confocal microscopy, 2)
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quantification of DHPRs in failing and control hearts using electrophysiological and biochemical techniques, 3) define the mechanism of uncoupling of the DHPR and RyR in failing myocytes, 4) determine the mechanism of uncoupling of beta-adrenergic receptors and DHPRs, and 5) perform confocal immunolocalization studies of DHPR subunits, RyR, beta-adrenergic receptors and G-proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VEGF TRANSFER TO PROMOTE ANGIOGENESIS IN ADVANCED CHF Principal Investigator & Institution: Mccarthy, Patrick M.; St. Elizabeth's Medical Center of Boston 736 Cambridge St Boston, Ma 02135 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: The clinical investigations outlined in this Project are designed to test the hypothesis that direct intramyocardial injections of naked DNA encoding for vascular endothelial growth factor (phVEGF165) in patients with advanced heart failure is safely tolerated and may in some patients lead to improvement in their clinical status. The clinical trials that we have proposed incorporate a strategy that is designed to address patients in whom all medial measures to treat advanced congestive heart failure (CHF) have failed, leaving these patients in need of cardiac transplantation. Owing to the mismatch that currently exists between the number of patients in need of cardiac transplantation and the number of available donors, implantation of a left ventricular assist device (LVAD) Is often required for patients as a so- called "bridge" to transplantation. It is this population of patients-those undergoing LVAD implantation for advanced heart failure-that re intended to be addressed in the current Proposal. For the purpose of our clinical studies, these patients have been divided into two large subgroups, based on associated evidence on extramural coronary artery disease (CAD). Accordingly, the specific aims of this Proposal are as follows: 1. Specific Aim #1: To evaluate the safety and impact of phVEGF/165 gene transfer on LV function in patients with CHF due to coronary artery disease. 2. Specific Aim #2: To evaluate the safety and impact of phVEGF165 gene transfer on LV function in patients with CHF due to idiopathic dilated cardiomyopathy, excluding patients with significant narrowing of the extramural coronary arteries of primary valvular heart disease. 3. Sp4ecific Aim #3: To evaluate the efficacy of phVEGF gene transfer to allow for LVAD bridge-to-recovery (BTR) as an alternative to transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: XANTHINE OXIDASE INHIBITOR FOR CONGESTIVE HEART FAILURE Principal Investigator & Institution: Novorozhkin, Alex; Inotek Pharmaceuticals Corporation 100 Cummings Ctr, Ste 419E Beverly, Ma 01915 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-DEC-2002 Summary: (provided by applicant): Congestive heart failure (CHF) is a major market opportunity for therapeutics that targets the fundamental etiology of the ventricular injury. Although the pathogenesis of CHF is complex, recent data suggest an inflammatory basis secondary to free radical generation by the purine degradative enzyme xanthine oxidase (XO). In the well-established pacing dog model, which produces a dilated cardiomyopathy and many of the classic features of CHF, XO activity is 4-fold increased and the weak XO inhibitor allopurinol increases dP/dt(max), preload-recruitable stroke work, and ventricular elastance. In heart failure dogs, but not
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controls, allopurinol decreases MVO2 and substantially increases mechanical efficiency. Taken together, these data indicate that XO inhibition is uniquely inotropic, increasing myocardial contractility while simultaneously reducing cardiac energy requirements. The resultant boost in myocardial contractile efficiency may prove beneficial in the treatment of clinical CHF. The market for allopurinol is limited by its infrequent but severe side-effects. We now report the discovery of a non-purine class of XO inhibitors that is 1,000-fold more potent than allopurinol. Preliminary data confirm that a prototype of this class profoundly reduces inflammation in experimental models of acute lung injury and enterocolitis. The central objective of this Phase I grant proposal is to establish in vivo proof of principle that the lead candidate dose-dependently improves contractile function in the classic dog model of CHF induced by chronic pacing. We will then define the pharmacodynamic profile of XO therapy, begun after the establishment of CHF. Cardiac contractility will be assessed using left ventricular pressure-volume analysis, dP/dT, stroke volume, and ejection fraction. The classic weak XO inhibitor allopurinol will be included in all studies as a reference standard. We expect that our lead non-purine ultrapotent XO inhibitor will dose-dependently improve dP/dT, with an ED5O greater than 2-fold greater than allopurinol. PROPOSED COMMERCIAL APPLICATION: Sale of $500 million per annum are anticipated in the US alone, based upon an estimate of a 1% incidence of CHF in the general population (=2.5 million potential subjects), a 10% market penetration, and an annual expenditure per patient of $2,000. The worldwide market (developed countries only) is four times larger. Given the intoleerance for allopurinol in 10% of patients, and the current absence of a second-line medication, we expect the market acceptance of a safe and effective alternative XO inhibitor to be achieved rapidly over a five year period. We believe the high price point ($6 per day) is amply justified by the lack of an alternative to allopurinol. Estimated worldwide gross sales revenues after market entry and maturation (ca. 4 years after FDA approval) are expected to equal $1-2 billion per annum. 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
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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 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
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.3 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 heart failure, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “heart failure” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for heart failure (hyperlinks lead to article summaries): •
A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II. Author(s): Degenring FH, Suter A, Weber M, Saller R. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10(5): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833999&dopt=Abstract
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A randomised study of home-based electrical stimulation of the legs and conventional bicycle exercise training for patients with chronic heart failure. Author(s): Harris S, LeMaitre JP, Mackenzie G, Fox KA, Denvir MA. Source: European Heart Journal. 2003 May; 24(9): 871-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727155&dopt=Abstract
3
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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Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic heart failure. Author(s): Androne AS, Hryniewicz K, Goldsmith R, Arwady A, Katz SD. Source: Heart (British Cardiac Society). 2003 August; 89(8): 854-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860856&dopt=Abstract
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ACNPs' role in heart failure management. Author(s): Figueira M. Source: The Nurse Practitioner. 2003 July; 28(7 Pt 1): 57-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861099&dopt=Abstract
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Acute and chronic effects of flosequinan on resting and exercise haemodynamics in congestive heart failure. Author(s): Thomas P, O'Gorman DJ, Sheridan DJ. Source: British Journal of Clinical Pharmacology. 1993 December; 36(6): 539-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959270&dopt=Abstract
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Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. Author(s): Breithardt OA, Sinha AM, Schwammenthal E, Bidaoui N, Markus KU, Franke A, Stellbrink C. Source: Journal of the American College of Cardiology. 2003 March 5; 41(5): 765-70. Erratum In: J Am Coll Cardiol. 2003 May 21; 41(10): 1852. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628720&dopt=Abstract
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Airflow limitation and breathing strategy in congestive heart failure patients during exercise. Author(s): Schroeder CA, Balfe DL, Khan SS, Mohsenifar Z. Source: Respiration; International Review of Thoracic Diseases. 2003 March-April; 70(2): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740509&dopt=Abstract
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Aldosterone receptor antagonists in the treatment of heart failure. Author(s): Perkerson KA, Coleman CI, White CM. Source: Conn Med. 2003 August; 67(7): 397-400. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502862&dopt=Abstract
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Aldosteronism in heart failure: a proinflammatory/fibrogenic cardiac phenotype. Search for biomarkers and potential drug targets. Author(s): Weber KT, Gerling IC, Kiani MF, Guntaka RV, Sun Y, Ahokas RA, Postlethwaite AE, Warrington KJ. Source: Current Drug Targets. 2003 August; 4(6): 505-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866665&dopt=Abstract
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Alveolar-capillary membrane dysfunction in heart failure: evidence of a pathophysiologic role. Author(s): Guazzi M. Source: Chest. 2003 September; 124(3): 1090-102. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970042&dopt=Abstract
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An interesting echocardiographic study in patients with severe chronic heart failure. Author(s): Trovato GM, Carpinteri G. Source: Journal of Cardiac Failure. 1995 December; 1(5): 421; Author Reply 421-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836717&dopt=Abstract
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Anemia and congestive heart failure. Author(s): van der Meer P, van Gilst WH, van Veldhuisen DJ. Source: Circulation. 2003 August 12; 108(6): E41-2; Author Reply E41-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914016&dopt=Abstract
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Anemia and congestive heart failure. Author(s): Steinborn W, Ponikowski P, Anker S. Source: Circulation. 2003 August 12; 108(6): E41-2; Author Reply E41-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914015&dopt=Abstract
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Anemia and congestive heart failure. Author(s): Schroecksnadel K, Wirleitner B, Fuchs D. Source: Circulation. 2003 August 12; 108(6): E41-2; Author Reply E41-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912799&dopt=Abstract
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Angiotensin converting enzyme inhibitors and beta-blockers in African Americans with heart failure. Author(s): McCullough PA, Philbin EF, Spertus JA, Sandberg KR, Kaatz S. Source: Ethn Dis. 2003 Summer; 13(3): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894957&dopt=Abstract
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Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. Author(s): Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J, Kempf W, Schubert A, Schuler G, Hambrecht R. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 861-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957433&dopt=Abstract
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Antiremodeling effect of long-term exercise training in patients with stable chronic heart failure: results of the Exercise in Left Ventricular Dysfunction and Chronic Heart Failure (ELVD-CHF) Trial. Author(s): Giannuzzi P, Temporelli PL, Corra U, Tavazzi L; ELVD-CHF Study Group. Source: Circulation. 2003 August 5; 108(5): 554-9. Epub 2003 July 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860904&dopt=Abstract
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Aspirin and heart failure: square evidence meets a round patient. Author(s): Konstam MA. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 203-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937356&dopt=Abstract
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Aspirin-angiotensin-converting enzyme inhibitor coadministration and mortality in patients with heart failure: a dose-related adverse effect of aspirin. Author(s): Guazzi M, Brambilla R, Reina G, Tumminello G, Guazzi MD. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1574-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860580&dopt=Abstract
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Associations among processes and outcomes of care for Medicare nursing home residents with acute heart failure. Author(s): Hutt E, Frederickson E, Ecord M, Kramer AM. Source: Journal of the American Medical Directors Association. 2003 July-August; 4(4): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837140&dopt=Abstract
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Barriers to managing heart failure in primary care. Heart failure clinics provide crucial link between primary and secondary care. Author(s): Davis RC, Bhatia G, Sosin M, Stubley J. Source: Bmj (Clinical Research Ed.). 2003 April 19; 326(7394): 883. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702634&dopt=Abstract
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Barriers to managing heart failure in primary care. Previous study revealed other factors to be important in management. Author(s): Lambert MF, Watt IS. Source: Bmj (Clinical Research Ed.). 2003 April 19; 326(7394): 883. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705243&dopt=Abstract
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Beat-to-beat assessment of QT/RR interval ratio in severe heart failure and overt myocardial ischemia: a measure of electrical integrity in diseased hearts. Author(s): Faber TS, Grom A, Schopflin M, Brunner M, Bode C, Zehender M. Source: Pacing and Clinical Electrophysiology : Pace. 2003 April; 26(4 Pt 1): 836-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715843&dopt=Abstract
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Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study. Author(s): Maisel AS, McCord J, Nowak RM, Hollander JE, Wu AH, Duc P, Omland T, Storrow AB, Krishnaswamy P, Abraham WT, Clopton P, Steg G, Aumont MC, Westheim A, Knudsen CW, Perez A, Kamin R, Kazanegra R, Herrmann HC, McCullough PA; Breathing Not Properly Multinational Study Investigators. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2010-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798574&dopt=Abstract
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Benign mature cystic teratoma of the anterior mediastinum leading to heart failure: report of a case. Author(s): Ozergin U, Gormus N, Aribas OK, Durgut K, Yuksek T. Source: Surgery Today. 2003; 33(7): 518-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506996&dopt=Abstract
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Beta blockers in heart failure. Author(s): Dargie HJ. Source: Lancet. 2003 July 5; 362(9377): 2-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853188&dopt=Abstract
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Beta-blocker therapy and severe heart failure: myth or reality? Author(s): Ventura HO, Kalapura T. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 197-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937355&dopt=Abstract
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Beta-blockers and angiotensin-converting enzyme inhibitors/receptor blockers prescriptions after hospital discharge for heart failure are associated with decreased mortality in Alberta, Canada. Author(s): Johnson D, Jin Y, Quan H, Cujec B. Source: Journal of the American College of Cardiology. 2003 October 15; 42(8): 1438-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563589&dopt=Abstract
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Beta-blockers for heart failure: why, which, when, and where. Author(s): Cleland JG. Source: The Medical Clinics of North America. 2003 March; 87(2): 339-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693729&dopt=Abstract
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Beta-blockers in chronic heart failure: what have we learned? What do we still need to know? Author(s): Krum H. Source: Current Opinion in Pharmacology. 2003 April; 3(2): 168-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681239&dopt=Abstract
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Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Author(s): Reiken S, Wehrens XH, Vest JA, Barbone A, Klotz S, Mancini D, Burkhoff D, Marks AR. Source: Circulation. 2003 May 20; 107(19): 2459-66. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743001&dopt=Abstract
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Biological variation for N-terminal pro- and B-type natriuretic peptides and implications for therapeutic monitoring of patients with congestive heart failure. Author(s): Wu AH, Smith A, Wieczorek S, Mather JF, Duncan B, White CM, McGill C, Katten D, Heller G. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 628-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943894&dopt=Abstract
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Biventricular pacing for heart failure. Author(s): Lane RE, Mayet J, Peters NS. Source: Bmj (Clinical Research Ed.). 2003 May 3; 326(7396): 944-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727739&dopt=Abstract
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Biventricular pacing in heart failure: back to basics in the pathophysiology of left bundle branch block to reduce the number of nonresponders. Author(s): Ansalone G, Giannantoni P, Ricci R, Trambaiolo P, Fedele F, Santini M. Source: The American Journal of Cardiology. 2003 May 8; 91(9A): 55F-61F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729851&dopt=Abstract
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Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. Author(s): Lainchbury JG, Campbell E, Frampton CM, Yandle TG, Nicholls MG, Richards AM. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 728-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932611&dopt=Abstract
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Brain natriuretic peptide facilitates severity classification of stable chronic heart failure with left ventricular dysfunction. Author(s): Sakurai S, Adachi H, Hasegawa A, Hoshizaki H, Oshima S, Taniguchi K, Kurabayashi M. Source: Heart (British Cardiac Society). 2003 June; 89(6): 661-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748228&dopt=Abstract
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Brain natriuretic peptide in diagnosis and treatment of heart failure. Author(s): Bhatia V, Nayyar P, Dhindsa S. Source: Journal of Postgraduate Medicine. 2003 April-June; 49(2): 182-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867703&dopt=Abstract
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B-type natriuretic Peptide predicts clinical presentations and ventricular overloading in patients with heart failure. Author(s): Joung BY, Park BE, Kim DS, Hong BK, Kim DY, Cho YH, Lee SH, Yoon YW, Kim HS, Kim JH, Kwon HM. Source: Yonsei Medical Journal. 2003 August 30; 44(4): 623-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950118&dopt=Abstract
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B-type natriuretic peptide testing in a nurse-led heart failure clinic. Author(s): Coady E. Source: Nurs Times. 2003 July 8-14; 99(27): 44-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882056&dopt=Abstract
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B-type natriuretic peptides. A diagnostic breakthrough in heart failure. Author(s): McCullough PA. Source: Minerva Cardioangiol. 2003 April; 51(2): 121-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783068&dopt=Abstract
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Candesartan and heart failure: the allure of CHARM. Author(s): White HD. Source: Lancet. 2003 September 6; 362(9386): 754-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678864&dopt=Abstract
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Cardiac resynchronisation therapy--new treatment for heart failure. Author(s): Ng KS. Source: Singapore Med J. 2003 March; 44(3): 109-11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953721&dopt=Abstract
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Cardiac resynchronization therapy for heart failure shows great promise. Author(s): Ovsyshcher IE, Auricchio A. Source: Isr Med Assoc J. 2003 August; 5(8): 589-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929300&dopt=Abstract
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Cardiac resynchronization therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias. Author(s): Higgins SL, Hummel JD, Niazi IK, Giudici MC, Worley SJ, Saxon LA, Boehmer JP, Higginbotham MB, De Marco T, Foster E, Yong PG. Source: Journal of the American College of Cardiology. 2003 October 15; 42(8): 1454-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563591&dopt=Abstract
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Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. Author(s): Adamson PB, Kleckner KJ, VanHout WL, Srinivasan S, Abraham WT. Source: Circulation. 2003 July 22; 108(3): 266-9. Epub 2003 Jul 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860899&dopt=Abstract
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Changes over 6-months in health-related quality of life in a matched sample of Hispanics and non-Hispanics with heart failure. Author(s): Riegel B, Carlson B, Glaser D, Romero T. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2003 September; 12(6): 689-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516178&dopt=Abstract
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Cholinergic stimulation with pyridostigmine reduces ventricular arrhythmia and enhances heart rate variability in heart failure. Author(s): Behling A, Moraes RS, Rohde LE, Ferlin EL, Nobrega AC, Ribeiro JP. Source: American Heart Journal. 2003 September; 146(3): 494-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947369&dopt=Abstract
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Choosing metoprolol or carvedilol in heart failure (a pre-COMET commentary). Author(s): Rajput FS, Gnanasekeram H, Satwani S, Davenport JD, Gracely EJ, Gopalan R, Narula J. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 218-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860230&dopt=Abstract
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Colloid osmotic pressure: an under-recognized factor in the clinical syndrome of heart failure. Author(s): Konstam MA. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 717-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932608&dopt=Abstract
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Colour tissue velocity imaging can show resynchronisation of longitudinal left ventricular contraction pattern by biventricular pacing in patients with severe heart failure. Author(s): Schuster P, Faerestrand S, Ohm OJ. Source: Heart (British Cardiac Society). 2003 August; 89(8): 859-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860858&dopt=Abstract
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Combination of B-type natriuretic peptide and peak oxygen consumption improves risk stratification in outpatients with chronic heart failure. Author(s): Isnard R, Pousset F, Chafirovskaia O, Carayon A, Hulot JS, Thomas D, Komajda M. Source: American Heart Journal. 2003 October; 146(4): 729-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564330&dopt=Abstract
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Combining low-intensity and maximal exercise test results improves prognostic prediction in chronic heart failure. Author(s): Rickli H, Kiowski W, Brehm M, Weilenmann D, Schalcher C, Bernheim A, Oechslin E, Brunner-La Rocca HP. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849670&dopt=Abstract
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Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Author(s): Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A; Carvedilol Or Metoprolol European Trial Investigators. Source: Lancet. 2003 July 5; 362(9377): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853193&dopt=Abstract
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Congestive heart failure and depression in older adults: clinical course and health services use 6 months after hospitalization. Author(s): Fulop G, Strain JJ, Stettin G. Source: Psychosomatics. 2003 September-October; 44(5): 367-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954910&dopt=Abstract
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Congestive heart failure and the growth hormone/insulin-like growth factor-1 (GH/IGF-1) system. Author(s): Dreifuss P. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 245-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860243&dopt=Abstract
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Congestive heart failure due to traumatic arteriovenous fistula--two case reports. Author(s): Cakmak M, Cakmak N, Arikan E, Sert A, Say AE, Ersek B. Source: Angiology. 2003 September-October; 54(5): 625-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14565641&dopt=Abstract
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Congestive heart failure: guidelines for the primary care physician. Author(s): Galin I, Barann DA. Source: The Mount Sinai Journal of Medicine, New York. 2003 September; 70(4): 251-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968198&dopt=Abstract
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Continuous positive airway pressure in patients with heart failure. Author(s): Weinstein MD. Source: The New England Journal of Medicine. 2003 July 3; 349(1): 93-5; Author Reply 93-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846230&dopt=Abstract
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Current presentation and management of heart failure in cardiology and internal medicine hospital units: a tale of two worlds--the TEMISTOCLE study. Author(s): Di Lenarda A, Scherillo M, Maggioni AP, Acquarone N, Ambrosio GB, Annicchiarico M, Bellis P, Bellotti P, De Maria R, Lavecchia R, Lucci D, Mathieu G, Opasich C, Porcu M, Tavazzi L, Cafiero M; TEMISTOCLE Investigators. Source: American Heart Journal. 2003 October; 146(4): E12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564335&dopt=Abstract
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Cyclic GMP production by ANP, BNP, and NO during worsening and improvement of chronic heart failure. Author(s): Takahashi M, Takeda S, Kurokawa S, Kubo T, Fukuda N, Izumi T. Source: Japanese Heart Journal. 2003 September; 44(5): 713-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587653&dopt=Abstract
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Decompensated heart failure revisited. Author(s): Ghali JK. Source: The American Journal of Medicine. 2003 June 1; 114(8): 695-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798459&dopt=Abstract
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Delivering the cumulative benefits of triple therapy to improve outcomes in heart failure: too many cooks will spoil the broth. Author(s): Cleland JG, Clark AL. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1234-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522487&dopt=Abstract
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Demographics and concomitant disorders in heart failure. Author(s): Krum H, Gilbert RE. Source: Lancet. 2003 July 12; 362(9378): 147-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867118&dopt=Abstract
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Depression and congestive heart failure. Author(s): Guck TP, Elsasser GN, Kavan MG, Barone EJ. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 May-June; 9(3): 163-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826775&dopt=Abstract
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Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality. Author(s): Kittleson M, Hurwitz S, Shah MR, Nohria A, Lewis E, Givertz M, Fang J, Jarcho J, Mudge G, Stevenson LW. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 2029-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798577&dopt=Abstract
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Diabetes and heart failure: is insulin therapy the answer? Author(s): Levy WC, Hirsch IB. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 1051-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678929&dopt=Abstract
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Diabetes mellitus and heart failure. Author(s): Jagasia D, McNulty PH. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 May-June; 9(3): 133-9; Quiz 140-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826771&dopt=Abstract
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Diagnosis and treatment of heart failure in primary health care among elderly patients with non-insulin-dependent diabetes mellitus, with special reference to use of echocardiography. Author(s): Halling A, Berglund J. Source: Scandinavian Journal of Primary Health Care. 2003 June; 21(2): 96-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877372&dopt=Abstract
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Diastolic heart failure demystified. Author(s): Andrew P. Source: Chest. 2003 August; 124(2): 744-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907569&dopt=Abstract
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Dietary intake of various nutrients in older patients with congestive heart failure. Author(s): Gorelik O, Almoznino-Sarafian D, Feder I, Wachsman O, Alon I, Litvinjuk V, Roshovsky M, Modai D, Cohen N. Source: Cardiology. 2003; 99(4): 177-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845243&dopt=Abstract
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Dietary research in heart failure: beyond the salt shaker. Author(s): Silver MA. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1224-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522485&dopt=Abstract
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Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Author(s): McCrohon JA, Moon JC, Prasad SK, McKenna WJ, Lorenz CH, Coats AJ, Pennell DJ. Source: Circulation. 2003 July 8; 108(1): 54-9. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821550&dopt=Abstract
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Digoxin in heart failure and cardiac arrhythmias. Author(s): Campbell TJ, MacDonald PS. Source: The Medical Journal of Australia. 2003 July 21; 179(2): 98-102. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864722&dopt=Abstract
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Digoxin therapy and the risk of primary cardiac arrest in patients with congestive heart failure: effect of mild-moderate renal impairment. Author(s): Rea TD, Siscovick DS, Psaty BM, Pearce RM, Raghunathan TE, Whitsel EA, Cobb LA, Weinmann S, Anderson GD, Arbogast P, Lin D. Source: Journal of Clinical Epidemiology. 2003 July; 56(7): 646-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921933&dopt=Abstract
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Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). Author(s): Domanski M, Norman J, Pitt B, Haigney M, Hanlon S, Peyster E; Studies of Left Ventricular Dysfunction. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 705-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932605&dopt=Abstract
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Diverse populations, new techniques: non-surgical advances in heart failure 2003. Author(s): Mehra MR, Uber PA. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937352&dopt=Abstract
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Do antiarrhythmics prevent sudden death in patients with heart failure? Author(s): Ball TA, Kerns JW, Nashelsky J. Source: The Journal of Family Practice. 2003 September; 52(9): 719-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967547&dopt=Abstract
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Do thiazolidinediones cause congestive heart failure? Author(s): Kennedy FP. Source: Mayo Clinic Proceedings. 2003 September; 78(9): 1076-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962160&dopt=Abstract
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Does race matter in heart failure? Author(s): Yancy CW. Source: American Heart Journal. 2003 August; 146(2): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891183&dopt=Abstract
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Doppler-echocardiographic indices of diastolic function in heart failure admissions with preserved left ventricular systolic function. Author(s): Cahill JM, Horan M, Quigley P, Maurer B, McDonald K. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 August; 4(4): 473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167386&dopt=Abstract
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Echocardiographic features of patients with heart failure who may benefit from biventricular pacing. Author(s): Makaryus AN, Arduini AD, Mallin J, Chung E, Kort S, Shi Q, Jadonath R, Mangion J. Source: Echocardiography (Mount Kisco, N.Y.). 2003 April; 20(3): 217-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848658&dopt=Abstract
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Economic implications of nesiritide versus dobutamine in the treatment of patients with acutely decompensated congestive heart failure. Author(s): de Lissovoy G, Stier DM, Ciesla G, Munger M, Burger AJ. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 631-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943895&dopt=Abstract
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Effect of beta blockade (carvedilol or metoprolol) on activation of the reninangiotensin-aldosterone system and natriuretic peptides in chronic heart failure. Author(s): Fung JW, Yu CM, Yip G, Chan S, Yandle TG, Richards AM, Nicholls MG, Sanderson JE. Source: The American Journal of Cardiology. 2003 August 15; 92(4): 406-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914870&dopt=Abstract
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Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure. Author(s): Maiolino G, Rossi GP. Source: Circulation. 2003 October 14; 108(15): E112; Author Reply E112. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557350&dopt=Abstract
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Effectiveness of the clinical pathway in the management of congestive heart failure. Author(s): Ranjan A, Tarigopula L, Srivastava RK, Obasanjo OO, Obah E. Source: Southern Medical Journal. 2003 July; 96(7): 661-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940315&dopt=Abstract
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Effects of candesartan in patients with chronic heart failure and preserved leftventricular ejection fraction: the CHARM-Preserved Trial. Author(s): Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J; CHARM Investigators and Committees. Source: Lancet. 2003 September 6; 362(9386): 777-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678871&dopt=Abstract
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Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Author(s): Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, Pfeffer MA, Swedberg K; CHARM Investigators and Committees. Source: Lancet. 2003 September 6; 362(9386): 772-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678870&dopt=Abstract
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Effects of candesartan in patients with chronic heart failure and reduced leftventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Author(s): McMurray JJ, Ostergren J, Swedberg K, Granger CB, Held P, Michelson EL, Olofsson B, Yusuf S, Pfeffer MA; CHARM Investigators and Committees. Source: Lancet. 2003 September 6; 362(9386): 767-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678869&dopt=Abstract
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Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Author(s): Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators and Committees. Source: Lancet. 2003 September 6; 362(9386): 759-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678868&dopt=Abstract
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Effects of clopidogrel and aspirin combination versus aspirin alone on platelet aggregation and major receptor expression in patients with heart failure: the Plavix Use for Treatment Of Congestive Heart Failure (PLUTO-CHF) trial. Author(s): Serebruany VL, Malinin AI, Jerome SD, Lowry DR, Morgan AW, Sane DC, Tanguay JF, Steinhubl SR, O'connor CM. Source: American Heart Journal. 2003 October; 146(4): 713-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564328&dopt=Abstract
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Effects of cold exposure on submaximal exercise performance and adrenergic activation in patients with congestive heart failure and the effects of beta-adrenergic blockade (carvedilol or metoprolol). Author(s): Blanchet M, Ducharme A, Racine N, Rouleau JL, Tardif JC, Juneau M, Marquis J, Larivee L, Nigam A, Fortier A, White M. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 548-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943875&dopt=Abstract
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Effects of spironolactone and metoprolol on QT dispersion in heart failure. Author(s): Akbulut M, Ozbay Y, Ilkay E, Karaca I, Arslan N. Source: Japanese Heart Journal. 2003 September; 44(5): 681-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587650&dopt=Abstract
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Effects of two Gbetagamma-binding proteins--N-terminally truncated phosducin and beta-adrenergic receptor kinase C terminus (betaARKct)--in heart failure. Author(s): Li Z, Laugwitz KL, Pinkernell K, Pragst I, Baumgartner C, Hoffmann E, Rosport K, Munch G, Moretti A, Humrich J, Lohse MJ, Ungerer M. Source: Gene Therapy. 2003 August; 10(16): 1354-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883532&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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Electrical remodeling of the atria in congestive heart failure: electrophysiological and electroanatomic mapping in humans. Author(s): Sanders P, Morton JB, Davidson NC, Spence SJ, Vohra JK, Sparks PB, Kalman JM. Source: Circulation. 2003 September 23; 108(12): 1461-8. Epub 2003 Sep 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952837&dopt=Abstract
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Epidemiology, pathophysiology, prognosis, and treatment of systolic and diastolic heart failure in elderly patients. Author(s): Aronow WS. Source: Heart Disease. 2003 July-August; 5(4): 279-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877761&dopt=Abstract
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Evaluation and management of a patient with congestive heart failure. Author(s): Walsh MN, Tavel ME. Source: Chest. 2003 August; 124(2): 728-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907565&dopt=Abstract
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Evolving rationale for angiotensin-converting enzyme inhibition in chronic heart failure. Author(s): Banerjee A, Talreja A, Sonnenblick EH, LeJemtel TH. Source: The Mount Sinai Journal of Medicine, New York. 2003 September; 70(4): 225-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968195&dopt=Abstract
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Exercise testing in heart failure: maximal, submaximal, or both? Author(s): Bittner V. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 123-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849671&dopt=Abstract
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Exercise training and skeletal muscle inflammation in chronic heart failure: feeling better about fatigue. Author(s): Mann DL, Reid MB. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 869-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957434&dopt=Abstract
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Factors influencing the length of hospital stay of patients with heart failure. Author(s): Wright SP, Verouhis D, Gamble G, Swedberg K, Sharpe N, Doughty RN. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 March; 5(2): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12644013&dopt=Abstract
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Failure of platelet parameters and biomarkers to correlate platelet function to severity and etiology of heart failure in patients enrolled in the EPCOT trial. With special reference to the Hemodyne hemostatic analyzer. Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure. Author(s): Serebruany VL, McKenzie ME, Meister AF, Fuzaylov SY, Gurbel PA, Atar D, Gattis WA, O'Connor CM. Source: Pathophysiology of Haemostasis and Thrombosis. 2002 January-February; 32(1): 8-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214158&dopt=Abstract
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Familial cardiomyopathies: significant causes of heart failure. Author(s): Crispell KA. Source: Current Cardiology Reports. 2003 May; 5(3): 187-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691634&dopt=Abstract
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Families dealing with advanced heart failure: a challenge and an opportunity. Author(s): Callahan HE. Source: Critical Care Nursing Quarterly. 2003 July-September; 26(3): 230-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930039&dopt=Abstract
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Family caregivers need support with heart failure patients. Author(s): Saunders MM. Source: Holistic Nursing Practice. 2003 May-June; 17(3): 136-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784897&dopt=Abstract
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Fatigued elderly patients with chronic heart failure: do patient reports and nurse recordings correspond? Author(s): Ekman I, Ehrenberg A. Source: International Journal of Nursing Terminologies and Classifications : the Official Journal of Nanda International. 2002 October-December; 13(4): 127-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629682&dopt=Abstract
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Feedback inhibition of catecholamine release by two different alpha2-adrenoceptor subtypes prevents progression of heart failure. Author(s): Brede M, Wiesmann F, Jahns R, Hadamek K, Arnolt C, Neubauer S, Lohse MJ, Hein L. Source: Circulation. 2002 November 5; 106(19): 2491-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417548&dopt=Abstract
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Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure. Author(s): Tang WH, Francis GS, Hoogwerf BJ, Young JB. Source: Journal of the American College of Cardiology. 2003 April 16; 41(8): 1394-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706937&dopt=Abstract
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For the patient. New treatments for heart failure in Black people. Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity. Author(s): Ajayi AA, Sofowora GG, Adigun AQ, Asiyanbola B. Source: Ethn Dis. 2003 Winter; 13(1): 150. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723027&dopt=Abstract
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Frailty is a strong modulator of heart failure-associated mortality. Author(s): Rozzini R, Sabatini T, Frisoni GB, Trabucchi M. Source: Archives of Internal Medicine. 2003 March 24; 163(6): 737-8; Author Reply 738. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639210&dopt=Abstract
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Frequency of aspirin resistance in patients with congestive heart failure treated with antecedent aspirin. Author(s): Sane DC, McKee SA, Malinin AI, Serebruany VL. Source: The American Journal of Cardiology. 2002 October 15; 90(8): 893-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372584&dopt=Abstract
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Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials. Author(s): Hasdai D, Topol EJ, Kilaru R, Battler A, Harrington RA, Vahanian A, Ohman EM, Granger CB, Van de Werf F, Simoons ML, O'connor CM, Holmes DR Jr. Source: American Heart Journal. 2003 January; 145(1): 73-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514657&dopt=Abstract
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From mouse to man: understanding heart failure through genetically altered mouse models. Author(s): Chu G, Haghighi K, Kranias EG. Source: Journal of Cardiac Failure. 2002 December; 8(6 Suppl): S432-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555156&dopt=Abstract
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Frontiers in congestive heart failure: pseudonormal mitral filling pattern predicts hospital re-admission in patients with congestive heart failure. Author(s): Tepper D. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 July-August; 8(4): 236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147950&dopt=Abstract
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Functional and echocardiographic improvement following multisite biventricular pacing for congestive heart failure. Author(s): Chan KL, Tang AS, Achilli A, Sassara M, Bocchiardo M, Gaita F, Cavaglia S, Hilpisch K, Hill MR, Gras D. Source: The Canadian Journal of Cardiology. 2003 March 31; 19(4): 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704484&dopt=Abstract
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Functional class in patients with heart failure is associated with the development of diabetes. Author(s): Bell DS. Source: The American Journal of Medicine. 2003 October 1; 115(5): 412; Author Reply 412. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14553881&dopt=Abstract
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Functional class in patients with heart failure is associated with the development of diabetes. Author(s): Tenenbaum A, Motro M, Fisman EZ, Leor J, Freimark D, Boyko V, Mandelzweig L, Adler Y, Sherer Y, Behar S. Source: The American Journal of Medicine. 2003 March; 114(4): 271-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681453&dopt=Abstract
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Functional consequence of serotonin/5-HT2B receptor signaling in heart: role of mitochondria in transition between hypertrophy and heart failure? Author(s): Nebigil CG, Maroteaux L. Source: Circulation. 2003 August 19; 108(7): 902-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925446&dopt=Abstract
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Furosemide challenge in patients with heart failure and adverse reactions to sulfacontaining diuretics. Author(s): Earl G, Davenport J, Narula J. Source: Annals of Internal Medicine. 2003 February 18; 138(4): 358-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585844&dopt=Abstract
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Future challenges in quality improvement in heart failure. Author(s): Havranek EP, Masoudi FA, Ralston DL, Susman NJ, Krumholz HM, Taylor JP. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 November-December; 8(6): 342-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461325&dopt=Abstract
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Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing beta-blocker therapy. Author(s): Bello D, Shah DJ, Farah GM, Di Luzio S, Parker M, Johnson MR, Cotts WG, Klocke FJ, Bonow RO, Judd RM, Gheorghiade M, Kim RJ. Source: Circulation. 2003 October 21; 108(16): 1945-53. Epub 2003 Oct 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557364&dopt=Abstract
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Gaining weight increases the risk for the development of heart failure. Author(s): Basile J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2002 NovemberDecember; 4(6): 433. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461308&dopt=Abstract
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Gap junction remodeling in heart failure. Author(s): Severs NJ. Source: Journal of Cardiac Failure. 2002 December; 8(6 Suppl): S293-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555135&dopt=Abstract
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Gender differences in quality of life are minimal in patients with heart failure. Author(s): Riegel B, Moser DK, Carlson B, Deaton C, Armola R, Sethares K, Shively M, Evangelista L, Albert N. Source: Journal of Cardiac Failure. 2003 February; 9(1): 42-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612872&dopt=Abstract
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Gender, age, and heart failure with preserved left ventricular systolic function. Author(s): Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, Krumholz HM. Source: Journal of the American College of Cardiology. 2003 January 15; 41(2): 217-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535812&dopt=Abstract
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Gene transfer of beta-adrenergic signaling components for heart failure. Author(s): Koch WJ. Source: Journal of Cardiac Failure. 2002 December; 8(6 Suppl): S526-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555169&dopt=Abstract
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Genetics in heart failure: practical incorporation of this new biologic dimension. Author(s): Donahue M, Kraus W, Granger C. Source: American Heart Journal. 2002 December; 144(6): 938-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486417&dopt=Abstract
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Ghrelin improves left ventricular dysfunction and cardiac cachexia in heart failure. Author(s): Nagaya N, Kangawa K. Source: Current Opinion in Pharmacology. 2003 April; 3(2): 146-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681236&dopt=Abstract
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Giant cell myocarditis presenting as rapidly progressive congestive heart failure complicated by ventricular arrhythmias. Author(s): Greer RW, Taggart MW, Sartin BW, Angelica NJ, Johnson GM, Pappas ND, Newman WP 3rd, Glancy DL. Source: J La State Med Soc. 2003 July-August; 155(4): 198-202; Quiz 202. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506826&dopt=Abstract
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Glitazones and heart failure: critical appraisal for the clinician. Author(s): Buse JB. Source: Circulation. 2003 August 26; 108(8): E57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939247&dopt=Abstract
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Glitazones and heart failure: critical appraisal for the clinician. Author(s): Wang CH, Weisel RD, Liu PP, Fedak PW, Verma S. Source: Circulation. 2003 March 18; 107(10): 1350-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642352&dopt=Abstract
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G-protein-coupled receptor function in heart failure. Author(s): Prasad SV, Nienaber J, Rockman HA. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 439-44. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858569&dopt=Abstract
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Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy. Author(s): Adamopoulos S, Parissis JT, Georgiadis M, Karatzas D, Paraskevaidis J, Kroupis C, Karavolias G, Koniavitou K, Kremastinos DT. Source: American Heart Journal. 2002 August; 144(2): 359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177657&dopt=Abstract
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Growth hormone resistance in chronic heart failure and its therapeutic implications. Author(s): Cicoira M, Kalra PR, Anker SD. Source: Journal of Cardiac Failure. 2003 June; 9(3): 219-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815572&dopt=Abstract
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Growth hormone therapy in heart failure: where are we now? Author(s): Demers C, McKelvie RS. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 March-April; 9(2): 84-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671339&dopt=Abstract
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Hallmarks of ion channel gene expression in end-stage heart failure. Author(s): Borlak J, Thum T. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 September; 17(12): 1592-608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958166&dopt=Abstract
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Heart failure and treatment: part II. Perianesthesia management. Author(s): Gilmore JC. Source: Journal of Perianesthesia Nursing : Official Journal of the American Society of Perianesthesia Nurses / American Society of Perianesthesia Nurses. 2003 August; 18(4): 242-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923751&dopt=Abstract
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Heart failure diagnosis in primary health care: clinical characteristics of problematic patients. A clinical judgement analysis study. Author(s): Skaner Y, Bring J, Ullman B, Strender LE. Source: Bmc Family Practice [electronic Resource]. 2003 September 18; 4(1): 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14498999&dopt=Abstract
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Heart failure management: caregiver versus care plan. Author(s): Kim DH, Hunt SA. Source: Circulation. 2003 July 15; 108(2): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860891&dopt=Abstract
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Heart failure. Author(s): Schoevaerdts D, Swine C, Vanpee D. Source: The New England Journal of Medicine. 2003 September 4; 349(10): 1002-4; Author Reply 1002-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959102&dopt=Abstract
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Heart failure. Author(s): Silver SM. Source: The New England Journal of Medicine. 2003 September 4; 349(10): 1002-4; Author Reply 1002-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959101&dopt=Abstract
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Heart failure. Author(s): Rodriguez W. Source: The New England Journal of Medicine. 2003 September 4; 349(10): 1002-4; Author Reply 1002-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959100&dopt=Abstract
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Heart failure. Author(s): Eltzschig HK, Ehlers R, Shernan SK. Source: The New England Journal of Medicine. 2003 September 4; 349(10): 1002-4; Author Reply 1002-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954753&dopt=Abstract
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Heart failure: how big is the problem? Who are the patients? What does the future hold? Author(s): Ansari M, Massie BM. Source: American Heart Journal. 2003 July; 146(1): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851600&dopt=Abstract
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Heart failure: treatment and ethnic origin. Author(s): Sosin MD, Bhatia GS, Davis RC, Connolly DL, Lip GY. Source: Lancet. 2003 September 13; 362(9387): 919-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678991&dopt=Abstract
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Heart failure: treatment and ethnic origin. Author(s): McKenzie DB, Wilcox RG. Source: Lancet. 2003 September 13; 362(9387): 919. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678990&dopt=Abstract
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Heart rate variability in chronic heart failure: target for therapy? Author(s): Sueta CA. Source: American Heart Journal. 2003 September; 146(3): 385-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947353&dopt=Abstract
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Heart rate variability in heart failure. Author(s): Musialik-Lydka A, Sredniawa B, Pasyk S. Source: Kardiol Pol. 2003 January; 58(1): 10-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502297&dopt=Abstract
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Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. Author(s): Torre-Amione G, Young JB, Colucci WS, Lewis BS, Pratt C, Cotter G, Stangl K, Elkayam U, Teerlink JR, Frey A, Rainisio M, Kobrin I. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 140-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849674&dopt=Abstract
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High output heart failure 8 months after an acquired arteriovenous fistula. Author(s): Durakoglugil ME, Kaya MG, Boyaci B, Cengel A. Source: Japanese Heart Journal. 2003 September; 44(5): 805-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587663&dopt=Abstract
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Historical vignettes in heart failure: history of heart failure. Author(s): Ventura HO. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937354&dopt=Abstract
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Hormone replacement therapy is associated with improved survival in women with advanced heart failure. Author(s): Lindenfeld J, Ghali JK, Krause-Steinrauf HJ, Khan S, Adams K, Goldman S, Peberdy MA, Yancy C, Thaneemit-Chen S, Larsen RL, Young J, Lowes B, Rosenberg YD; BEST Investigators. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1238-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522488&dopt=Abstract
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Hyperkalemia, congestive heart failure, and aldosterone receptor antagonism. Author(s): Sica DA, Gehr TW, Yancy C. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 224-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937359&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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Hypoalbuminemia in elderly patients with acute diastolic heart failure. Author(s): Arques S, Ambrosi P, Gelisse R, Luccioni R, Habib G. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 712-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932607&dopt=Abstract
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Identification of factors predictive of hospital readmissions for patients with heart failure. Author(s): Schwarz KA, Elman CS. Source: Heart & Lung : the Journal of Critical Care. 2003 March-April; 32(2): 88-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734531&dopt=Abstract
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Immediate- vs extended-release metoprolol in heart failure. Author(s): Huneycutt B. Source: The Journal of Family Practice. 2003 August; 52(8): 635-6; Author Reply 636. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899820&dopt=Abstract
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Impact of a home communication intervention for coronary artery bypass graft patients with ischemic heart failure on self-efficacy, coronary disease risk factor modification, and functioning. Author(s): Barnason S, Zimmerman L, Nieveen J, Schmaderer M, Carranza B, Reilly S. Source: Heart & Lung : the Journal of Critical Care. 2003 May-June; 32(3): 147-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827099&dopt=Abstract
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Implication of cardiac remodeling in heart failure: mechanisms and therapeutic strategies. Author(s): Takano H, Hasegawa H, Nagai T, Komuro I. Source: Intern Med. 2003 June; 42(6): 465-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857042&dopt=Abstract
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Incidence and risk factors of asymptomatic first-dose hypotension with angiotensinconverting enzyme inhibitors in chronic heart failure due to systolic dysfunction. Author(s): Thanikachalam S, Manchanda SC. Source: Indian Heart J. 2003 March-April; 55(2): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921333&dopt=Abstract
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Incident cases of heart failure in a community cohort: importance and outcomes of patients with preserved systolic function. Author(s): Ansari M, Alexander M, Tutar A, Massie BM. Source: American Heart Journal. 2003 July; 146(1): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851618&dopt=Abstract
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Increased distance between mitral valve coaptation point and mitral annular plane: significance and correlations in patients with heart failure. Author(s): Karagiannis SE, Karatasakis GT, Koutsogiannis N, Athanasopoulos GD, Cokkinos DV. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1174-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975411&dopt=Abstract
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Increased myocardial apoptosis in patients with unfavorable left ventricular remodeling and early symptomatic post-infarction heart failure. Author(s): Abbate A, Biondi-Zoccai GG, Bussani R, Dobrina A, Camilot D, Feroce F, Rossiello R, Baldi F, Silvestri F, Biasucci LM, Baldi A. Source: Journal of the American College of Cardiology. 2003 March 5; 41(5): 753-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12628718&dopt=Abstract
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Increased myocardial NADPH oxidase activity in human heart failure. Author(s): Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, Shah AM. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2164-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821241&dopt=Abstract
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Increased urinary 15-F2t-isoprostane concentrations in patients with non-ischaemic congestive heart failure: a marker of oxidative stress. Author(s): Nonaka-Sarukawa M, Yamamoto K, Aoki H, Takano H, Katsuki T, Ikeda U, Shimada K. Source: Heart (British Cardiac Society). 2003 August; 89(8): 871-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860861&dopt=Abstract
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Influence of Cheyne-Stokes respiration on cardiovascular oscillations in heart failure. Author(s): Leung RS, Floras JS, Lorenzi-Filho G, Rankin F, Picton P, Bradley TD. Source: American Journal of Respiratory and Critical Care Medicine. 2003 June 1; 167(11): 1534-9. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626347&dopt=Abstract
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Inhibitory cardiac transcription factor, SRF-N, is generated by caspase 3 cleavage in human heart failure and attenuated by ventricular unloading. Author(s): Chang J, Wei L, Otani T, Youker KA, Entman ML, Schwartz RJ. Source: Circulation. 2003 July 29; 108(4): 407-13. Epub 2003 Jul 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874181&dopt=Abstract
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Injecting some hope. Cell therapy could lead to new treatments for congestive heart failure, whose sufferers now have few options. Author(s): Becker C. Source: Modern Healthcare. 2003 August 11; 33(32): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931539&dopt=Abstract
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Insulin ameliorates exercise ventilatory efficiency and oxygen uptake in patients with heart failure-type 2 diabetes comorbidity. Author(s): Guazzi M, Tumminello G, Matturri M, Guazzi MD. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 104450. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678928&dopt=Abstract
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Is beta-blockade useful in heart failure patients with atrial fibrillation? An analysis of data from two previously completed prospective trials. Author(s): Fung JW, Chan SK, Yeung LY, Sanderson JE. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 August; 4(4): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167389&dopt=Abstract
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Is depressed myocyte contractility centrally involved in heart failure? Author(s): Houser SR, Margulies KB. Source: Circulation Research. 2003 March 7; 92(4): 350-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623873&dopt=Abstract
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Is diastolic heart failure synonymous with heart failure with preserved ejection fraction? Author(s): Kessler KM. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1335; Author Reply 1335-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522506&dopt=Abstract
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Is heart failure in African Americans a distinct entity? Author(s): Scott RL. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 193-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937353&dopt=Abstract
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Is heart failure survival improving? Evidence from 2323 elderly patients hospitalized between 1989-2000. Author(s): Feinglass J, Martin GJ, Lin E, Johnson MR, Gheorghiade M. Source: American Heart Journal. 2003 July; 146(1): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851617&dopt=Abstract
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Is nutritional intake adequate in chronic heart failure patients? Author(s): Aquilani R, Opasich C, Verri M, Boschi F, Febo O, Pasini E, Pastoris O. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1218-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522484&dopt=Abstract
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Kinases as therapeutic targets for heart failure. Author(s): Vlahos CJ, McDowell SA, Clerk A. Source: Nature Reviews. Drug Discovery. 2003 February; 2(2): 99-113. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563301&dopt=Abstract
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Late breaking heart failure trials from the 2003 ACC meeting: EPHESUS and COMPANION. Author(s): Teerlink JR, Massie BM; EPHESUS and COMPANION. Source: Journal of Cardiac Failure. 2003 June; 9(3): 158-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815564&dopt=Abstract
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Learning needs of patients with congestive heart failure. Author(s): Chan AD, Reid GJ, Farvolden P, Deane ML, Bisaillon S. Source: The Canadian Journal of Cardiology. 2003 March 31; 19(4): 413-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704489&dopt=Abstract
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Left ventricular assist devices as permanent heart failure therapy: the price of progress. Author(s): Oz MC, Gelijns AC, Miller L, Wang C, Nickens P, Arons R, Aaronson K, Richenbacher W, van Meter C, Nelson K, Weinberg A, Watson J, Rose EA, Moskowitz AJ. Source: Annals of Surgery. 2003 October; 238(4): 577-83; Discussion 583-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530729&dopt=Abstract
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Left ventricular ejection fraction and volumes from gated blood-pool SPECT: comparison with planar gated blood-pool imaging and assessment of repeatability in patients with heart failure. Author(s): Wright GA, Thackray S, Howey S, Cleland JG. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 April; 44(4): 494-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679390&dopt=Abstract
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Left ventricular hypertrophy and heart failure in women. Author(s): Agabiti-Rosei E, Muiesan ML. Source: Journal of Hypertension. 2002 May; 20 Suppl 2: S34-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183849&dopt=Abstract
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Levosimendan: a new dual-action drug in the treatment of acute heart failure. Author(s): Mebazaa A, Erhardt L. Source: Int J Clin Pract. 2003 June; 57(5): 410-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846347&dopt=Abstract
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Limitations of current medical therapies for the treatment of heart failure. Author(s): Miller LW. Source: Reviews in Cardiovascular Medicine. 2003; 4 Suppl 2: S21-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776010&dopt=Abstract
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Limitations of the use of clinical trial results in managing heart failure in the AfricanAmerican community: a time for active participation in generating applicable data. Author(s): Franciosa JA. Source: Journal of the National Medical Association. 2003 January; 95(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656445&dopt=Abstract
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Liver dysfunction and heart failure. Author(s): Cogger VC, Fraser R, Le Couteur DG. Source: The American Journal of Cardiology. 2003 June 1; 91(11): 1399. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767448&dopt=Abstract
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Living with heart failure: depression and quality of life in patients and spouses. Author(s): Martensson J, Dracup K, Canary C, Fridlund B. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 April; 22(4): 460-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681424&dopt=Abstract
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Location, size, and distribution of mediastinal lymph node enlargement in chronic congestive heart failure. Author(s): Erly WK, Borders RJ, Outwater EK, Zaetta JM, Borders GT. Source: Journal of Computer Assisted Tomography. 2003 July-August; 27(4): 485-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886129&dopt=Abstract
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Long-term effects of beta blocker therapy on P-wave duration and dispersion in congestive heart failure patients: a new effect? Author(s): Camsari A, Pekdemir H, Akkus MN, Yenihan S, Doven O, Cin VG. Source: Journal of Electrocardiology. 2003 April; 36(2): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764693&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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Long-term survival in patients hospitalized with congestive heart failure: relation to preserved and reduced left ventricular systolic function. Author(s): Gustafsson F, Torp-Pedersen C, Brendorp B, Seibaek M, Burchardt H, Kober L; DIAMOND Study Group. Source: European Heart Journal. 2003 May; 24(9): 863-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727154&dopt=Abstract
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Mechanisms of renal hyporesponsiveness to ANP in heart failure. Author(s): Charloux A, Piquard F, Doutreleau S, Brandenberger G, Geny B. Source: European Journal of Clinical Investigation. 2003 September; 33(9): 769-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925036&dopt=Abstract
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Metalloproteinases 2 and 9 are increased in plasma of patients with heart failure. Author(s): Altieri P, Brunelli C, Garibaldi S, Nicolino A, Ubaldi S, Spallarossa P, Olivotti L, Rossettin P, Barsotti A, Ghigliotti G. Source: European Journal of Clinical Investigation. 2003 August; 33(8): 648-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12864774&dopt=Abstract
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Metformin and thiazolidinedione use in Medicare patients with heart failure. Author(s): Masoudi FA, Wang Y, Inzucchi SE, Setaro JF, Havranek EP, Foody JM, Krumholz HM. Source: Jama : the Journal of the American Medical Association. 2003 July 2; 290(1): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837715&dopt=Abstract
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Metoprolol CR/XL in black patients with heart failure (from the Metoprolol CR/XL randomized intervention trial in chronic heart failure). Author(s): Goldstein S, Deedwania P, Gottlieb S, Wikstrand J; MERIT-HF Study Group. Source: The American Journal of Cardiology. 2003 August 15; 92(4): 478-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12914886&dopt=Abstract
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Metoprolol CR/XL in postmyocardial infarction patients with chronic heart failure: experiences from MERIT-HF. Author(s): Janosi A, Ghali JK, Herlitz J, Czuriga I, Klibaner M, Wikstrand J, Hjalmarson A; MERIT-HF Study Group. Source: American Heart Journal. 2003 October; 146(4): 721-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564329&dopt=Abstract
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Mortality in nursing home patients with congestive heart failure. Author(s): Aronow WS. Source: Journal of the American Medical Directors Association. 2003 July-August; 4(4): 220-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855917&dopt=Abstract
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Mortality trends for 23,505 Medicare patients hospitalized with heart failure in Northeast Ohio, 1991 to 1997. Author(s): Baker DW, Einstadter D, Thomas C, Cebul RD. Source: American Heart Journal. 2003 August; 146(2): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891193&dopt=Abstract
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Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Author(s): Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, Steiner JF, Ordin DL, Krumholz HM. Source: American Heart Journal. 2003 August; 146(2): 250-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891192&dopt=Abstract
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Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. Author(s): Cleland JG, Pennell DJ, Ray SG, Coats AJ, Macfarlane PW, Murray GD, Mule JD, Vered Z, Lahiri A; Carvedilol hibernating reversible ischaemia trial: marker of success investigators. Source: Lancet. 2003 July 5; 362(9377): 14-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853194&dopt=Abstract
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Myotrophin in human heart failure. Author(s): O'Brien RJ, Loke I, Davies JE, Squire IB, Ng LL. Source: Journal of the American College of Cardiology. 2003 August 20; 42(4): 719-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932609&dopt=Abstract
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Natriuretic peptides (NPs): Automated electrochemiluminescent immunoassay for Nterminal pro-BNP compared with IRMAs for ANP and BNP in heart failure patients and healthy individuals. Author(s): Prontera C, Emdin M, Zucchelli GC, Ripoli A, Passino C, Clerico A. Source: Clinical Chemistry. 2003 September; 49(9): 1552-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928247&dopt=Abstract
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Neither carvedilol nor bisoprolol in maximally tolerated doses has any specific advantage in lowering chronic heart failure oxidant stress: implications for betablocker selection. Author(s): Chin BS, Gibbs CR, Blann AD, Lip GY. Source: Clinical Science (London, England : 1979). 2003 October; 105(4): 507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841846&dopt=Abstract
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Neurohormonal determinants of peak oxygen uptake in patients with chronic heart failure. Author(s): Kinugawa T, Kato M, Ogino K, Igawa O, Hisatome I, Shigemasa C, Nohara R. Source: Japanese Heart Journal. 2003 September; 44(5): 725-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14587654&dopt=Abstract
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New developments in the management of heart failure: a review of the literature in 2002. Author(s): van der Sloot JA. Source: The Netherlands Journal of Medicine. 2003 May; 61(5 Suppl): 19-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918546&dopt=Abstract
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NICE issues new guidelines for patients with heart failure. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 2003 July 26; 327(7408): 179. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881236&dopt=Abstract
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Noncardiac comorbidity increases preventable hospitalizations and mortality among Medicare beneficiaries with chronic heart failure. Author(s): Braunstein JB, Anderson GF, Gerstenblith G, Weller W, Niefeld M, Herbert R, Wu AW. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1226-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522486&dopt=Abstract
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Nonpharmacologic care of heart failure: counseling, dietary restriction, rehabilitation, treatment of sleep apnea, and ultrafiltration. Author(s): Colonna P, Sorino M, D'Agostino C, Bovenzi F, De Luca L, Arrigo F, de Luca I. Source: The American Journal of Cardiology. 2003 May 8; 91(9A): 41F-50F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729849&dopt=Abstract
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Nonpharmacologic care of heart failure: patient, family, and hospital organization. Author(s): D'Alto M, Pacileo G, Calabro R. Source: The American Journal of Cardiology. 2003 May 8; 91(9A): 51F-54F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729850&dopt=Abstract
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Normalization for peak oxygen uptake increases the prognostic power of the ventilatory response to exercise in patients with chronic heart failure. Author(s): Guazzi M, De Vita S, Cardano P, Barlera S, Guazzi MD. Source: American Heart Journal. 2003 September; 146(3): 542-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947376&dopt=Abstract
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N-terminal pro B type natriuretic peptide, but not the new putative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure. Author(s): Fisher C, Berry C, Blue L, Morton JJ, McMurray J. Source: Heart (British Cardiac Society). 2003 August; 89(8): 879-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860863&dopt=Abstract
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On the rise: The current and projected future burden of congestive heart failure hospitalization in Canada. Author(s): Johansen H, Strauss B, Arnold JM, Moe G, Liu P. Source: The Canadian Journal of Cardiology. 2003 March 31; 19(4): 430-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704491&dopt=Abstract
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Opportunities for improvement in the diagnosis and treatment of heart failure. Author(s): McCullough PA, Philbin EF, Spertus JA, Sandberg KR, Sullivan RA, Kaatz S. Source: Clin Cardiol. 2003 May; 26(5): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769251&dopt=Abstract
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Optimal digoxin concentrations for patients with heart failure. Author(s): Carbonin P, Zuccala G. Source: Jama : the Journal of the American Medical Association. 2003 May 28; 289(20): 2643; Author Reply 2643-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771104&dopt=Abstract
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Optimal digoxin concentrations for patients with heart failure. Author(s): de Denus S, Spinler SA. Source: Jama : the Journal of the American Medical Association. 2003 May 28; 289(20): 2643; Author Reply 2643-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771103&dopt=Abstract
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Optimal management of outpatients with heart failure using advanced practice nurses in a hospital-based heart failure center. Author(s): Crowther M. Source: Journal of the American Academy of Nurse Practitioners. 2003 June; 15(6): 260-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861892&dopt=Abstract
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Orthopnea and inspiratory effort in chronic heart failure patients. Author(s): Nava S, Larovere MT, Fanfulla F, Navalesi P, Delmastro M, Mortara A. Source: Respiratory Medicine. 2003 June; 97(6): 647-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814149&dopt=Abstract
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Outcomes in heart failure patients with preserved ejection fraction: mortality, readmission, and functional decline. Author(s): Smith GL, Masoudi FA, Vaccarino V, Radford MJ, Krumholz HM. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1510-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742291&dopt=Abstract
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Out-of-hospital cardiac arrest--the relevance of heart failure. The Maastricht Circulatory Arrest Registry. Author(s): Gorgels AP, Gijsbers C, de Vreede-Swagemakers J, Lousberg A, Wellens HJ. Source: European Heart Journal. 2003 July; 24(13): 1204-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831814&dopt=Abstract
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Oxidative stress and heart failure. Author(s): Byrne JA, Grieve DJ, Cave AC, Shah AM. Source: Arch Mal Coeur Vaiss. 2003 March; 96(3): 214-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722552&dopt=Abstract
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Oxygen cost of exercise is increased in heart failure after accounting for recovery costs. Author(s): Mitchell SH, Steele NP, Leclerc KM, Sullivan M, Levy WC. Source: Chest. 2003 August; 124(2): 572-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907545&dopt=Abstract
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Pacing techniques in heart failure: current concepts and future outlook. Author(s): Abi-Samra FM. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 214-23, 229. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937358&dopt=Abstract
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Patients with both diabetes and heart failure often treated with medications government considers unsafe. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 August 8; 14(15): 1, 6-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964577&dopt=Abstract
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Polypharmacy and comorbidity in heart failure. Author(s): Masoudi FA, Krumholz HM. Source: Bmj (Clinical Research Ed.). 2003 September 6; 327(7414): 513-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958085&dopt=Abstract
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Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study. Author(s): Lewis EF, Moye LA, Rouleau JL, Sacks FM, Arnold JM, Warnica JW, Flaker GC, Braunwald E, Pfeffer MA; CARE Study. Source: Journal of the American College of Cardiology. 2003 October 15; 42(8): 1446-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563590&dopt=Abstract
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Predictors of nursing home admission for older adults hospitalized with heart failure. Author(s): Ahmed A, Allman RM, DeLong JF. Source: Archives of Gerontology and Geriatrics. 2003 March-April; 36(2): 117-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849086&dopt=Abstract
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Prevalence of self-reported heart failure among US adults: results from the 1999 National Health Interview Survey. Author(s): Ni H. Source: American Heart Journal. 2003 July; 146(1): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851619&dopt=Abstract
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Prevalence, predictors, and prognostic implications of improvement in left ventricular systolic function and clinical status in patients >70 years of age with recently diagnosed systolic heart failure. Author(s): Cioffi G, Stefenelli C, Tarantini L, Opasich C. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860218&dopt=Abstract
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Prognosis for South Asian and white patients newly admitted to hospital with heart failure in the United Kingdom: historical cohort study. Author(s): Blackledge HM, Newton J, Squire IB. Source: Bmj (Clinical Research Ed.). 2003 September 6; 327(7414): 526-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958110&dopt=Abstract
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Prognosis in heart failure with preserved left ventricular systolic function: prospective cohort study. Author(s): MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KA. Source: Bmj (Clinical Research Ed.). 2003 July 12; 327(7406): 78-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855525&dopt=Abstract
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Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classification. Author(s): Khot UN, Jia G, Moliterno DJ, Lincoff AM, Khot MB, Harrington RA, Topol EJ. Source: Jama : the Journal of the American Medical Association. 2003 October 22; 290(16): 2174-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570953&dopt=Abstract
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QRS duration variability in patients with heart failure. Author(s): Aranda JM, Carlson ER, Pauly DF, Curtis AB, Conti CR, Ariet M, Hill JA. Source: The American Journal of Cardiology. 2002 August 1; 90(3): 335-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127628&dopt=Abstract
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QRS duration: a simple marker for predicting cardiac mortality in ICD patients with heart failure. Author(s): Bode-Schnurbus L, Bocker D, Block M, Gradaus R, Heinecke A, Breithardt G, Borggrefe M. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1157-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975406&dopt=Abstract
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QRS interval time-related changes and prognosis in heart failure. Author(s): Grigioni F, Boriani G, Magelli C, Branzi A. Source: The American Journal of Cardiology. 2003 February 15; 91(4): 514. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586285&dopt=Abstract
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QT dispersion after beta-blocker therapy (carvedilol or metoprolol) in children with heart failure. Author(s): Etheridge SP, Shaddy RE. Source: The American Journal of Cardiology. 2003 June 15; 91(12): 1497-500, A8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804745&dopt=Abstract
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QT dispersion has no prognostic value in patients with symptomatic heart failure: an ELITE II substudy. Author(s): Gang Y, Ono T, Hnatkova K, Hashimoto K, Camm AJ, Pitt B, Poole-Wilson PA, Malik M; ELITE II investigators. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 394-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687853&dopt=Abstract
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QTc interval and B-type natriuretic peptide levels predict death in patients with advanced heart failure. Author(s): SoRelle R. Source: Circulation. 2003 April 8; 107(13): E9024-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682038&dopt=Abstract
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Qualitative analysis of living with heart failure. Author(s): Zambroski CH. Source: Heart & Lung : the Journal of Critical Care. 2003 January-February; 32(1): 32-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571546&dopt=Abstract
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Quality of care of nursing home residents hospitalized with heart failure. Author(s): Ahmed A, Weaver MT, Allman RM, DeLong JF, Aronow WS. Source: Journal of the American Geriatrics Society. 2002 November; 50(11): 1831-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410902&dopt=Abstract
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Quality of care of patients hospitalized with congestive heart failure. Author(s): Scott IA, Denaro CP, Flores JL, Bennett CJ, Hickey AC, Mudge AM, Atherton J; Brisbane Cardiac Consortium Leader Group. Source: Internal Medicine Journal. 2003 April; 33(4): 140-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680979&dopt=Abstract
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Quantification of proinflammatory cytokines in the urine of congestive heart failure patients. Its relationship with plasma levels. Author(s): Sirera R, Salvador A, Roldan I, Talens R, Gonzalez-Molina A, Rivera M. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 January; 5(1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559212&dopt=Abstract
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Racial disparities in care of heart failure. Author(s): FitzGerald D. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1316; Author Reply 1316-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966121&dopt=Abstract
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Randomized trial of a daily electronic home monitoring system in patients with advanced heart failure: the Weight Monitoring in Heart Failure (WHARF) trial. Author(s): Goldberg LR, Piette JD, Walsh MN, Frank TA, Jaski BE, Smith AL, Rodriguez R, Mancini DM, Hopton LA, Orav EJ, Loh E; WHARF Investigators. Source: American Heart Journal. 2003 October; 146(4): 705-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564327&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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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 impaired chronotropic response, cardiac output during exercise, and exercise tolerance in patients with chronic heart failure. Author(s): Samejima H, Omiya K, Uno M, Inoue K, Tamura M, Itoh K, Suzuki K, Akashi Y, Seki A, Suzuki N, Osada N, Tanabe K, Miyake F, Itoh H. Source: Japanese Heart Journal. 2003 July; 44(4): 515-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906033&dopt=Abstract
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Researchers probe anemia-heart failure link. Author(s): Mitka M. Source: Jama : the Journal of the American Medical Association. 2003 October 8; 290(14): 1835-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14532298&dopt=Abstract
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Resynchronization therapy for the treatment of heart failure. Author(s): Saxon LA, Ellenbogen KA. Source: Circulation. 2003 September 2; 108(9): 1044-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952826&dopt=Abstract
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Right heart failure and hyperthyroidism: a neglected presentation. Author(s): Cohen J, Schattner A. Source: The American Journal of Medicine. 2003 July; 115(1): 76-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867245&dopt=Abstract
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Robotic-enhanced biventricular resynchronization: an alternative to endovenous cardiac resynchronization therapy in chronic heart failure. Author(s): Jansens JL, Jottrand M, Preumont N, Stoupel E, de Canniere D. Source: The Annals of Thoracic Surgery. 2003 August; 76(2): 413-7; Discussion 417. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902075&dopt=Abstract
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Role of the plasma brain natriuretic peptide in differentiating patients with congestive heart failure from other diseases. Author(s): Sirithunyanont C, Leowattana W, Sukumalchantra Y, Chaisupamonkollarp S, Watanawaroon S, Chivatanaporn B, Bhuripanyo K, Mahanonda N. Source: J Med Assoc Thai. 2003 May; 86 Suppl 1: S87-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866774&dopt=Abstract
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Sarcoplasmic reticulum Ca2+ and heart failure: roles of diastolic leak and Ca2+ transport. Author(s): Bers DM, Eisner DA, Valdivia HH. Source: Circulation Research. 2003 September 19; 93(6): 487-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500331&dopt=Abstract
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Screening for left ventricular systolic dysfunction among patients with risk factors for heart failure. Author(s): Baker DW, Bahler RC, Finkelhor RS, Lauer MS. Source: American Heart Journal. 2003 October; 146(4): 736-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564331&dopt=Abstract
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Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Author(s): Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C, Di Meglio F, Nadal-Ginard B, Frustaci A, Leri A, Maseri A, Anversa P. Source: Circulation Research. 2003 October 3; 93(7): 604-13. Epub 2003 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958145&dopt=Abstract
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Serum insulin-like growth factor I and risk for heart failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study. Author(s): Vasan RS, Sullivan LM, D'Agostino RB, Roubenoff R, Harris T, Sawyer DB, Levy D, Wilson PW. Source: Annals of Internal Medicine. 2003 October 21; 139(8): 642-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14568852&dopt=Abstract
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Should aspirin be used with angiotensin-converting enzyme inhibitors in patients with chronic heart failure? Author(s): Park MH. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 July-August; 9(4): 206-11; Quiz 212-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12937357&dopt=Abstract
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Sleep-disordered breathing in heart failure: characteristics and implications. Author(s): Lanfranchi PA, Somers VK. Source: Respiratory Physiology & Neurobiology. 2003 July 16; 136(2-3): 153-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853007&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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Statin helps heart failure patients without high cholesterol. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2003 August 22; 14(16): 1, 5-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966938&dopt=Abstract
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Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial. Author(s): Cohn JN, Anand IS, Latini R, Masson S, Chiang YT, Glazer R; Valsartan Heart Failure Trial Investigators. Source: Circulation. 2003 September 16; 108(11): 1306-9. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939207&dopt=Abstract
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Symposium reporter 2003. New therapeutic options in the management of hypertension to heart failure. Orlando, Florida, USA, March 6, 2003. Author(s): Cohn JN, Velazquez EJ, Musher J. Source: Journal of the American Medical Directors Association. 2003; : 1-16, Quiz 17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924409&dopt=Abstract
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The costs and outcomes of multifaceted interventions designed to improve the care of congestive heart failure in the inpatient setting: a review of the literature. Author(s): Balinsky W, Muennig P. Source: Medical Care Research and Review : Mcrr. 2003 September; 60(3): 275-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971230&dopt=Abstract
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The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis. Author(s): Heeneman S, Cleutjens JP, Faber BC, Creemers EE, van Suylen RJ, Lutgens E, Cleutjens KB, Daemen MJ. Source: The Journal of Pathology. 2003 July; 200(4): 516-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845619&dopt=Abstract
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The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. Author(s): Domanski M, Krause-Steinrauf H, Deedwania P, Follmann D, Ghali JK, Gilbert E, Haffner S, Katz R, Lindenfeld J, Lowes BD, Martin W, McGrew F, Bristow MR; BEST Investigators. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 914-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957443&dopt=Abstract
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The effects of alpha and beta blockade on ventilatory responses to exercise in chronic heart failure. Author(s): Witte KK, Thackray SD, Nikitin NP, Cleland JG, Clark AL. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975409&dopt=Abstract
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The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial. Author(s): Roveda F, Middlekauff HR, Rondon MU, Reis SF, Souza M, Nastari L, Barretto AC, Krieger EM, Negrao CE. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 854-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957432&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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Thermal hydrotherapy improves quality of life and hemodynamic function in patients with chronic heart failure. Author(s): Michalsen A, Ludtke R, Buhring M, Spahn G, Langhorst J, Dobos GJ. Source: American Heart Journal. 2003 October; 146(4): E11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564334&dopt=Abstract
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Thiazolidinedione-associated congestive heart failure and pulmonary edema. Author(s): Kermani A, Garg A. Source: Mayo Clinic Proceedings. 2003 September; 78(9): 1088-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962163&dopt=Abstract
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Thromboxane inhibition improves renal perfusion and excretory function in severe congestive heart failure. Author(s): Castellani S, Paniccia R, Di Serio C, La Cava G, Poggesi L, Fumagalli S, Gensini GF, Neri Serneri GG. Source: Journal of the American College of Cardiology. 2003 July 2; 42(1): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849673&dopt=Abstract
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Trends and ethnic differences in hospital admissions and mortality for congestive heart failure in the elderly in Singapore, 1991 to 1998. Author(s): Ng TP, Niti M. Source: Heart (British Cardiac Society). 2003 August; 89(8): 865-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860859&dopt=Abstract
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Update on therapy for heart failure. Author(s): DiBianco R. Source: The American Journal of Medicine. 2003 October 15; 115(6): 480-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563505&dopt=Abstract
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Use of aspirin in conjunction with angiotensin-converting enzyme inhibitors does not worsen long-term survival in heart failure. Author(s): Harjai KJ, Solis S, Prasad A, Loupe J. Source: International Journal of Cardiology. 2003 April; 88(2-3): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714200&dopt=Abstract
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Use of beta-blockers in congestive heart failure. Author(s): Sallach JA, Goldstein S. Source: Annals of Medicine. 2003; 35(4): 259-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846268&dopt=Abstract
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Use of carvedilol in the treatment of heart failure. Author(s): Coats A. Source: Hosp Med. 2003 May; 64(5): 288-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789738&dopt=Abstract
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Use of spironolactone in heart failure patients receiving angiotensin-converting enzyme inhibitors and beta-blockers. Author(s): Ahmed A. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1851-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767683&dopt=Abstract
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Use of the Jarvik 2000 left ventricular assist system as a bridge to heart transplantation or as destination therapy for patients with chronic heart failure. Author(s): Frazier OH, Myers TJ, Westaby S, Gregoric ID. Source: Annals of Surgery. 2003 May; 237(5): 631-6; Discussion 636-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724629&dopt=Abstract
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Usefulness of anemia as a predictor of death and rehospitalization in patients with decompensated heart failure. Author(s): Felker GM, Gattis WA, Leimberger JD, Adams KF, Cuffe MS, Gheorghiade M, O'Connor CM. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 625-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943893&dopt=Abstract
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Usefulness of combined Doppler indexes in predicting left ventricular filling pressures in patients with acute heart failure. Author(s): Arques S. Source: The American Journal of Cardiology. 2003 September 1; 92(5): 649-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943902&dopt=Abstract
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Using a gene-switch transgenic approach to dissect distinct roles of MAP kinases in heart failure. Author(s): Petrich BG, Liao P, Wang Y. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 429-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858568&dopt=Abstract
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Utility of N-terminal pro-brain natriuretic peptide for the diagnosis of heart failure. Author(s): Lose JV, Gupta SN, Selvakumar D. Source: Indian Heart J. 2003 January-February; 55(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760585&dopt=Abstract
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Variable patterns of septal activation in patients with left bundle branch block and heart failure. Author(s): Rodriguez LM, Timmermans C, Nabar A, Beatty G, Wellens HJ. Source: Journal of Cardiovascular Electrophysiology. 2003 February; 14(2): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693492&dopt=Abstract
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Vascular endothelium in tissue remodeling: implications for heart failure. Author(s): Dallabrida SM, Rupnick MA. Source: Cold Spring Harb Symp Quant Biol. 2002; 67: 417-27. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858567&dopt=Abstract
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Vasopeptidase inhibitors in heart failure. Author(s): Dawson A, Struthers AD. Source: J Renin Angiotensin Aldosterone Syst. 2002 September; 3(3): 156-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563565&dopt=Abstract
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Vasopeptidase inhibitors: potential role in the treatment of heart failure. Author(s): Trindade PT, Rouleau JL. Source: Heart Fail Monit. 2001; 2(1): 2-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634892&dopt=Abstract
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Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Author(s): Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C; Tolvaptan Investigators. Source: Circulation. 2003 June 3; 107(21): 2690-6. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742979&dopt=Abstract
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Vasopressin: a new target for the treatment of heart failure. Author(s): Lee CR, Watkins ML, Patterson JH, Gattis W, O'connor CM, Gheorghiade M, Adams KF Jr. Source: American Heart Journal. 2003 July; 146(1): 9-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851603&dopt=Abstract
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Ventricular aneurysms, shock, and late follow-up in patients with heart failure. Author(s): McCarthy PM. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 August; 126(2): 323-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928624&dopt=Abstract
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Ventricular non-compaction: a rare cause of heart failure. Author(s): Wong SP, Oldfield M, Ko AP, Kerr AJ. Source: Internal Medicine Journal. 2003 May-June; 33(5-6): 262-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752900&dopt=Abstract
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Ventricular remodeling does not accompany the development of heart failure in diabetic patients after myocardial infarction. Author(s): Marfella R, Verza M, Giugliano D. Source: Circulation. 2003 April 8; 107(13): E85; Author Reply E85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682032&dopt=Abstract
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Verbal memory impairment in congestive heart failure. Author(s): Antonelli Incalzi R, Trojano L, Acanfora D, Crisci C, Tarantino F, Abete P, Rengo F; CHF Italian Study Investigators. Source: J Clin Exp Neuropsychol. 2003 February; 25(1): 14-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607168&dopt=Abstract
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What do patients know about their heart failure? Author(s): Artinian NT, Magnan M, Christian W, Lange MP. Source: Applied Nursing Research : Anr. 2002 November; 15(4): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444578&dopt=Abstract
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What factors influence provider knowledge of a congestive heart failure guideline in a national health care system? Author(s): Welke KF, BootsMiller BJ, McCoy KD, Vaughn TE, Ward MM, Flach SD, Peloso PM, Sorofman BA, Tripp-Reimer T, Doebbeling BN. Source: American Journal of Medical Quality : the Official Journal of the American College of Medical Quality. 2003 May-June; 18(3): 122-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836902&dopt=Abstract
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What happened to evidence in NICE guidance on heart failure? Author(s): Robson J. Source: Bmj (Clinical Research Ed.). 2003 October 18; 327(7420): 932. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563774&dopt=Abstract
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What is the meaning of LIFE? Implications of the Losartan Intervention for Endpoint reduction in hypertension trial for heart failure physicians. Author(s): Massie BM. Source: Journal of Cardiac Failure. 2002 August; 8(4): 197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397565&dopt=Abstract
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What is the most effective beta-blocker for heart failure? Author(s): Neher JO, Safranek S, Grover F Jr. Source: The Journal of Family Practice. 2003 May; 52(5): 396, 398-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737773&dopt=Abstract
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What makes the new heart failure guidelines tick? Serving as an adjunct to the NYHA's classification, the ACC/AHA system assesses objective signs of heart disease. Author(s): Bosen DM; American College of Cardiology; American Heart Association. Source: Nursing Management. 2003 February; 34(2): 44A-B. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576783&dopt=Abstract
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When lymphoma and heart failure cross paths. Author(s): Nomiyama K, Shibuya T, Kataoka C, Aoki Y. Source: Journal of Hematotherapy & Stem Cell Research. 2003 February; 12(1): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662430&dopt=Abstract
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Which patients with congestive heart failure may benefit from biventricular pacing? Author(s): Galizio NO, Pesce R, Valero E, Gonzalez JL, Favaloro RR, Favaloro L, Perrone S, Davila P, Godoy M. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 158-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687804&dopt=Abstract
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Will endothelin receptor antagonists have a role in heart failure? Author(s): Spieker LE, Luscher TF. Source: The Medical Clinics of North America. 2003 March; 87(2): 459-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693734&dopt=Abstract
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Worsening renal function: what is a clinically meaningful change in creatinine during hospitalization with heart failure? Author(s): Smith GL, Vaccarino V, Kosiborod M, Lichtman JH, Cheng S, Watnick SG, Krumholz HM. Source: Journal of Cardiac Failure. 2003 February; 9(1): 13-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612868&dopt=Abstract
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CHAPTER 2. NUTRITION AND HEART FAILURE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and heart failure.
Finding Nutrition Studies on Heart Failure 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.4 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 “heart failure” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
4
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 “heart failure” (or a synonym): •
“BNP” for heart failure: role of nesiritide in cardiovascular therapeutics. Author(s): Kaufman Center for Heart Failure, Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. Source: Mills, R M Hobbs, R E Young, J B Congest-Heart-Fail. 2002 Sep-October; 8(5): 270-3 1527-5299
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A new look at heart failure. Author(s): Kent State University, 400 East Fourth Street, East Liverpool, Ohio 43920, USA.
[email protected] Source: Thomas, D J Harrah, B F Home-Healthc-Nurse. 2000 March; 18(3): 164-70; quiz 171 0884-741X
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Aggressive therapy of congestive heart failure and associated chronic renal failure with medications and correction of anemia stops or slows the progression of both diseases. Author(s): Department of Nephrology, Tel Aviv Medical Center, Israel.
[email protected] Source: Silverberg, D S Wexler, D Blum, M Sheps, D Schwartz, D Yachnin, T Baruch, R Tchebiner, J Zubkov, A Shaked, M Steinbruch, S Keren, G Iaina, A Perit-Dial-Int. 2001; 21 Suppl 3: S236-40 0896-8608
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Angiotensin II receptor antagonists for the treatment of heart failure: what is their place after ELITE-II and Val-HeFT? Author(s): CRI in Heart Failure, University of Glasgow, Glasgow, G12 8QQ, UK.
[email protected] Source: McMurray, J J J-Renin-Angiotensin-Aldosterone-Syst. 2001 June; 2(2): 89-92 1470-3203
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Anticoagulation for heart failure in sinus rhythm: a Cochrane systematic review. Author(s): Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
[email protected] Source: Lip, G Y Gibbs, C R QJM. 2002 July; 95(7): 451-9 1460-2725
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Antiplatelet agents versus control or anticoagulation for heart failure in sinus rhythm: a Cochrane systematic review. Author(s): Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
[email protected] Source: Lip, G Y Gibbs, C R QJM. 2002 July; 95(7): 461-8 1460-2725
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Balancing diuretic therapy in heart failure: loop diuretics, thiazides, and aldosterone antagonists. Author(s): Heart Failure Clinic, Medical University of South Carolina, Charleston, SC, USA.
[email protected] Source: Paul, S Congest-Heart-Fail. 2002 Nov-December; 8(6): 307-12 1527-5299
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Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure. Author(s): Department of Medicine III, University of Cologne, Cologne, Germany.
[email protected] Source: Lindner, M Brandt, M C Sauer, H Hescheler, J Bohle, T Beuckelmann, D J CellCalcium. 2002 April; 31(4): 175-82 0143-4160
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Carvedilol in the treatment of chronic heart failure. Author(s): Terrence Donnelly Heart Center, St Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, M5B1W8, Canada.
[email protected] Source: Moe, G Expert-Opin-Pharmacother. 2001 May; 2(5): 831-43 1465-6566
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Central AT1 receptors are involved in the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure. Author(s): Department of Physiology and Biophysics, University of Nebraska College of Medicine, 984575 Nebraska Medical Center, Omaha, NE 68198-4575, USA. Source: Zhu, G Q Zucker, I H Wang, W Basic-Res-Cardiol. 2002 July; 97(4): 320-6 03008428
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Characteristics and treatment of patients with heart failure in the emergency department. Author(s): College of Nursing, University of Kentucky, Lexington, USA.
[email protected] Source: Welsh, J Darlene Heiser, Regina M Schooler, Mary P Brockopp, Dorothy Y Parshall, Mark B Cassidy, Karma B Saleh, Usama J-Emerg-Nurs. 2002 April; 28(2): 12631 0099-1767
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Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA class II. Source: Zapfe June, G. Phytomedicine. Stuttgart; New York : G. Fischer, c1994-. July 2001. volume 8 (4) page 262-266. 0944-7113
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Clinical trials update: The Heart Protection Study, IONA, CARISA, ENRICHD, ACUTE, ALIVE, MADIT II and REMATCH. Impact Of Nicorandil on Angina. Combination Assessment of Ranolazine In Stable Angina. ENhancing Recovery In Coronary Heart Disease patients. Assessment of Cardioversion Using Transoesophageal Echocardiography. AzimiLide post-Infarct surVival Evaluation. Randomised Evaluation of Mechanical Assistance for Treatment of Chronic Heart failure. Author(s): Department of Academic Cardiology, Castle Hill Hospital, Cottingham, HU16 5JQ, Kingston upon Hull, UK. Source: Louis, Amala A Manousos, I Renata Coletta, Alison P Clark, Andrew L Cleland, John G F Eur-J-Heart-Fail. 2002 January; 4(1): 111-6 1388-9842
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Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension. Author(s): Department of Pharmacology, Osaka City University Medical School, Japan. Source: Namba, M Kim, S Zhan, Y Nakao, T Iwao, H Hypertens-Res. 2002 May; 25(3): 461-6 0916-9636
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Conditioned nutritional requirements: therapeutic relevance to heart failure. Author(s): University of Toronto, Toronto, Canada.
[email protected] Source: Sole, Michael J Jeejeebhoy, Kursheed N Herz. 2002 March; 27(2): 174-8 0340-9937
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Congestive heart failure performance-improvement project: special needs for special patients. Author(s):
[email protected] Source: Bryant, P K Lippincotts-Case-Manag. 2002 Jul-August; 7(4): 152-62 1529-7764
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Current guidelines in heart failure management. Author(s): Department of Medicine, University of Texas, MD Anderson Cancer Center, Houston, USA.
[email protected] Source: Durand, Jean Bernard Ethn-Dis. 2002 Winter; 12(1): S1-3-11 1049-510X
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Dissociation between hemodynamic changes and symptom improvement in patients with advanced congestive heart failure. Author(s): Duke Clinical Research Institute, P.O. Box 17969,Durham, NC 27715, USA.
[email protected] Source: Shah, M R Hasselblad, V Stinnett, S S Kramer, J M Grossman, S Gheorghiade, M Adams, K F Jr Swedberg, K Califf, R M O'Connor, C M Eur-J-Heart-Fail. 2002 June; 4(3): 297-304 1388-9842
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Effect of phosphodiesterase III inhibitor on plasma concentrations of endothelin-1 and tumour necrosis factor in patients with acute heart failure. Author(s): Department of Medicine, Misato Junshin Hospital, Saitama, Japan. Source: Nakamura, T Suzuki, S Ushiyama, C Shimada, N Koide, H Acta-Cardiol. 2002 February; 57(1): 19-21 0001-5385
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Effect of thalidomide on the skeletal muscle in experimental heart failure. Author(s): Internal Medicine, Adria Hospital, Italy.
[email protected] Source: Vescovo, G Ravara, B Angelini, A Sandri, M Carraro, U Ceconi, C Dalla Libera, L Eur-J-Heart-Fail. 2002 August; 4(4): 455-60 1388-9842
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Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure. Author(s): Second Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Source: Takahashi, K Osanai, T Nakano, T Wakui, M Okumura, K Heart-Vessels. 2002 September; 16(6): 249-56 0910-8327
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Facilitators and barriers to heart failure self-care. Author(s): Sharp HealthCare and School of Nursing, San Diego State University, San Diego, CA 92182-4158, USA.
[email protected] Source: Riegel, B Carlson, B Patient-Educ-Couns. 2002 April; 46(4): 287-95 0738-3991
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Free radicals in heart failure: therapeutic targets for old and new drugs. Author(s): Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, GA 30322, USA.
[email protected] Source: Zafari, A Maziar Harrison, David G Congest-Heart-Fail. 2002 May-June; 8(3): 129-30 1527-5299
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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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Hypertrophic osteoarthropathy caused by PGE1 in a patient with congestive heart failure during cardiac rehabilitation. Author(s): Department of Physical Medicine and Rehabilitation, General Hospital Vienna, University of Vienna, Austria.
[email protected] Source: Crevenna, R Quittan, M Hulsmann, M Wiesinger, G F Keilani, M Y Kainberger, F Leitha, T Fialka Moser, V Pacher, R Wien-Klin-Wochenschr. 2002 February 15; 114(3): 115-8 0043-5325
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Hypomagnesemia and concurrent acid-base and electrolyte abnormalities in patients with congestive heart failure. Author(s): Department of Internal Medicine, Medical School University of Ioannina, GR 45110, Ioannina, Greece.
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Source: Milionis, Haralampos J Alexandrides, George E Liberopoulos, Evangelos N Bairaktari, Eleni T Goudevenos, John Elisaf, Moses S Eur-J-Heart-Fail. 2002 March; 4(2): 167-73 1388-9842 •
Improving the quality of home care for patients with heart failure. Author(s): Covenant Home Health & Hospice, Milwaukee, Wisconsin, USA.
[email protected] Source: Gorski, Lisa A Caring. 2002 March; 21(3): 10-4 0738-467X
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Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. Author(s): UCLA Department of Medicine, Los Angeles, California, USA. Source: Horwich, T B Hamilton, M A Maclellan, W R Fonarow, G C J-Card-Fail. 2002 August; 8(4): 216-24 1071-9164
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Malnutrition in patients suffering from chronic heart failure; the nurse's care. Author(s): Department of Medicine, Cardiac Care Unit, Halmstad Central Hospital, 301 85 Halmstad, Sweden. Source: Jacobsson, A Pihl Lindgren, E Fridlund, B Eur-J-Heart-Fail. 2001 August; 3(4): 449-56 1388-9842
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Management of heart failure in the elderly. Author(s): Associate Professor of Medicine, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
[email protected] Source: Rich, Michael W Heart-Fail-Revolume 2002 January; 7(1): 89-97 1382-4147
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Managing heart failure with immunomodulatory agents. Author(s): DeBakey Heart Center, Methodist Hospital, Winters Center for Heart Failure Research, Gene and Judy Campbell Laboratory for Transplant Research, Department of Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas, USA. Source: Lisman, K A Stetson, S J Koerner, M M Farmer, J A Torre Amione, G CardiolClin. 2001 November; 19(4): 617-25 0733-8651
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Myocardial bradykinin following acute angiotensin-converting enzyme inhibition, AT1 receptor blockade, or combined inhibition in congestive heart failure. Author(s): Medical University of South Carolina, Charleston, SC 29425, USA. Source: Multani, M M Krombach, R S Goldberg, A T King, M K Hendrick, J W Sample, J A Baicu, S C Joffs, C deGasparo, M Spinale, F G J-Cardiovasc-Pharmacol-Ther. 2001 October; 6(4): 369-76 1074-2484
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Natriuretic peptides and salt sensitivity: endocrine cardiorenal integration in heart failure. Author(s): SUNY Upstate Medical University and Veterans Affairs Hospital, Syracuse, NY 13210, USA.
[email protected] Source: Villarreal, Daniel Freeman, Ronald H Reams, Garry P Congest-Heart-Fail. 2002 Jan-February; 8(1): 29-36, 48 1527-5299
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Nesiritide therapy for decompensated heart failure. Author(s): Department of Cardiology, Cardia Surgery, Sinai Hospital of Baltimore, MD 21215, USA.
[email protected] Source: Rempher, Kenneth J Clin-Nurse-Spec. 2002 May; 16(3): 157-9 0887-6274
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New therapeutic choices in the management of acute congestive heart failure. Author(s): Kaufman Center for Heart Failure, Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA. Source: Young, J B Rev-Cardiovasc-Med. 2001; 2 Suppl 2: S19-24 1530-6550
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Pharmacoeconomic considerations in assessing and selecting congestive heart failure therapies. Author(s): Laboratory of Health Organization Economics and Management, Paris Dauphine University, Paris, France.
[email protected] Source: Levy, E Levy, P Pharmacoeconomics. 2002; 20(14): 963-77 1170-7690
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Positive inotropic drug infusions for patients with heart failure: current controversies and best practice. Author(s): Covenant Home Health & Hospice, Milwaukee, WI, USA.
[email protected] Source: Gorski, Lisa A Home-Healthc-Nurse. 2002 April; 20(4): 244-53; quiz 253-4 0884741X
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Present and future pharmacotherapy for heart failure. Author(s): Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, QLD 4072, Australia.
[email protected] Source: Doggrell, S A Brown, L Expert-Opin-Pharmacother. 2002 July; 3(7): 915-30 14656566
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Prevention of cardiovascular failure, and stroke. Author(s): Geriatric Medicine Cleveland Clinic Foundation,
[email protected] Source: Messinger Rapport, B J 83, vii 0749-0690
diseases. Coronary artery disease, congestive heart Section, Department of General Internal Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Sprecher, D Clin-Geriatr-Med. 2002 August; 18(3): 463-
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Proinflammatory cytokine inhibitor prolongs the survival of rats with heart failure induced by pressure overload. Author(s): Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan. Source: Shioi, T Matsumori, A Kakio, T Kihara, Y Sasayama, S Jpn-Circ-J. 2001 June; 65(6): 584-5 0047-1828
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Quality assessment and quality control of echocardiographic performance in a large multicenter international study: Valsartan in heart failure trial (Val-HeFT). Author(s): VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd. 500/6641, Los Angeles, CA 90073, USA.
[email protected] Source: Wong, Maylene Staszewsky, Lidia Volpi, Alberto Latini, Roberto Barlera, Simona Hoglund, Christer J-Am-Soc-Echocardiogr. 2002 April; 15(4): 293-301 0894-7317
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Recent heart failure trials of neurohormonal modulation (OVERTURE and ENABLE): approaching the asymptote of efficacy? Author(s): School of Medicine, University of California, and the Section of Cardiology, Veterans Affairs Medical Center, San Francisco, CA 94121-1545, USA. Source: Teerlink, J R J-Card-Fail. 2002 June; 8(3): 124-7 1071-9164
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Role of nitric oxide in regulation of coronary blood flow in response to increased metabolic demand in dogs with pacing-induced heart failure. Author(s): Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan Source: Tada, H Egashira, K Yamamoto, M Usui, M Arai, Y Katsuda, Y Shimokawa, H Takeshita, A Jpn-Circ-J. 2001 September; 65(9): 827-33 0047-1828
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Selective endothelin receptor blockade reverses mitochondrial dysfunction in canine heart failure. Author(s): The Molecular Cardiology and Neuromuscular Institute, Highland Park, New Jersey 08904, USA. Source: Marin Garcia, J Goldenthal, M J Moe, G W J-Card-Fail. 2002 October; 8(5): 326-32 1071-9164
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Self-care behaviour of patients with heart failure. Author(s): Department of Nursing Science, University of Maastricht, Maastricht, The Netherlands. Source: Jaarsma, T Abu Saad, H H Dracup, K Halfens, R Scand-J-Caring-Sci. 2000; 14(2): 112-9 0283-9318
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The use of partial fatty acid oxidation inhibitors for metabolic therapy of angina pectoris and heart failure. Author(s): Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology, University of Marburg, Germany.
[email protected] Source: Rupp, H Zarain Herzberg, A Maisch, B Herz. 2002 November; 27(7): 621-36 0340-9937
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Thyroid hormone metabolism in patients with congestive heart failure: the low triiodothyronine state. Author(s): Division of Circulatory Physiology, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
[email protected] Source: Ascheim, D D Hryniewicz, K Thyroid. 2002 June; 12(6): 511-5 1050-7256
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Vasopeptidase inhibitors in heart failure. Author(s): Department of Clinical Pharmacology Therapeutics, University of Dundee, Ninewells Hospital, Dundee, Scotland. Source: Dawson, A Struthers, A D J-Renin-Angiotensin-Aldosterone-Syst. 2002 September; 3(3): 156-9 1470-3203
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
The following is a specific Web list relating to heart failure; 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 Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Thiamine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B1 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B1 (Thiamine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Angiotensin-Converting Enzyme (ACE) Inhibitors Source: Healthnotes, Inc.; www.healthnotes.com Calcium-Channel Blockers Source: Healthnotes, Inc.; www.healthnotes.com Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Carnitine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10012,00.html Carnitine (L-carnitine) Source: Integrative Medicine Communications; www.drkoop.com Creatine Source: Prima Communications, Inc.www.personalhealthzone.com Creatine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10020,00.html Creatine Monohydrate Source: Healthnotes, Inc.; www.healthnotes.com HMG-COA Reductase Inhibitors (Statins) Source: Integrative Medicine Communications; www.drkoop.com L-carnitine Source: Healthnotes, Inc.; www.healthnotes.com L-carnitine Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Potassium Source: Healthnotes, Inc.; www.healthnotes.com
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Spironolactone Source: Healthnotes, Inc.; www.healthnotes.com •
Food and Diet Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Juices Source: Healthnotes, Inc.; www.healthnotes.com Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND HEART FAILURE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to heart failure. 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 heart failure 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 “heart failure” (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 heart failure: •
A comparative observation on treatment of heart failure due to diastolic insufficiency of the left ventricle--a report of 43 cases. Author(s): Zhou S, Yang W, Bo X, Li Y, Hu X, Wu D. Source: J Tradit Chin Med. 1998 September; 18(3): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453605&dopt=Abstract
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A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure. Author(s): Keith ME, Jeejeebhoy KN, Langer A, Kurian R, Barr A, O'Kelly B, Sole MJ. Source: The American Journal of Clinical Nutrition. 2001 February; 73(2): 219-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157316&dopt=Abstract
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A new approach to assist postoperative heart failure in an animal model: juxta-aortic counterpulsation. Author(s): Fischer EI, Christen AI, Risk MR, Pessana FM, de Forteza E. Source: Artificial Organs. 2002 October; 26(10): 819-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296919&dopt=Abstract
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A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II. Author(s): Degenring FH, Suter A, Weber M, Saller R. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10(5): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833999&dopt=Abstract
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Acupuncture inhibits sympathetic activation during mental stress in advanced heart failure patients. Author(s): Middlekauff HR, Hui K, Yu JL, Hamilton MA, Fonarow GC, Moriguchi J, Maclellan WR, Hage A. Source: Journal of Cardiac Failure. 2002 December; 8(6): 399-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528093&dopt=Abstract
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Adult stem cell therapy for heart failure. Author(s): Chiu RC. Source: Expert Opinion on Biological Therapy. 2003 April; 3(2): 215-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662137&dopt=Abstract
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Altered baroreflex gain during voluntary breathing in chronic heart failure. Author(s): Mangin L, Monti A, Medigue C, Macquin-Mavier I, Lopes M, Gueret P, Castaigne A, Swynghedauw B, Mansier P. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2001 March; 3(2): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246056&dopt=Abstract
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Alternative therapies: Part II. Congestive heart failure and hypercholesterolemia. Author(s): Morelli V, Zoorob RJ. Source: American Family Physician. 2000 September 15; 62(6): 1325-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11011861&dopt=Abstract
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An exploratory study of developmental growth in adults with heart failure. Author(s): Baas LS, Beery TA, Fontana JA, Wagoner LE.
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Source: Journal of Holistic Nursing : Official Journal of the American Holistic Nurses' Association. 1999 June; 17(2): 117-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633647&dopt=Abstract •
Analysis of a large cohort of health maintenance organization patients with congestive heart failure. Author(s): Gladowski P, Fetterolf D, Beals S, Holleran MK, Reich S. Source: American Journal of Medical Quality : the Official Journal of the American College of Medical Quality. 2003 March-April; 18(2): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710556&dopt=Abstract
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Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized, placebo-controlled study in patients with congestive heart failure. Author(s): de Milliano PA, de Groot AC, Tijssen JG, van Eck-Smit BL, Van Zwieten PA, Lie KI. Source: American Heart Journal. 2002 August; 144(2): E3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177661&dopt=Abstract
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Cardiac natriuretic peptides: new laboratory parameters in heart failure patients. Author(s): Hammerer-Lercher A, Puschendorf B, Mair J. Source: Clin Lab. 2001; 47(5-6): 265-77. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405605&dopt=Abstract
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Cell therapy of heart failure. Author(s): Menasche P. Source: Comptes Rendus Biologies. 2002 June; 325(6): 731-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360861&dopt=Abstract
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Cerebral blood flow in patients with chronic heart failure before and after heart transplantation. Author(s): Gruhn N, Larsen FS, Boesgaard S, Knudsen GM, Mortensen SA, Thomsen G, Aldershvile J. Source: Stroke; a Journal of Cerebral Circulation. 2001 November; 32(11): 2530-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692012&dopt=Abstract
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Chronic vasopressin V(1A) but not V(2) receptor antagonism prevents heart failure in chronically infarcted rats. Author(s): Van Kerckhoven R, Lankhuizen I, van Veghel R, Saxena PR, Schoemaker RG. Source: European Journal of Pharmacology. 2002 August 2; 449(1-2): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163117&dopt=Abstract
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Clinical efficacy of crataegus extract WS 1442 in congestive heart failure NYHA class II. Author(s): Zapfe jun G. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 July; 8(4): 262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515715&dopt=Abstract
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Clinical observation on treatment of obstinate heart failure by supplementing qi and activating blood flow. Author(s): Shao J. Source: J Tradit Chin Med. 1997 September; 17(3): 187-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437192&dopt=Abstract
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Clinical study on chronopharmacokinetics of digoxin in patients with congestive heart failure. Author(s): Liu Z, Fang S, Wang L, Zhu T, Yang H, Yu S. Source: J Tongji Med Univ. 1998; 18(1): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10806796&dopt=Abstract
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Comorbidity in heart failure in the elderly. Author(s): McGann PE. Source: Clinics in Geriatric Medicine. 2000 August; 16(3): 631-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918651&dopt=Abstract
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Conditioned nutritional requirements: therapeutic relevance to heart failure. Author(s): Sole MJ, Jeejeebhoy KN. Source: Herz. 2002 March; 27(2): 174-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025462&dopt=Abstract
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Congestive heart failure caused by digitalis toxicity in an elderly man taking a licorice-containing chinese herbal laxative. Author(s): Harada T, Ohtaki E, Misu K, Sumiyoshi T, Hosoda S. Source: Cardiology. 2002; 98(4): 218. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566654&dopt=Abstract
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Congestive heart failure induces downregulation of P2X1-receptors in resistance arteries. Author(s): Malmsjo M, Bergdahl A, Moller S, Zhao XH, Sun XY, Hedner T, Edvinsson L, Erlinge D. Source: Cardiovascular Research. 1999 July; 43(1): 219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10536707&dopt=Abstract
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Congestive heart failure performance-improvement project: special needs for special patients. Author(s): Bryant PK. Source: Lippincott's Case Management : Managing the Process of Patient Care. 2002 July-August; 7(4): 152-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151809&dopt=Abstract
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Coronary artery bypass surgery in heart failure patients with chronic reversible and irreversible myocardial dysfunction: effect on heart rate variability. Author(s): Wiggers H, Botker HE, Egeblad H, Christiansen EH, Nielsen TT, Molgaard H. Source: Cardiology. 2002; 98(4): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566646&dopt=Abstract
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Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival. Author(s): Pagano D, Lewis ME, Townend JN, Davies P, Camici PG, Bonser RS. Source: Heart (British Cardiac Society). 1999 December; 82(6): 684-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10573493&dopt=Abstract
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Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. Author(s): Hambrecht R, Hilbrich L, Erbs S, Gielen S, Fiehn E, Schoene N, Schuler G. Source: Journal of the American College of Cardiology. 2000 March 1; 35(3): 706-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10716474&dopt=Abstract
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Correlates of health-related quality of life in patients with heart failure. Author(s): Westlake C, Dracup K, Creaser J, Livingston N, Heywood JT, Huiskes BL, Fonarow G, Hamilton M. Source: Heart & Lung : the Journal of Critical Care. 2002 March-April; 31(2): 85-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910383&dopt=Abstract
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Current role of beta-adrenergic blockers in the treatment of chronic congestive heart failure. Author(s): Smith AJ, Wehner JS, Manley HJ, Richardson AD, Beal J, Bryant PJ. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 January 15; 58(2): 140-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202537&dopt=Abstract
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Depression in patients with heart failure: physiologic effects, incidence, and relation to mortality. Author(s): Thomas SA, Friedmann E, Khatta M, Cook LK, Lann AL.
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Source: Aacn Clinical Issues. 2003 February; 14(1): 3-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574698&dopt=Abstract •
Dietary intake of various nutrients in older patients with congestive heart failure. Author(s): Gorelik O, Almoznino-Sarafian D, Feder I, Wachsman O, Alon I, Litvinjuk V, Roshovsky M, Modai D, Cohen N. Source: Cardiology. 2003; 99(4): 177-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845243&dopt=Abstract
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Do general practice patients with heart failure understand its nature and seriousness, and want improved information? Author(s): Buetow SA, Coster GD. Source: Patient Education and Counseling. 2001 December 1; 45(3): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722853&dopt=Abstract
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Doctors' perceptions of palliative care for heart failure: focus group study. Author(s): Hanratty B, Hibbert D, Mair F, May C, Ward C, Capewell S, Litva A, Corcoran G. Source: Bmj (Clinical Research Ed.). 2002 September 14; 325(7364): 581-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228136&dopt=Abstract
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Drug treatment in heart failure. Author(s): Lonn E, McKelvie R. Source: Bmj (Clinical Research Ed.). 2000 April 29; 320(7243): 1188-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784546&dopt=Abstract
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Effect of beta-blocker on left ventricular function and natriuretic peptides in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitor. Author(s): Hara Y, Hamada M, Shigematsu Y, Suzuki M, Kodama K, Kuwahara T, Hashida H, Ikeda S, Ohtsuka T, Hiasa G, Hiwada K. Source: Japanese Circulation Journal. 2000 May; 64(5): 365-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834452&dopt=Abstract
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Effect of biventricular pacing on myocardial glucose metabolism in patients with heart failure using fluoro-18-deoxyglucose positron emission tomography. Author(s): Ohkusu Y, Takahashi N, Ishikawa T, Sumita S, Kobayashi T, Matsushita K, Yamakawa Y, Uchino K, Kimura K, Inoue T, Umemura S. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 2): 144-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687800&dopt=Abstract
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Effect of carvedilol on microcirculatory and glucose metabolic regulation in patients with congestive heart failure secondary to ischemic cardiomyopathy. Author(s): Bottcher M, Refsgaard J, Gotzsche O, Andreasen F, Nielsen TT.
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Source: The American Journal of Cardiology. 2002 June 15; 89(12): 1388-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062733&dopt=Abstract •
Effect of metoprolol on absolute myocardial blood flow in patients with heart failure secondary to ischemic or nonischemic cardiomyopathy. Author(s): Bennett SK, Smith MF, Gottlieb SS, Fisher ML, Bacharach SL, Dilsizian V. Source: The American Journal of Cardiology. 2002 June 15; 89(12): 1431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062744&dopt=Abstract
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Effect of repeated sauna therapy on survival in TO-2 cardiomyopathic hamsters with heart failure. Author(s): Ikeda Y, Biro S, Kamogawa Y, Yoshifuku S, Kihara T, Minagoe S, Tei C. Source: The American Journal of Cardiology. 2002 August 1; 90(3): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127631&dopt=Abstract
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Effects of biventricular pacing on myocardial blood flow and oxygen consumption using carbon-11 acetate positron emission tomography in patients with heart failure. Author(s): Braunschweig F, Sorensen J, von Bibra H, Olsson A, Ryden L, Langstrom B, Linde C. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 95-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842260&dopt=Abstract
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Effects of direct mechanical ventricular assistance on regional myocardial function in an animal model of acute heart failure. Author(s): Kaczmarek I, Feindt P, Boeken U, Guerler S, Gams E. Source: Artificial Organs. 2003 March; 27(3): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662213&dopt=Abstract
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Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure. Author(s): Paterna S, Di Pasquale P, Parrinello G, Amato P, Cardinale A, Follone G, Giubilato A, Licata G. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2000 September; 2(3): 305-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10938493&dopt=Abstract
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Effects of long-term treatment with verapamil on left ventricular function and myocardial blood flow in patients with dilated cardiomyopathy without overt heart failure. Author(s): Neglia D, Sambuceti G, Giorgetti A, Bartoli M, Salvadori P, Sorace O, Puccini G, L'Abbate A, Parodi O.
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Source: Journal of Cardiovascular Pharmacology. 2000 December; 36(6): 744-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117374&dopt=Abstract •
Efficacy and safety of crataegus extract WS 1442 in comparison with placebo in patients with chronic stable New York Heart Association class-III heart failure. Author(s): Tauchert M. Source: American Heart Journal. 2002 May; 143(5): 910-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040357&dopt=Abstract
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Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Author(s): Ryden L, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Packer M, Poole-Wilson PA. Source: European Heart Journal. 2000 December; 21(23): 1967-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071803&dopt=Abstract
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Efficacy and safety of thermal vasodilation therapy by sauna in infants with severe congestive heart failure secondary to ventricular septal defect. Author(s): Sugahara Y, Ishii M, Muta H, Egami K, Akagi T, Matsuishi T. Source: The American Journal of Cardiology. 2003 July 1; 92(1): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842264&dopt=Abstract
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Electrical modulation of cardiac contractility: clinical aspects in congestive heart failure. Author(s): Pappone C, Vicedomini G, Salvati A, Meloni C, Haddad W, Aviv R, Mika Y, Darvish N, Kimchy Y, Shemer I, Snir Y, Pruchi D, Ben-Haim SA, Kronzon I. Source: Heart Failure Reviews. 2001 January; 6(1): 55-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248768&dopt=Abstract
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Exaggerated renal vasoconstriction during exercise in heart failure patients. Author(s): Middlekauff HR, Nitzsche EU, Hoh CK, Hamilton MA, Fonarow GC, Hage A, Moriguchi JD. Source: Circulation. 2000 February 22; 101(7): 784-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10683353&dopt=Abstract
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Exercise training in chronic heart failure: beneficial effects on cardiac (11)Chydroxyephedrine PET, autonomic nervous control, and ventricular repolarization. Author(s): Pietila M, Malminiemi K, Vesalainen R, Jartti T, Teras M, Nagren K, Lehikoinen P, Voipio-Pulkki LM.
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Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2002 June; 43(6): 773-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050322&dopt=Abstract •
Families dealing with advanced heart failure: a challenge and an opportunity. Author(s): Callahan HE. Source: Critical Care Nursing Quarterly. 2003 July-September; 26(3): 230-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930039&dopt=Abstract
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Gene therapy with adenovirus-mediated myocardial transfer of vascular endothelial growth factor 121 improves cardiac performance in a pacing model of congestive heart failure. Author(s): Leotta E, Patejunas G, Murphy G, Szokol J, McGregor L, Carbray J, Hamawy A, Winchester D, Hackett N, Crystal R, Rosengart T. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 June; 123(6): 1101-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063456&dopt=Abstract
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Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Author(s): Pittler MH, Schmidt K, Ernst E. Source: The American Journal of Medicine. 2003 June 1; 114(8): 665-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798455&dopt=Abstract
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Hawthorn extract improves chronic heart failure. Author(s): Eaton LJ, Kinkade S. Source: The Journal of Family Practice. 2003 October; 52(10): 753-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14529593&dopt=Abstract
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Heart failure in beta thalassemia: a 5-year follow-up study. Author(s): Kremastinos DT, Tsetsos GA, Tsiapras DP, Karavolias GK, Ladis VA, Kattamis CA. Source: The American Journal of Medicine. 2001 October 1; 111(5): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11583636&dopt=Abstract
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Hemodynamic management of congestive heart failure by means of a multiple mode rule-based control system using fuzzy logic. Author(s): Held CM, Roy RJ. Source: Ieee Transactions on Bio-Medical Engineering. 2000 January; 47(1): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10646286&dopt=Abstract
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Hibernating myocardium in post-ischaemic identification and revascularisation. Author(s): Pagano D.
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Source: Annals of the Royal College of Surgeons of England. 2000 July; 82(4): 236-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10932656&dopt=Abstract •
High resolution mapping of the pulmonary vein and the vein of Marshall during induced atrial fibrillation and atrial tachycardia in a canine model of pacing-induced congestive heart failure. Author(s): Okuyama Y, Miyauchi Y, Park AM, Hamabe A, Zhou S, Hayashi H, Miyauchi M, Omichi C, Pak HN, Brodsky LA, Mandel WJ, Fishbein MC, Karagueuzian HS, Chen PS. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 348-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875775&dopt=Abstract
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Hydrotherapy--a new approach to improve function in the older patient with chronic heart failure. Author(s): Cider A, Schaufelberger M, Sunnerhagen KS, Andersson B. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 August; 5(4): 527-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921815&dopt=Abstract
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Hypertrophic osteoarthropathy caused by PGE1 in a patient with congestive heart failure during cardiac rehabilitation. Author(s): Crevenna R, Quittan M, Hulsmann M, Wiesinger GF, Keilani MY, Kainberger F, Leitha T, Fialka-Moser V, Pacher R. Source: Wiener Klinische Wochenschrift. 2002 February 15; 114(3): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060968&dopt=Abstract
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Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. Author(s): Ceremuzynski L, Gebalska J, Wolk R, Makowska E. Source: Journal of Internal Medicine. 2000 January; 247(1): 78-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10672134&dopt=Abstract
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Images in congenital heart diseases. Documentation of decreased adrenergic receptors in left heart failure complicating aortic coarctation in infancy. Author(s): Fuse S, Tomita H, Hatakeyama K. Source: Cardiology in the Young. 2002 January; 12(1): 63-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922444&dopt=Abstract
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Implementation of a multidisciplinary disease management program for heart failure patients. Author(s): Riegel B, Thomason T, Carlson B, Bernasconi B, Clark A, Hoagland P, Liu P, Maringer D, Rizos A, Watkins J.
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Source: Congestive Heart Failure (Greenwich, Conn.). 1999 July-August; 5(4): 164-170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189308&dopt=Abstract •
Improving the quality of home care for patients with heart failure. Author(s): Gorski LA. Source: Caring. 2002 March; 21(3): 10-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912892&dopt=Abstract
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Injecting some hope. Cell therapy could lead to new treatments for congestive heart failure, whose sufferers now have few options. Author(s): Becker C. Source: Modern Healthcare. 2003 August 11; 33(32): 36-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12931539&dopt=Abstract
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Insulin resistance in chronic heart failure. Author(s): Coats AJ, Anker SD, Anker S. Source: Journal of Cardiovascular Pharmacology. 2000; 35(7 Suppl 4): S9-14. Review. Erratum In: J Cardiovasc Pharmacol 2001 September; 38(3): 490. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11346220&dopt=Abstract
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Magnetic resonance imaging in the assessment of patients with heart failure. Author(s): Prasad S, Pennell DJ. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2002 September-October; 9(5 Suppl): 60S-70S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271266&dopt=Abstract
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Malnutrition, muscle wasting and cachexia in chronic heart failure: the nutritional approach. Author(s): Pasini E, Aquilani R, Gheorghiade M, Dioguardi FS. Source: Ital Heart J. 2003 April; 4(4): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784775&dopt=Abstract
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Metabolic and clinical effects of oral magnesium supplementation in furosemidetreated patients with severe congestive heart failure. Author(s): Cohen N, Alon I, Almoznino-Sarafian D, Zaidenstein R, Weissgarten J, Gorelik O, Berman S, Modai D, Golik A. Source: Clin Cardiol. 2000 June; 23(6): 433-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10875034&dopt=Abstract
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Myoblast transplantation for heart failure. Author(s): Menasche P, Hagege AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin JT, Marolleau JP.
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Source: Lancet. 2001 January 27; 357(9252): 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214133&dopt=Abstract •
Myocardial efficiency during levosimendan infusion in congestive heart failure. Author(s): Ukkonen H, Saraste M, Akkila J, Knuuti J, Karanko M, Iida H, Lehikoinen P, Nagren K, Lehtonen L, Voipio-Pulkki LM. Source: Clinical Pharmacology and Therapeutics. 2000 November; 68(5): 522-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11103755&dopt=Abstract
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Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure. Author(s): Wallhaus TR, Taylor M, DeGrado TR, Russell DC, Stanko P, Nickles RJ, Stone CK. Source: Circulation. 2001 May 22; 103(20): 2441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11369683&dopt=Abstract
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Partnering for congestive heart failure: a clinic without walls. Author(s): Draus C, Walblay A, Barraco D, Hall D. Source: Outcomes Management. 2002 January-March; 6(1): 40-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500415&dopt=Abstract
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Pearls and pitfalls in the use and abuse of diuretics for chronic congestive heart failure. Author(s): Constant J. Source: Cardiology. 1999; 92(3): 156-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10754345&dopt=Abstract
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Peripheral and central ventilatory responses in central sleep apnea with and without congestive heart failure. Author(s): Solin P, Roebuck T, Johns DP, Walters EH, Naughton MT. Source: American Journal of Respiratory and Critical Care Medicine. 2000 December; 162(6): 2194-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11112137&dopt=Abstract
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Peripheral limitations of maximal aerobic capacity in patients with chronic heart failure. Author(s): Katz SD, Zheng H. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2002 March-April; 9(2): 215-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986567&dopt=Abstract
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Pilot study of guided imagery use in patients with severe heart failure. Author(s): Klaus L, Beniaminovitz A, Choi L, Greenfield F, Whitworth GC, Oz MC, Mancini DM. Source: The American Journal of Cardiology. 2000 July 1; 86(1): 101-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867104&dopt=Abstract
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Providing palliative care in end-stage heart failure. Author(s): Davies N, Curtis M. Source: Prof Nurse. 2000 March; 15(6): 389-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144184&dopt=Abstract
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Relationship between preoperative viability and postoperative improvement in LVEF and heart failure symptoms. Author(s): Bax JJ, Visser FC, Poldermans D, Elhendy A, Cornel JH, Boersma E, Valkema R, Van Lingen A, Fioretti PM, Visser CA. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 January; 42(1): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197985&dopt=Abstract
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Repeated sauna treatment improves vascular endothelial and cardiac function in patients with chronic heart failure. Author(s): Kihara T, Biro S, Imamura M, Yoshifuku S, Takasaki K, Ikeda Y, Otuji Y, Minagoe S, Toyama Y, Tei C. Source: Journal of the American College of Cardiology. 2002 March 6; 39(5): 754-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869837&dopt=Abstract
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Reverse remodeling and enhanced adrenergic reserve from passive external support in experimental dilated heart failure. Author(s): Saavedra WF, Tunin RS, Paolocci N, Mishima T, Suzuki G, Emala CW, Chaudhry PA, Anagnostopoulos P, Gupta RC, Sabbah HN, Kass DA. Source: Journal of the American College of Cardiology. 2002 June 19; 39(12): 2069-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084610&dopt=Abstract
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Role of spirituality in adjustment of patients with advanced heart failure. Author(s): Westlake C, Dracup K. Source: Progress in Cardiovascular Nursing. 2001 Summer; 16(3): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464434&dopt=Abstract
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Selective low-level leg muscle training alleviates dyspnea in patients with heart failure. Author(s): Beniaminovitz A, Lang CC, LaManca J, Mancini DM.
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Source: Journal of the American College of Cardiology. 2002 November 6; 40(9): 1602-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427412&dopt=Abstract •
Single photon emission computed tomography perfusion imaging for assessment of myocardial viability and management of heart failure. Author(s): Burrell S, Dorbala S, Di Carli MF. Source: Current Cardiology Reports. 2003 January; 5(1): 32-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493158&dopt=Abstract
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Slow breathing increases arterial baroreflex sensitivity in patients with chronic heart failure. Author(s): Bernardi L, Porta C, Spicuzza L, Bellwon J, Spadacini G, Frey AW, Yeung LY, Sanderson JE, Pedretti R, Tramarin R. Source: Circulation. 2002 January 15; 105(2): 143-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790690&dopt=Abstract
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Spirituality in persons with heart failure. Author(s): Beery TA, Baas LS, Fowler C, Allen G. Source: Journal of Holistic Nursing : Official Journal of the American Holistic Nurses' Association. 2002 March; 20(1): 5-25; Quiz 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898688&dopt=Abstract
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Surgical methods to reverse left ventricular remodeling in congestive heart failure. Author(s): Alfieri O, Maisano F, Schreuder JJ. Source: The American Journal of Cardiology. 2003 May 8; 91(9A): 81F-87F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729854&dopt=Abstract
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Survival and prognosis: investigation of Crataegus extract WS 1442 in congestive heart failure (SPICE)--rationale, study design and study protocol. Author(s): Holubarsch CJ, Colucci WS, Meinertz T, Gaus W, Tendera M. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2000 December; 2(4): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113721&dopt=Abstract
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T'ai Chi Chih as an intervention for heart failure. Author(s): Fontana JA, Colella C, Baas LS, Ghazi F. Source: Nurs Clin North Am. 2000 December; 35(4): 1031-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072287&dopt=Abstract
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The carvedilol hibernation reversible ischaemia trial, marker of success (CHRISTMAS) study. Methodology of a randomised, placebo controlled, multicentre study of carvedilol in hibernation and heart failure.
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Author(s): Pennell DJ, Ray SG, Davies G, Burgess M, Webster J, Slomka P, Atkinson P, Cleland JG. Source: International Journal of Cardiology. 2000 February 15; 72(3): 265-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10716137&dopt=Abstract •
The effect of specific inspiratory muscle training on the sensation of dyspnea and exercise tolerance in patients with congestive heart failure. Author(s): Weiner P, Waizman J, Magadle R, Berar-Yanay N, Pelled B. Source: Clin Cardiol. 1999 November; 22(11): 727-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554688&dopt=Abstract
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The hibernating heart: reversible left ventricular dysfunction in chronic heart failure. Author(s): Burn S, Walters M, Caplin J. Source: Postgraduate Medical Journal. 1999 July; 75(885): 419-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474727&dopt=Abstract
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The identification of myocardial hibernation in patients with ischemic heart failure by echocardiography and radionuclide studies. Author(s): Perrone-Filardi P, Chiariello M. Source: Progress in Cardiovascular Diseases. 2001 March-April; 43(5): 419-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251128&dopt=Abstract
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The management of heart failure--an overview. Author(s): Erdmann E. Source: Basic Research in Cardiology. 2000; 95 Suppl 1: I3-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192349&dopt=Abstract
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The muscle hypothesis: a model of chronic heart failure appropriate for osteopathic medicine. Author(s): Rogers FJ. Source: J Am Osteopath Assoc. 2001 October; 101(10): 576-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681164&dopt=Abstract
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The role of digitalis in the treatment of heart failure. Author(s): Demers C, McKelvie RS, Yusuf S. Source: Coronary Artery Disease. 1999 September; 10(6): 353-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474784&dopt=Abstract
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The thinking on TCM differential treatment of congestive heart failure. Author(s): Liang D, Zhang M.
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Source: J Tradit Chin Med. 2000 March; 20(1): 44-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10921172&dopt=Abstract •
Thermal hydrotherapy improves quality of life and hemodynamic function in patients with chronic heart failure. Author(s): Michalsen A, Ludtke R, Buhring M, Spahn G, Langhorst J, Dobos GJ. Source: American Heart Journal. 2003 October; 146(4): E11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564334&dopt=Abstract
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Thermal therapy for congestive heart failure: estimation by TEI index. Author(s): Tei C. Source: J Cardiol. 2001; 37 Suppl 1: 155-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11433821&dopt=Abstract
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Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Author(s): Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Mesquita CT, Rossi MI, Carvalho AC, Dutra HS, Dohmann HJ, Silva GV, Belem L, Vivacqua R, Rangel FO, Esporcatte R, Geng YJ, Vaughn WK, Assad JA, Mesquita ET, Willerson JT. Source: Circulation. 2003 May 13; 107(18): 2294-302. Epub 2003 April 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707230&dopt=Abstract
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Use of nonprescription medications by patients with congestive heart failure. Author(s): Ackman ML, Campbell JB, Buzak KA, Tsuyuki RT, Montague TJ, Teo KK. Source: The Annals of Pharmacotherapy. 1999 June; 33(6): 674-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10410177&dopt=Abstract
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Use of standard imaging techniques for prediction of postrevascularization functional recovery in patients with heart failure. Author(s): Marwick TH. Source: Journal of Cardiac Failure. 1999 December; 5(4): 334-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634675&dopt=Abstract
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What do patients know about their heart failure? Author(s): Artinian NT, Magnan M, Christian W, Lange MP. Source: Applied Nursing Research : Anr. 2002 November; 15(4): 200-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444578&dopt=Abstract
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What do we know about socioeconomic status and congestive heart failure? A review of the literature. Author(s): Blair AS, Lloyd-Williams F, Mair FS.
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Source: The Journal of Family Practice. 2002 February; 51(2): 169. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978216&dopt=Abstract •
When lymphoma and heart failure cross paths. Author(s): Nomiyama K, Shibuya T, Kataoka C, Aoki Y. Source: Journal of Hematotherapy & Stem Cell Research. 2003 February; 12(1): 7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662430&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 heart failure; 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 Age-Related Cognitive Decline Source: Healthnotes, Inc.; www.healthnotes.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com
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Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Cardiac Arrhythmia Source: Healthnotes, Inc.; www.healthnotes.com Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Cardiomyopathy Source: Prima Communications, Inc.www.personalhealthzone.com Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Congestive Heart Failure Source: Prima Communications, Inc.www.personalhealthzone.com Constipation Source: Integrative Medicine Communications; www.drkoop.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Edema Source: Healthnotes, Inc.; www.healthnotes.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com
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Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypothermia Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com TIAs Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Colon Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,682,00.html Naturopathy Source: Integrative Medicine Communications; www.drkoop.com
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Chinese Medicine Renshen Alternative names: Ginseng Leaf; Renshenye (Ren Shen Ye); Folium Ginseng Source: Chinese Materia Medica
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Herbs and Supplements Alpha2-adrenergic Agonists Source: Integrative Medicine Communications; www.drkoop.com Amiloride Source: Healthnotes, Inc.; www.healthnotes.com Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Arginine Source: Healthnotes, Inc.; www.healthnotes.com
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Arginine Source: Prima Communications, Inc.www.personalhealthzone.com Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Astragalus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Astragalus Membranaceus Source: Integrative Medicine Communications; www.drkoop.com Astragalus Mongholicus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Baking Soda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,835,00.html Beta-blockers Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: Prima Communications, Inc.www.personalhealthzone.com Blue Cohosh Alternative names: Caulophyllum thalictroides Source: Healthnotes, Inc.; www.healthnotes.com Captopril Source: Healthnotes, Inc.; www.healthnotes.com Cardiac Glycosides Source: Integrative Medicine Communications; www.drkoop.com Carvedilol Source: Healthnotes, Inc.; www.healthnotes.com Caulophyllum Alternative names: Blue Cohosh; Caulophyllum thalictroides (MICH.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Coenzyme Q Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,768,00.html Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Coenzyme Q10 (CoQ10) Source: Prima Communications, Inc.www.personalhealthzone.com Coleus Alternative names: Coleus forskohlii Source: Healthnotes, Inc.; www.healthnotes.com CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Crataegus Laevigata Source: Integrative Medicine Communications; www.drkoop.com Crataegus Monogyna Source: Integrative Medicine Communications; www.drkoop.com Dandelion Alternative names: Taraxacum officinale Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone (dhea) Source: Healthnotes, Inc.; www.healthnotes.com Digoxin Source: Healthnotes, Inc.; www.healthnotes.com Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Enalapril Source: Healthnotes, Inc.; www.healthnotes.com Ephedra Source: Healthnotes, Inc.; www.healthnotes.com Felodipine Source: Healthnotes, Inc.; www.healthnotes.com
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Fibric Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hawthorn Alternative names: Crataegus laevigata, Crataegus oxyacantha, Crataegus monogyna Source: Healthnotes, Inc.; www.healthnotes.com Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Hawthorn Source: Prima Communications, Inc.www.personalhealthzone.com Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html Huang-qi Source: Integrative Medicine Communications; www.drkoop.com Indapamide Source: Healthnotes, Inc.; www.healthnotes.com Isosorbide Dinitrate Source: Healthnotes, Inc.; www.healthnotes.com Juniper Berry Source: Prima Communications, Inc.www.personalhealthzone.com Lisinopril Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Loop Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com
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Nitroglycerin Source: Healthnotes, Inc.; www.healthnotes.com Oregano/Wild Marjoram Alternative names: Origanum vulgare Source: Healthnotes, Inc.; www.healthnotes.com Panax Ginseng Source: Integrative Medicine Communications; www.drkoop.com Phenothiazine Derivatives Source: Integrative Medicine Communications; www.drkoop.com Prazosin Source: Healthnotes, Inc.; www.healthnotes.com Quinapril Source: Healthnotes, Inc.; www.healthnotes.com Ramipril Source: Healthnotes, Inc.; www.healthnotes.com Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sulfonylureas Source: Integrative Medicine Communications; www.drkoop.com Taraxacum Officinale Source: Integrative Medicine Communications; www.drkoop.com Taurine Source: Healthnotes, Inc.; www.healthnotes.com Taurine Source: Prima Communications, Inc.www.personalhealthzone.com Terazosin Source: Healthnotes, Inc.; www.healthnotes.com Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thiazide Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com
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Thioxanthene Derivatives Source: Integrative Medicine Communications; www.drkoop.com Triamterene Source: Healthnotes, Inc.; www.healthnotes.com Tricyclic Antidepressants (tcas) Source: Integrative Medicine Communications; www.drkoop.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON HEART FAILURE Overview In this chapter, we will give you a bibliography on recent dissertations relating to heart failure. 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 “heart failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on heart failure, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Heart Failure 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 heart failure. 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: •
A Study in Predicting Oxygen Consumption in Older Women with Diastolic Heart Failure by Al-Nsair, Nezam A.; PhD from University of Cincinnati, 2003, 137 pages http://wwwlib.umi.com/dissertations/fullcit/3084729
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Atrial Remodeling in Congestive Heart Failure by Khan, Anjum Hafeez; MSC from University of Toronto (Canada), 2002, 113 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74107
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Calcium Transport by Mitochondria and Microsomes in Different Types of Heart Failure by Lee, Sheu Lun; PhD from The University of Manitoba (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20869
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Diastolic Dysfunction in Patients Enrolled in a Heart Failure Disease Management Program by Gowenlock, Linda Susan; MSN from The University of Texas Health Science Center at San Antonio, 2002, 55 pages http://wwwlib.umi.com/dissertations/fullcit/1410188
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Does Mutual Goal Setting Make a Difference in Level of Self-efficacy for Patients with Congestive Heart Failure Receiving Home Care by Rogers, Avis Anne; MSN from Grand Valley State University, 2002, 72 pages http://wwwlib.umi.com/dissertations/fullcit/1406254
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Factors Influencing Adherence to a Prescribed Health Regimen for Individuals with Heart Failure by Scotto, Carol J.; PhD from Duquesne University School of Nursing, 2003, 110 pages http://wwwlib.umi.com/dissertations/fullcit/3085111
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Health Promotion Behaviors of Rural Women with Heart Failure by Pierce, Carolyn S.; DSN from the University of Alabama at Birmingham, 2002, 154 pages http://wwwlib.umi.com/dissertations/fullcit/3066336
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Learning Needs As Perceived by Heart Failure Patients in Postdischarge Settings by Clark, Judith C.; MSN from Eastern Michigan University, 2002, 64 pages http://wwwlib.umi.com/dissertations/fullcit/1408039
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Long-term Outcomes of a Multidisciplinary Hospital-based Wellness Program Designed for Patients with Congestive Heart Failure; Increasing Their Quality of Life While Reducing Hospitalization by Brubaker, Craig Robert; PhD from University of Central Florida, 2002, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3069435
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Myocardial High-energy Phosphate Metabolism and Creatine Kinase Alterations in Hearts with Congestive Heart Failure by Ye, Yun; PhD from University of Minnesota, 2002, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3069216
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Myosin Kinetics in Congestive Heart Failure in the Rat by Elkassem, Samer; MSC from University of Calgary (Canada), 2002, 187 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76210
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Outcomes of Home Management Methods for Chronic Heart Failure by Bondmass, Mary D.; PhD from University of Illinois at Chicago, Health Sciences Center, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3058231
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Perceived Knowledge of Heart Failure and Adherence to Self-care Recommendations by Van Ess, Cheryl Lynn; MSN from Grand Valley State University, 2002, 64 pages http://wwwlib.umi.com/dissertations/fullcit/1407902
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Personal and Situational Factors Influencing Coping and Depression in Adults with Heart Failure by Vollman, Michael William; PhD from Vanderbilt University, 2003, 92 pages http://wwwlib.umi.com/dissertations/fullcit/3085805
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Pharmaceutical Care of Patients with Congestive Heart Failure by Sadik, Adel Shatan; PhD from Queen's University of Belfast (Northern Ireland), 2002 http://wwwlib.umi.com/dissertations/fullcit/f745057
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Potential Factors Contributing to Diaphragm Myopathy in Congestive Heart Failure by Dominguez, Jesus Felipe; PhD from University of Southern California, 2002, 109 pages http://wwwlib.umi.com/dissertations/fullcit/3073770
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Relationship between Home Health Service Utilization and Functional Status of Medicare Patients with Heart Failure by Piyabanditkul, Lukawee; PhD from University of Kentucky, 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3092323
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Studies on the Renin Angiotensin System in Human and Dog with Special Reference to Primary Aldosteronism and Heart Failure by Granger, Pierre; Advdeg from McGill University (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK03958
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The Ability of Paramedics to Identify Congestive Heart Failure in the Prehospital Setting by Drake, James William; MS from the University of Mississippi Medical Center, 2002, 97 pages http://wwwlib.umi.com/dissertations/fullcit/1408841
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The Effect of Practical Education Programming for the Elderly (pepe) on the Rehospitalization Rate of Older Congestive Heart Failure Patients: a Quasi Experimental Study (older Patients) by Donlon, Barbara Cole, EDD from The University of Southern Mississippi, 1993, 157 pages http://wwwlib.umi.com/dissertations/fullcit/9402525
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The Effect of Supportive Education, As a Tertiary Nursing Intervention, on the Quality of Life of Patients with Heart Failure by Switek, Julie Anne; Msn from Grand Valley State University, 2002, 81 pages http://wwwlib.umi.com/dissertations/fullcit/1411254
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The Effect of Supportive-educative Nursing Interventions on the Hospital Readmission Rates of Patients with Heart Failure by Whitaker, Patrice Marie; MSN from Grand Valley State University, 2002, 83 pages http://wwwlib.umi.com/dissertations/fullcit/1406877
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The Effect on Re-hospitalization of an Education/surveillance Program on Patients with Functional Class Ii and Iii Congestive Heart Failure by Munoz, Miguel; PhD from the University of New Mexico, 2002, 86 pages http://wwwlib.umi.com/dissertations/fullcit/3041973
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The Effectiveness of a Home-based Exercise Program in Older Women with Diastolic Heart Failure by Gary, Rebecca Ann; PhD from the University of North Carolina at Chapel Hill, 2003, 304 pages http://wwwlib.umi.com/dissertations/fullcit/3086536
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The Effects of a Clinical Pathway on Hospitalized Heart Failure Patients by Halloran, Teresa Heise; PhD from University of Missouri - Saint Louis, 2002, 236 pages http://wwwlib.umi.com/dissertations/fullcit/3031622
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The Effects of a Diuretic Titration Protocol on Clinical Outcomes in Heart Failure Patients by Prasun, Marilyn Alice; PhD from University of Illinois at Chicago, Health Sciences Center, 2002, 142 pages http://wwwlib.umi.com/dissertations/fullcit/3058237
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The Lived Experience of a Small Number of Wives Caring for a Husband with Heart Failure by Weller Moore, Rhonda M.; PhD from New York University, 2002, 326 pages http://wwwlib.umi.com/dissertations/fullcit/3031322
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The Meaning of Social Support: the Perspective of Arab Canadians with Congestive Heart Failure by Debs-Ivall, Salma; MSC from University of Ottawa (Canada), 2002, 162 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76573
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The Medical Interaction and Treatment Outcomes for Patients with Congestive Heart Failure by Charous, Margaret A., PhD from Marquette University, 1997, 129 pages http://wwwlib.umi.com/dissertations/fullcit/9811381
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The Relationship between Quality of Life and Social Support in Congestive Heart Failure Patients by Hulbert, Janet E.; MS from University of Alaska Anchorage, 2002, 90 pages http://wwwlib.umi.com/dissertations/fullcit/1409950
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The Relationship of Health Locus of Control and Health-promoting Behaviors in the Newly Diagnosed Congestive Heart Failure Patient by Hardin, Patricia H.; MSN from Texas Tech University, 2002, 96 pages http://wwwlib.umi.com/dissertations/fullcit/1408330
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The Role of Signal Transduction Pathways in Cardiac Hypertrophy and Heart Failure by Antos, Christopher Lee; PhD from The University of Texas Southwestern Medical Center at Dallas, 2003 http://wwwlib.umi.com/dissertations/fullcit/f16593
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Transmural Heterogeneities of Repolarization and Arrhythmogenesis in the Long Qt Syndrome and Congestive Heart Failure by Akar, Fadi Gabriel; PhD from Case Western Reserve University, 2002, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3052268
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Using Self-efficacy Theory to Educate Heart Failure Patients on Home Self-weighing by Hoke, Linda Marie; PhD from Temple University, 2002, 103 pages http://wwwlib.umi.com/dissertations/fullcit/3079118
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 HEART FAILURE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning heart failure.
Recent Trials on Heart Failure The following is a list of recent trials dedicated to heart failure.5 Further information on a trial is available at the Web site indicated. •
Acupuncture in Cardiovascular Disease Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to determine if acupuncture decreases adrenaline levels in heart failure, thereby potentially improving survival and quality of life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032422
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African-American Heart Failure Trial Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): Nitromed Purpose - Excerpt: A placebo-controlled trial of BiDil added to standard therapy in African-American patients with heart failure.
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These are listed at www.ClinicalTrials.gov.
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Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047775 •
Efficacy and Cost Effectiveness of Relaxation and Response to CHF Condition(s): Heart Failure, Congestive 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: Chronic heart failure (CHF) is a prevalent and costly disease. Because the incidence is higher among the elderly, the number of CHF patients is expected to rise as the population ages. Despite the development of significant pharmaceutical treatments, morbidity and mortality of CHF patients remain high, patients? quality of life is poor, and their health care utilization is heavy. Exercise training and biobehavioral interventions have been suggested as adjuvant therapy to drug protocols. Among biobehavioral interventions, the relaxation response has been found to be effective in managing CHF-related conditions such as hypertension and coronary artery disease. The relaxation response is a state in which individuals evoke a bodily calm that has the opposite effect of the fight-or-flight response, with concomitant favorable physiological changes that are likely to reduce symptoms and improve the quality of life of CHF patients. Hence, it may lead to lower health care utilization and reduce costs. The study?s objectives are: 1. To evaluate the effects of a 15-week relaxation response intervention program on improving functional capacity and healthrelated quality of life as compared with an on-going 15-week educational program for cardiac disease management, and a control group of usual cardiac care; 2. To identify the costs of conducting the relaxation response intervention and the program of cardiac care education, as well as the costs associated with utilization of cardiac care services for patients in each of the three study groups; and to compare cost among three study groups adjusting for patient characteristics. We propose to conduct a single-blind threearmed randomized trial to evaluate the efficacy and cost of the relaxation response in CHF patients at the VA. Two types of control groups will be used in this trial: an educational program and a usual care group. The trial will be conducted in 120 ambulatory CHF patients who receive health care at the Boston and West Roxbury VA medical centers. Patients will be randomly assigned, with equal numbers, to one of the three study groups. Outcomes include cardiac functional capacity and health-related quality of life to be reported by the patients. These measures will be administered to all 120 patients at baseline, at the end of the 15-week intervention, and at 6 and 12-month follow-up. We will collect information on costs associated with the intervention and control programs, estimate costs for health services utilization by patients, and conduct cost analyses. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012818
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ESSENTIAL-"The Studies of Oral Enoximone Therapy in Advanced Heart Failure" Condition(s): Heart Failure, Congestive
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Study Status: This study is currently recruiting patients. Sponsor(s): Myogen Purpose - Excerpt: To determine if low-dose enoximone therapy is an effective treatment for advanced chronic heart failure. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051285 •
Evaluating Telehealth Home Care for Elderly Veterans with Congestive Heart Failure Condition(s): Heart Failure, Congestive Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Purpose - Excerpt: Congestive heart failure (CHF) is one of the most common reasons for hospitalization in patients aged 65 years and older. Many hospitalizations for CHF are potentially preventable if the warning signs of decompensation are recognized and treated before the situation becomes emergent. Home-based intervention programs have reduced unplanned readmission rates for patients with CHF by up to 50 percent. Using advanced telecommunications technologies it is now possible to provide greatly improved access and availability of services in a more timely and cost effective manner directly to patients' homes. Although telehealth offers a number of theoretical advantages, few empirical studies have compared telehealth to traditional delivery modes, and virtually no studies have compared the effectiveness of alternative telehealth applications. The purpose of this study is to compare the effectiveness and resource use of two telehealth interventions to traditional care provided for recently discharged outpatients with CHF. Four hypotheses will be tested. Compared to subjects who receive usual care, subjects who receive telehealth interventions (telephone or interactive video) following discharge will: 1) have lower readmission rates; 2) report improved quality of life, self-efficacy, and satisfaction with care; 3) use fewer resources, including hospital days, urgent care visits, and telephone calls; and 4) have higher survival rates. The study is a randomized controlled clinical trial. We will compare usual care to an intervention delivered by either telephone or interactive video to veterans following discharge from the hospital. A total of 198 subjects will be enrolled over three years. Subjects in the treatment groups (telephone or interactive video) will receive the intervention for 90 days following discharge from the hospital. Data to be collected includes measures of quality of life, self-efficacy, satisfaction, resource use, and mortality. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057200
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Evaluation of Intravenous Levosimendan Efficacy in the Short Term Treatment of Decompensated Chronic Heart Failure. Condition(s): Heart Failure, Congestive Study Status: This study is currently recruiting patients.
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Sponsor(s): Orion Pharma Purpose - Excerpt: The purpose of this study is to evaluate the efficacy of a 24-hour infusion of levosimendan compared with placebo in the treatment of decompensated chronic heart failure. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00048425 •
Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) Condition(s): Heart Diseases; Heart Failure, Congestive; Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare the efficacy of Pulmonary Artery Catheterization (PAC)directed treatment strategy to a non-invasive treatment strategy on morbidity and mortality in patients with severe, class IV New York Heart Association (NYHA) congestive heart failure. A secondary objective is to determine costs and resource utilization of PAC-directed treatment strategy compared to non-invasive treatment strategy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000619
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EVEREST: Efficacy of Vasopressin antagonism in hEart failuRE: outcome Study with Tolvaptan Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): Otsuka Maryland Research Institute Purpose - Excerpt: The purpose of this study is to compare the effectiveness of tolvaptan or placebo in adults with worsening congestive heart failure (CHF). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071331
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Heart Failure Adherence and Retention Trial (HART) Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Congestive Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)
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Purpose - Excerpt: To test whether a self-management (SM) intervention, compared to usual care, will reduce the risk for adverse clinical outcome in patients with mild to moderate heart failure. Phase(s): Phase III Study Type: Interventional Contact(s): Lynda Powell (312) 942-2013
[email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00018005 •
Heart Failure and Anemia Condition(s): Heart Failure; Anemia Study Status: This study is currently recruiting patients. Sponsor(s): Amgen Purpose - Excerpt: This study evaluates the safety and efficacy of darbepoetin alfa to treat anemia in subjects with heart failure of NYHA class 2 to 4. The study assesses the effect of the treatment on exercise capacity and heart failure symptoms. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049985
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Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the long-term safety and effectiveness of exercise training for congestive heart failure patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047437
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Multicenter, Randomized, Double-Blind, Placebo Controlled, Efficacy Study on the Effects of Tolvaptan on Left Ventricular Dilatation in Congestive Heart Failure Patients Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): Otsuka Maryland Research Institute Purpose - Excerpt: The purpose of this study is to study the effects of tolvaptan on the size and function of the left heart chamber (ventricle) in patients with congestive heart failure (CHF) Phase(s): Phase II Study Type: Interventional Contact(s): Patty Wedge 617-636-5068
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Web Site: http://clinicaltrials.gov/ct/show/NCT00043758 •
MYOHEART(tm) (Myogenesis Heart Efficiency and Regeneration Trial) Condition(s): Congestive Heart Failure; Coronary Artery Disease; Myocardial Infarction Study Status: This study is currently recruiting patients. Sponsor(s): Bioheart, Inc. Purpose - Excerpt: The MyoCell(tm) implantation using the MyoCath(tm) delivery catheter system may have the potential to add a new dimension to the management of post-infarct deterioration of cardiac function in subjects with congestive heart failure. Based on pre-clinical studies, implantation of autologous skeletal myoblasts may lead to replacement of non-functioning myocardial scar with functioning muscle and improvement in myocardial performance. Preliminary data in human subjects suggest skeletal myoblast implantation at the time of CABG may lead to the same effects. In principal, myoblast implantation by catheter delivery may offer the same therapeutic benefit. The present clinical study is to be conducted primarily to evaluate the safety of MyoCell(tm) implantation using the MyoCath(tm) delivery system and secondarily to evaluate the effect on regional myocardial function post treatment. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054678
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Occluded Artery Trial (OAT) Condition(s): Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Heart Failure, Congestive; Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether opening an occluded infarcted artery 3-28 days after an acute myocardial infarction in high-risk asymptomatic patients reduces the composite endpoint of mortality, recurrent myocardial infarction, and hospitalization for class IV congestive heart failure over a three year follow-up. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004562
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Oxypurinol compared with Placebo for Class III-IV NYHA Congestive Heart Failure Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): Cardiome Pharma Purpose - Excerpt: The OPT-CHF (OxyPurinol Therapy for CHF) study is designed to demonstrate the efficacy and safety of oral oxypurinol vs. placebo in a randomized, double-blind, twenty-four week trial in 400 patients in up to 50 centers. Measures of
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clinical efficacy (NYHA class and Patient Global Assessment) as well as clinical outcomes (e.g., death, worsening heart failure, and hospitalization) will be assessed as a composite endpoint in this trial. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063687 •
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 Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057057
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Rosiglitazone to Treat Patients with Heart Failure and Glucose Intolerance or Type II Diabetes Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients.
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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will evaluate the safety and effectiveness of the drug rosiglitazone for improving heart function in patients with heart failure and glucose intolerance or type II (adult-onset) diabetes, or both. Because of a lowered sensitivity to the hormone insulin, patients with type II diabetes or glucose-intolerance do not regulate glucose (sugar) effectively. Rosiglitazone is used to treat type II diabetes, but it is not commonly given to patients with heart failure because it can cause leg swelling and, rarely, pulmonary edema. However, patients with heart failure who also have glucose intolerance or type II diabetes generally fare worse than those with heart failure alone, and therapies that decrease insulin resistance may be beneficial to these patients. Patients 21 years of age and older with heart failure and type II diabetes or glucose intolerance, or both, may be eligible for this study. Patients must be stable on current therapy for heart failure and must not have any planned surgeries for coronary artery disease. Candidates will be admitted to the NIH Clinical Center for from 2 to 7 days for screening procedures, which include a medical history and physical examination, blood and urine tests, electrocardiogram (ECG), chest x-ray, magnetic resonance imaging (MRI), exercise testing, and echocardiography (ultrasound test of the heart). Participants will be randomly assigned to receive either rosiglitazone or placebo (an identicallooking pill with no active ingredient). They will take one tablet a day for the first month, one tablet twice a day for the second month, and then two tablets twice a day from the third month to the end of the study at 6 months. During the treatment period, patients will have a history, physical examination, and blood tests every 4 weeks, exercise testing and echocardiography at 3 and 6 months, and urinalysis, electrocardiogram and MRI at 6 months. To check for fluid accumulation in the legs or lungs, patients will report their weight and symptoms every 2 weeks throughout the study. After the 6-month treatment period, patients will be put back on the diabetes medicines they were taking before the study. Their physicians will be notified of possible modifications in treatment for maintaining optimum glucose tolerance. Six months after completing treatment (one year after beginning the study), patients will return to the Clinical Center for blood tests to measure the long-term effects of rosiglitazone and to evaluate progress. They will then be invited to return to the clinic for annual checkups, if possible, or for yearly follow-up by mail or telephone to review their health status. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064727 •
Safety and Efficacy Study of carvedilol to treat children with congestive heart failure Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): Shaddy, Robert, M.D.; University of Utah; Sponsor Name Pending Purpose - Excerpt: The purpose of this study is to determine whether a new medicine, called carvedilol, improves symptoms and heart function in children who have congestive heart failure (diminished function of their heart muscle that pumps blood to the body). To accomplish this, we will give carvedilol to some patients who have diminished heart function and congestive heart failure and see whether symptoms and heart function are better at the end of an 8 month period in those who received
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carvedilol compared to the other patients who did not receive carvedilol. We will be testing 2 different doses of carvedilol compared to no additional medicine. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052026 •
Safety and efficacy study of the vasopressin receptor antagonist conivaptan in patients with acute decompensated heart failure Condition(s): Congestive Heart Failure Study Status: This study is currently recruiting patients. Sponsor(s): Yamanouchi Pharma America Purpose - Excerpt: This is a randomized, double-blind, placebo-controlled, dose ranging pilot study to examine the effects of conivaptan in patients with acute decompensated heart failure. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00057356
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Surgical Treatment for Ischemic Heart Failure (STICH) Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Failure; Heart Failure, Congestive; Heart Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare medical therapy with coronary bypass surgery and/or surgical ventricular restoration for patients with congestive heart failure and coronary heart disease. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023595
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The safety and efficacy of adjunct carvedilol in children with moderate heart failure Condition(s): Heart Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: We would like to see if using Carvedilol in adjunct with Ace inhibitors will increase ejection fraction of the heart under echo. All interpretation of data will be sent to Boston Children's Hospital to be reviewed, which is the primary research center in this study. There are 5 hospitals participating in this study. The population targeted are children with moderate heart failure and must be on Ace inhibitors at the time of enrollment. Our outcome after placing them on Carvedilol is to change their ejection fraction on echo. The patients will be seen every 1-2 weeks, while
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we will titrate their medication to a maintenance dose. Secondary outcome is to increase quality of life, exercise tolerance and decrease their symptom scores as noted on their questionnaires. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004854 •
ESCAPE Mechanistic Substudies - Ancillary to ESCAPE Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Congestive Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the value of serum markers as surrogate endpoints and hemodynamic biomarkers of congestive heart failure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021957
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Heart Failure in the Community Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure; Coronary Disease; Diabetes Mellitus; Hypertension; Obesity Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To monitor trends in congestive heart failure in Olmsted County, Minnesota. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053534
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Management of Patients with Congestive Heart Failure After Hospitalization Condition(s): Heart Failure, Congestive Study Status: This study is no longer recruiting patients. Sponsor(s): Scios Purpose - Excerpt: The objective of this study is to assess the safety and tolerability of different doses of Natrecor(r) when administered serially to patients with decompensated CHF who are concomitantly receiving their usual cardiac medications and are at high risk for hospitalization. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040612
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Monitoring Community Trends in Heart Failure Condition(s): Cardiovascular Diseases; Heart Failure, Congestive; Heart Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine temporal trends from 1995 and 2000 in the incidence rates of heart failure, its therapeutic management, and changes over time in the hospital and long-term survival of patients with heart failure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035724
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Phase II Safety, Efficacy and Tolerability Study of MCC135 in Subjects with Congestive Heart Failure, NYHA Class II/III Condition(s): Congestive Heart Failure Study Status: This study is no longer recruiting patients. Sponsor(s): Takeda Pharmaceuticals Purpose - Excerpt: This drug is being developed for treatment of congestive heart failure. The study is designed to determine the effect of 2 different doses and two different regimens of MCC-135 on the disease state and Quality of Life. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050076
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Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Congestive Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a randomized, unblinded clinical trial comparing the left ventricular assist device (LVAD) with maximum medical management in patients with end-stage heart failure who are not candidates for heart transplantation. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000607
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Reversal of Ventricular Remodeling with Toprol-XL Condition(s): Heart Failure, Congestive Study Status: This study is no longer recruiting patients. Sponsor(s): AstraZeneca
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Purpose - Excerpt: The purpose of this study is to determine whether treatment with Toprol-XL for 12 months in asymptomatic heart failure subjects will improve their heart structure and thus prevent the progression to symptomatic disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00038077 •
Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Condition(s): Arrhythmia; Cardiovascular Diseases; Death, Sudden, Cardiac; Heart Diseases; Heart Failure, Congestive; Heart Failure Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare conventional treatment of congestive heart failure (CHF) with two experimental interventions: amiodarone and an implantable cardioverterdefibrillator (ICD). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000609
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The DIAMOND Study: Distensibility Improvement And Remodeling in Diastolic Heart Failure Condition(s): Heart Failure, Congestive; Dyspnea; Pulmonary Edema Study Status: This study is no longer recruiting patients. Sponsor(s): Alteon Inc. Purpose - Excerpt: The purpose of this study is to test the hypothesis that treatment with oral ALT-711 twice daily for 16 weeks will improve aortic distensibility, exercise tolerance, and quality of life in elderly patients with isolated diastolic heart failure (DHF), and that the improvements in exercise tolerance will correlate with the improvements in aortic distensibility. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043836
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Ventricular Matrix Remodeling: Correlates and Prognosis Condition(s): Heart Diseases; Heart Failure, Congestive; Cardiovascular Diseases; Heart Failure Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)
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Purpose - Excerpt: To assess the diagnostic and prognostic usefulness of serum markers of left ventricular remodeling for predicting congestive heart failure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021892 •
A Thyroid Analog to Treat Heart Failure: Phase II Trial Condition(s): Congestive Heart Failure Study Status: This study is not yet open for patient recruitment. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: Congestive heart failure (CHF) affects 4-5 million Americans, and its prevalence is predicted to increase over the next few decades. Thryoid hormone has unique actions which make it a novel and potentially useful agent for treatment of CHF. Due to possible adverse affects of thyroid hormone, there is interest in developing analogs with fewer undesirable side effects. 3,5- diiodothyropropionic acid (DITPA) has been shown to improve diastolic function in both animal models and a recently completed double-blind placebo controlled trial in 19 humans. The goal of the proposed Phase II study is to show safety and demonstrate a medication of efficacy of DITPA needed in patients with CHF. This study is a prerequisite for a larger Phase III trial which would determine whether mortality is improved with DITPA. To better define the appropriate doses, prior to the Phase II study we will also conduct an initial pharmacokinetic study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032643
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Autologous Cultured Myoblasts (BioWhittaker) Transplanted via Myocardial Injection Condition(s): Congestive Heart Failure; Coronary Artery Disease; Myocardial Infarction Study Status: This study is not yet open for patient recruitment. Sponsor(s): Bioheart, Inc. Purpose - Excerpt: MyoCell(tm) implantation by epicardial injection during CABG surgery has the potential to add a new dimension to the management of post-infarct deterioration of cardiac function. Based on existing non-clinical studies and clinical reports, implantation of autologous skeletal myoblasts appears to lead to the replacement of non-functioning myocardial scar with functioning muscle and appears to improve myocardial performance relative to case without myoblast implantation. In a few investigational patients, myoblast implantation can be, and has been, done in conjunction with CABG and appears to have the potential to provide for additive treatment during surgery. The present study is being conducted to evaluate more fully the safety of MyoCell(tm) implantation via epicardial injection during CABG surgery and its effect on regional myocardial function. Phase(s): Phase I
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050765 •
Beta-Blocker Evaluation in Survival Trial (BEST) Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive; Heart Failure Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if addition of a beta-blocker to standard therapy in Class III and Class IV heart failure patients reduced total mortality. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000560
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Community Surveillance of Congestive Heart Failure Condition(s): Cardiovascular Diseases; Heart Failure, Congestive; Heart Diseases; Heart Failure Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a surveillance study of congestive heart failure (CHF). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005517
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Computerized Guidelines Enhanced by Symptoms and History: Clinical Effects Condition(s): Heart Failure, 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: Physician compliance with practice guidelines is imperfect. Computer-generated reminders from electronic medical record systems have been shown to increase compliance with guidelines, but they often require symptom and history data, which limits computer facilitation. Heart failure is a serious condition for which compliance with established guidelines is suboptimal. Physicians' compliance with heart failure guidelines may improve if computer-generated reminders use symptom and history data. (1) Program standard computer-based guidelines for heart failure using data from the electronic medical record systems at the Indianapolis and Seattle VAMCs. (2) Establish a system for capturing data on symptoms and history from heart failure patients before scheduled primary care visits. (3) Incorporate these data into enhanced computer reminders. (4) Conduct a randomized, controlled trial comparing these two types of reminders' effects on physician prescribing, patient
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objective and subjective outcomes, and health care utilization. This controlled trial targets patients with objective evidence of left ventricular dysfunction on cardiac imaging studies and a current outpatient diagnosis of heart failure. Primary care physicians in the Indianapolis and Seattle VAMCs have been randomized to receive either standard heart failure treatment reminders or reminders enhanced by history/symptom data. Study data come from the VAMCs electronic medical record systems (i.e., clinical data, utilization, and costs) and patient interviews (heart failure symptoms and medication compliance, heart failure-specific quality of life, and patients' satisfaction with their primary care). Data analysis will be performed at the patient level using general estimating equations to account for patient and physician characteristics and clustering of patients within physicians. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013039 •
Congestive Heart Failure Trends in the Elderly 1970-94 Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive; Heart Failure Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate trends in the incidence and survival rates of congestive heart failure (CHF) in two successive cohorts of elderly people (1970-74, 1990-94) in a health maintenance organization (HMO). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005499
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Digitalis Investigation Group (DIG) Condition(s): Arrhythmia; Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive; Sinus Arrhythmia; Heart Failure Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if digitalis had a beneficial, harmful, or no effect on total mortality in patients with clinical heart failure and sinus rhythm. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000476
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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
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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 Web Site: http://clinicaltrials.gov/ct/show/NCT00012870 •
Estrogen, Cytokines and Heart Failure in Wome Condition(s): Cardiovascular Diseases; Heart Failure, Congestive; Heart Diseases; Menopause Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effects of estrogen therapy on postmenopausal women with congestive heart failure. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041431
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Exercise Effect on Aerobic Capacity and Quality of Life in Heart Failure Condition(s): Heart Failure, Congestive Study Status: This study is completed.
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Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: Chronic heart failure (HF) is a syndrome of impaired ventricular function resulting in clinical symptoms of fatigue, dyspnea, and decreased exercise capacity. These symptoms lead to a cyclical pattern of an increasing sedentary lifestyle with accompanying deconditioning and deterioration of muscle function. Until recently, the prescription for individuals with HF was rest and minimization of physical exertion. The primary objectives of this randomized clinical trial were to determine whether subjects, with moderate to severe chronic HF, who completed a 12-week individualized program of cardiopulmonary training (exercise group) would have significantly greater (i) quality of life, measured by the Rand Short Form-36, and (ii) aerobic fitness, measured by oxygen uptake during symptom limited maximal metabolic treadmill testing, than subjects who met weekly with an investigator and received vital sign measurements (non-exercise group). A randomized controlled clinical trial was utilized. Individuals who met the inclusion criteria were randomly assigned to either an exercise or control group. Individuals in the exercise group received 36 weeks of exercise training (primary outcome variables were measured at 12 weeks). Participants in the control group received weekly visits with a nurse for 12 weeks. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013221 •
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 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
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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 •
Innovative Strategies for Implementing New CHF Guideline Recommendations Condition(s): Heart Failure, Congestive Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs Purpose - Excerpt: Clinical practice guidelines are an important avenue for improving health care quality and outcomes, but adherence is often suboptimal. CHF guidelines have recently been revised to incorporate the widespread use of beta-blockers, thus providing a unique opportunity to evaluate strategies for implementing this new recommendation. The initial objective of this proposal is to determine the best strategy to implement beta-blocker therapy in appropriate CHF patients. The long-term objective will be to validate the most effective strategy in a diverse group of VA facilities. In the initial phase, the usual approach, intensive provider education and guideline promotion (the Control group), is being compared to a Provider notification/Patient empowerment strategy that utilizes timely computerized reminders and involves the patient in this aspect of their care, and Nurse Case Management that utilizes a specially trained and supervised nurse practitioner to initiate and titrate beta-blocker therapy. Prevalent CHF patients who were appropriate candidates for beta-blockers were identified and assigned to one of the strategies based on a randomization of their primary provider. The most successful strategy will be determined by the proportion of appropriate patients initiated and maintained on beta-blockers as the primary outcome measure. Secondary outcomes include the proportion achieving target doses, the number of patients deteriorating during initiation, and provider and patient satisfaction with these interventions. In the Implementation/Validation Phase, the most successful strategy in a Level 3 hospital (San Francisco) will be applied to a Level 2 facility (Reno VAMC) and 2 large outpatient clinics of the NCHCS (Martinez and Sacramento/Mather), with the goal of initiating at least 70 percent of appropriate CHF patients on beta-blockers. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012974
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Natural History of Coronary Heart Disease Condition(s): Cardiovascular Diseases; Coronary Disease; Myocardial Infarction; Heart Diseases; Death, Sudden, Cardiac; Heart Failure, Congestive; Heart Failure Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the natural history of mortality due to coronary heart disease in post-myocardial infarction patients from the Beta-Blocker Heart Attack Trial (BHAT) and the Aspirin Myocardial Infarction Study (AMIS). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005265
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Prevention of Early Readmission in Elderly Congestive Heart Failure Patients Condition(s): Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive; Heart Failure Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To assess the impact of a multidisciplinary treatment program on three-month readmission-free survival in elderly congestive heart failure patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000475
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Safety study of Vasopressin V2 Receptor Antagonist on Patients With Severe Chronic Heart Failure (AQUAVIT). Condition(s): Chronic Heart Failure Study Status: This study is completed. Sponsor(s): Sanofi-Synthelabo Purpose - Excerpt: This is a randomized, double-blind, placebo-controlled, parallelgroup forced up-titration study. Randomization will be stratified according to the patient's baseline serum sodium concentration (137-144 and <137 mmol/L). The dose of study drug will be increased to the next level on Day 15, and the total duration of the double-blind treatment period is 120 days. Phase(s): Phase II; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032747
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Study to Compare the Effects of Two Dosages of Tolvaptan in Congestive Heart Failure Patients Condition(s): Congestive Heart Failure
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Study Status: This study is completed. Sponsor(s): Otsuka Maryland Research Institute Purpose - Excerpt: Patients with congestive heart failure will be assessed for safety and clinical effects of Tolvaptan 30 mg every day versus 15 mg twice a day over a period of 7 days. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043771 •
The Role of Angiotensin Type I Receptor in the Regulation of Human Coronary Vascular Function Condition(s): Atherosclerosis; Heart Failure, Congestive; Hypertension; Myocardial Infarction Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The renin angiotensin system (RAS) plays an important physiological and pathophysiological role in the control of blood pressure and plasma volume. Inhibition of the RAS is useful in the treatment of hypertension, cardiac failure and in some patients with myocardial infarction. Several recent clinical trials with angiotensin converting enzyme inhibitors (ACEI) have shown that they also reduce the incidence of myocardial infarction, but the mechanisms underlying this anti-ischemic effect are poorly understood. ACEI reduce angiotensin II synthesis and prevent bradykinin degradation. Results from ongoing studies in the Cardiology Branch (Protocol 95-H0099) designed to investigate the link between ACEI and the vascular endothelium indicate that ACEI improve both endothelial dysfunction and metabolic coronary vasodilation, an effect that is partially mediated by bradykinin. The current protocol is designed to investigate whether the beneficial effects of ACEI on endothelial function are also partly due to inhibition of angiotensin II. The recent development of selective angiotensin II type 1 (AT1) receptor antagonists allows us to specifically examine the effects of angiotensin II on vasomotor activity. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001629
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The Role of Angiotensin Type I Receptor in the Regulation of Human Peripheral Vascular Function Condition(s): Atherosclerosis; Heart Failure, Congestive; Hypertension; Myocardial Infarction Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The renin angiotensin system (RAS) plays an important physiological and pathophysiological role in the control of blood pressure and plasma volume. Inhibition of the RAS is useful in the treatment of hypertension, cardiac failure and in
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some patients with myocardial infarction. Several recent clinical trials with angiotensin converting enzyme inhibitors (ACEI) have shown that they also reduce the incidence of myocardial infarction, but the mechanisms underlying this anti-ischemic effect are poorly understood. ACEI reduce angiotensin II synthesis and prevent bradykinin degradation. Results from ongoing studies in the Cardiology Branch (Protocol 95-H0099) designed to investigate the link between ACEI and the vascular endothelium indicate that ACEI improve peripheral endothelial function, an effect that is partially mediated by bradykinin. The current protocol is designed to investigate whether the beneficial effects of ACEI on peripheral endothelial function are also due to inhibition of angiotensin II. The recent development of selective angiotensin II type 1 (AT1) receptor antagonists allows us to specifically examine the effects of angiotensin II on vasomotor activity. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001628 •
Trial of a Tailored Message Program to Implement CHF Guidelines Condition(s): Congestive Heart Failure Study Status: This study is not yet open for patient recruitment. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service; Indiana University School of Nursing Purpose - Excerpt: We propose a randomized controlled trial to evaluate the effects of an interactive computerized, tailored message intervention to improve patient compliance with evidence-based heart failure guidelines. The long-term goal is to develop a "package" of care to be used directly by veterans with congestive heart failure (CHF). Patients with CHF consume a significant proportion of health care resources, with exacerbation of CHF being the second most common reason for medical admission to VA Medical Centers. Our main objective is to understand the impact of the web as a tool for direct use by patients with CHF on medical resources. Despite the demonstration of reduced mortality by several classes of medications, patients with CHF often do not receive appropriate therapy, and even if they do, many are non-compliant with the treatment regimen. Thus, our second objective: to understand the tool's impact on patient compliance, and a third objective, its impact on quality of life. To accomplish these objectives, we base our study upon Heart Messages; a tailored message educational program designed to improve patient compliance with CHF treatment guidelines. Our plan is to randomize patients to an intervention group, which will use the computerized version of Heart Messages, or a control group, which will receive only standard care as prescribed by their physician (231 patients in each group). Heart Messages assesses patient's beliefs about compliance with medications, diet and selfmonitoring. Based on identified barriers to compliance, intervention patients will receive a tailored educational message to dispel these barriers and improve compliance with prescribed treatment and quality of life over a twelve-month follow-up period. Analyses includes testing three hypotheses: (1) unplanned hospital readmission will be lower in intervention patients; (2) patient compliance with evidence-based CHF treatment guidelines will increase in intervention patients; and (3) quality of life will improve in patients who are compliant with and receiving CHF therapy with
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appropriate statistical tools, including multivariable modeling and repeated measures, regression. Only veterans will be studied. Women and minorities will be represented. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00013026
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 “heart failure” (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/
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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 HEART FAILURE 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.6 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 “heart failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on heart failure, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Heart Failure By performing a patent search focusing on heart failure, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 6Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on heart failure: •
Assessing heart failure status using morphology of a signal representative of arterial pulse pressure Inventor(s): Turcott; Robert (Mountain View, CA) Assignee(s): Pacesetter, Inc. (Sunnyvale, CA) Patent Number: 6,561,984 Date filed: October 16, 2001 Abstract: The heart failure (HF) status of a patient is determined based on the frequency characteristics of a signal representative of arterial pulse pressure. The signal can be a plethysmography signal that is produced by a implantable sensor or a non-implanted sensor. The signal can be produced by a chronically implantable sensor. Excerpt(s): The present invention relates generally to non-invasive and implantable (i.e., invasive) methods, devices and system for assessing heart failure status using morphology of a signal representative of arterial pulse pressure. Specific embodiments of the present invention relate to assessing heart failure status based on the morphology of a plethysmography signal. Heart failure (HF) is a pathophysiologic state in which an abnormality of myocardial function inhibits the ventricles from delivering adequate quantities of blood to metabolizing tissues at rest or during activity. It results not only from a decrease in intrinsic systolic contractility and/or diastolic relaxation of the myocardium but also from alterations in the pulmonary and peripheral circulations as well. HF can develop from a variety of different causes. Coronary artery disease, hypertension, and idiopathic cardiomyopathy are common risk factors for HF. Acute conditions that may result in HF include acute myocardial infarction (AMI), arrhythmias, pulmonary embolism, sepsis, and acute myocardial ischemia. Gradual development of HF may be caused by liver or renal disease, primary cardiomyopathy, cardiac valve disease, anemia, bacterial endocarditis, viral myocarditis, thyrotoxicosis, chemotherapy, excessive dietary sodium intake, and ethanol abuse. Drugs can also worsen HF. Drugs that may cause fluid retention, such as nonsteroidal antiinflammatory drugs (NSAIDs), steroids, hormones, antihypertensives (e.g., hydralazine, nifedipine), sodium-containing drugs (e.g., carbenicillin disodium), and lithium may cause congestion. Beta blockers, antiarrhythmics (e.g., disopyramide, flecainide, amiodarone, sotalol), tricyclic antidepressants, and certain calcium channel blockers (e.g., diltiazem, nifedipine, verapamil) have negative inotropic effects and further decrease contractility in an already depressed heart. Direct cardiac toxins (e.g., amphetamines, cocaine, daunomycin, doxorubicin, ethanol) also can worsen or induce HF. When the heart fails as a pump and cardiac output (the volume of blood pumped out of the ventricle per unit of time) decreases, a complex scheme of compensatory mechanisms to raise and maintain perfusion to vital organs. These compensatory mechanisms include increased preload (volume and pressure or myocardial fiber length of the ventricle prior to contraction, i.e., end of diastole), increased afterload (vascular resistance), ventricular hypertrophy (increased muscle mass) and dilatation, activation of the sympathetic nervous system (SNS), and activation of the renin-angiotensinaldosterone (RAA) system. Web site: http://www.delphion.com/details?pn=US06561984__
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Compounds and methods to treat cardiac failure and other disorders Inventor(s): Lewicki; John A. (Los Gatos, CA), Liu; David Y. (Palo Alto, CA), Mavunkel; Babu J. (Sunnyvale, CA), Perumattam; John J. (Los Altos, CA), Schreiner; George F. (Los Altos Hills, CA) Assignee(s): Scios, Inc. (Sunnyvale, CA) Patent Number: 6,589,954 Date filed: May 21, 1999 Abstract: Indoles, benzimidazoles and benztriazoles which are substituted at the 5 or 6 position with a substituent comprising an aromatic moiety linked through a piperazine ring to said indole, benzimidazole or benztriazole are useful in treating cardiac conditions associated with heart failure and in treating conditions characterized by proinflammation. Excerpt(s): The invention is directed to compounds that are useful in treating inflammation and that contain piperazine or piperidine moieties coupled to the 5- or 6position of indole, benzimidazole or benzotriazole. More particularly, the invention concerns novel ortho substituted indoles and N-substituted indoles as well as methods to treat heart and kidney conditions using these compounds and derivatives thereof. A large number of chronic and acute conditions have been recognized to be associated with perturbation of the inflammatory response. A large number of cytokines participate in this response, including IL-1, IL-6, IL-8 and TNF. It appears that the activity of these cytokines in the regulation of inflammation rely at least in part on the activation of an enzyme on the cell signaling pathway, a member of the MAP kinase family generally known as p38 and alternatively known as CSBP and RK. This kinase is activated by dual phosphorylation after stimulation by physiochemical stress, treatment with lipopolysaccharides or with proinflammatory cytokines such as IL-1 and TNF. Therefore, inhibitors of the kinase activity of p38 are useful antiinflammatory agents. The above-referenced PCT applications disclose compounds which are p38 kinase inhibitors said to be useful in treating these disease states. These compounds are either imidazoles or are indoles substituted at the 3- or 4-position with a piperazine or piperidine ring linked through a carboxamide linkage. Additional compounds which are conjugates of piperazines with indoles are described as insecticides in WO97/26252, also incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06589954__
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Cytoprotective benzofuran derivatives Inventor(s): Chen; Jian (Sunnyvale, CA), Wang; Bing (Cupertino, CA) Assignee(s): Galileo Pharmaceuticals, Inc. (Santa Clara, CA) Patent Number: 6,653,346 Date filed: February 6, 2003 Abstract: Cytoprotective compounds, many of which are benzofuran derivatives are useful in the treatment of certain ischemic or inflammatory conditions, including but not limited to stroke, myocardial infarction, congestive heart failure, and skin disorders characterized by inflammation or oxidative damage. They are also useful in the manufacture of pharmaceutical and cosmetic formulations for the treatment of such conditions.
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Excerpt(s): The present invention relates to certain compounds having cytoprotective activity, and particularly to a series of benzofuran derivatives. The invention is also directed to formulations and methods for treating stroke, myocardial infarction and chronic heart failure, as well as other oxidative stress-related conditions that are typically responsive to cellular enzyme modulation. The invention is also directed to a method of treating inflammation by reducing C-reactive protein (CRP). The invention is also directed to cosmetic formulations for the treatment of skin inflammation and other skin disorders. The present invention is concerned with cytoprotective compounds, which are benzofuran derivatives, said derivatives including steroisomers, mixtures of stereoisomers and therapeutically acceptable salts therof. Compositions of the invention are active in certain experimental models that predict efficacy in, for example, certain ischemic or inflammatory conditions, including but not limited to stroke, myocardial infarction, congestive heart failure, and skin disorders characterized by inflammation or oxidative damage. The invention is therefore related to the use of the cytoprotective derivatives in such conditions. Web site: http://www.delphion.com/details?pn=US06653346__ •
Eprosartan arginyl charge-neutralization-complex and a process for its preparation and formulation Inventor(s): Gudipati; Manga R (Yardley, PA), Jushchyshyn; John M (Lansdowne, PA), Palepu; Nageswara R (Millcreek, WA), Venkatesh; Gopadi M (Blue Brook, OH) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,630,498 Date filed: December 12, 2001 Abstract: This invention relates to (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid arginyl charge-neutralizationcomplex, a process for its production, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to a pharmaceutically active compound, a process for its production, compositions containing the compound and methods of using the compound in the treatment of certain disease states in mammals, in particular man. More specifically, the present invention relates to a charge-neutralization-complex of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2thiophenepropionic acid or its salt form, particularly, the methanesulfonate salt, and Larginine. Most particularly, this invention relates to a 1:1 to a 1:3 molar chargeneutralization-complex of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1Himidazol-5-yl]methyl ene-2-thiophenepropionic acid or its monomethanesulfonate salt and L-arginine (herein referred to as (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid arginyl charge-neutralizationcomplex or eprosartan arginyl charge-neutralization-complex), a wet granulation process for preparing said charge-neutralization-complex, compositions containing this charge-neutralization-complex, and methods of using (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid arginyl charge-neutralization-complex to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound (E)-.alpha.-[2-nbutyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid is known by the name eprosartan and its methanesulfate salt is known as
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eprosartan mesylate. Eprosartan and eprosartan mesylate are the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses in Example 41 a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate. Additionally, the '351 patent discloses conventional techniques for formulating (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate and Examples 108-111 specifically detail the preparation of certain formulations. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. Human clinical studies indicate (E)-.alpha.-[2-n-butyl-1-[(4-carboxy phenyl)methyl]-1H-imidazol-5-yl]methylene-2thiophenepropionic acid monomethanesulfonate to be safe and well tolerated even up to doses of 800 mg per day. The time to maximum concentration is between 1 to 2.5 hours in fasted state and 2.5-4 hours in fed state. (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate exhibits a mean absolute bioavailability of approximately 13%. Web site: http://www.delphion.com/details?pn=US06630498__ •
Expandable cardiac harness for treating congestive heart failure Inventor(s): Hartigan; Bill (Fremont, CA), Lau; Lilip (Sunnyvale, CA) Assignee(s): Paracor Surgical, Inc. (Sunnyvale, CA) Patent Number: 6,595,912 Date filed: September 14, 2001 Abstract: A cardiac harness for treating congestive heart failure is disclosed. The harness applies elastic, compressive reinforcement on the left ventricle to reduce deleterious wall tension and to resist shape change of the ventricle during the mechanical cardiac cycle. Rather than imposing a dimension beyond which the heart cannot expand, the harness provides no hard limit over the range of diastolic expansion of the ventricle. Instead, the harness follows the contour of the heart throughout diastole and continuously exerts gentle resistance to stretch. Also disclosed is a method of delivering the cardiac harness to the heart minimally invasively. Excerpt(s): The present invention relates to mechanical systems for treating congestive heart failure. Specifically, the invention relates to devices that interface mechanically with a patient's failing heart in order to improve its pumping function. Congestive heart failure ("CHF") is characterized by the failure of the heart to pump blood at sufficient flow rates to meet the metabolic demand of tissues, especially the demand for oxygen. Historically, congestive heart failure has been managed with a variety of drugs. There is also a considerable history of the use of devices to improve cardiac output. For example, physicians have employed many designs for powered left-ventricular assist pumps. Multi-chamber pacing has been employed to optimally synchronize the beating of the heart chambers to improve cardiac output. Various skeletal muscles have been investigated as potential autologous power sources for ventricular assist. Among these, dynamic cardiomyoplasty using the latissimus dorsi muscle has attracted the most interest. It has been suggested that the beneficial effects of this procedure stem from both an active, dynamic, systolic assistance and a passive, adynamic girdling of the heart that limits diastolic stretch of the ventricle. To exploit these beneficial clinical features, researchers and cardiac surgeons have experimented with prosthetic "girdles" around the heart. One such design reported in the literature is a prosthetic "sock" that is
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wrapped around the heart. Others have proposed the application of an intraventricular splint to reduce the volume of the left ventricle. Several design shortcomings are apparent with each. Web site: http://www.delphion.com/details?pn=US06595912__ •
Heart failure monitor quicklook summary for patient management systems Inventor(s): Bennett; Tom Dean (Shoreview, MN), Webb; James D. (Maple Grove, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,599,250 Date filed: March 16, 2001 Abstract: Continuous remote monitoring of patients based on data obtained from an implantable hemodynamic monitor provides an interactive patient management system. Using network systems, patients are remotely monitored to continuously diagnose and treat heart-failure conditions. A screen displayable summary provides continuous feedback and information to physicians, patients and authorized third parties. The quick look summary includes various sites and presentation tailored to match the patients' and physicians' needs. The quick look summary further includes intelligent features that understand and retain the user's interests, preferences and use patterns. Patients, physicians and other caregivers are seamlessly connected to monitor and serve the chronic needs of heart-failure patients in a reliable and economic manner. Excerpt(s): The present invention relates to implantable hemodynamic monitors (IHMs). Specifically, the invention relates to systems that interface with various hospital monitoring systems to transfer data from the IHMs to doctors and other data processing centers. More specifically, the invention pertains to heart failure data management systems that provide a concise and reliable summary view of information in a manner that is useful for clinicians and health care personnel to monitor, assess, evaluate and treat heart failure conditions in patients. Further, the invention pertains to a system of a bi-directional communication system that is network, Internet, intranet and worldwide web compatible to enable chronic monitoring based on data obtained from the IHMs. The need to monitor, on a frequent and continuous basis, the vital signs associated with hospitalized patients particularly those who are seriously ill is an important aspect of health care. Virtually every hospitalized patient requires periodic measurement in logging of blood pressure, temperature, pulse rate, etc. Such monitoring has typically been performed by having a health care worker periodically visit the bedside of the patient and measuring and/or observing the patient's vital signs using dedicated equipment that is either hooked up to the patient or brought into the patient's room. Such a monitoring procedure is not ideally cost-effective because of its being highly labor intensive. A great many implantable medical devices (IMDs) for cardiac monitoring and/or therapy whose sensors are located in a blood vessel or heart chamber and coupled to an implantable monitor or therapy delivery device are used for diagnosis and therapy. Such systems include, for example, implantable heart monitors, therapy delivery devices, and drug delivery devices. All these systems include electrodes for sensing and sense amplifiers for recording and/or deriving sense event signals from the intracardiac electrogram (EGM). In current cardiac IMDs that provide a therapy, sensed event signals are used to control the delivery of the therapy in accordance with an operating algorithm. Selected EGM signal segments and sensed event histogram data or the like are stored in an internal RAM for telemetry to be transmitted to an external programmer at a later time. Efforts have also been underway
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for many years to develop implantable physiologic signal transducers and sensors for temporary or chronic use in a body organ or vessel usable with such IHMs for monitoring a physiologic condition other than, or in addition to, the disease state that is to be controlled by a therapy delivered by the IMD. Web site: http://www.delphion.com/details?pn=US06599250__ •
High drug load immediate and modified release oral dosage formulations and processes for their manufacture Inventor(s): Venkatesh; Gopadi M. (Blue Brook, OH) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,558,699 Date filed: December 12, 2001 Abstract: This invention relates to high drug load granulation of (E)-.alpha.-[2-n-butyl-1[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid in the anhydrous form, a process for its production, compositions containing the compound and methods of using the compound to block angiotensin II receptors and to treat hypertension, congestive heart failure and renal failure. Excerpt(s): This invention relates to high drug load formulations, processes for preparing these formulations, and methods of using high drug load formulations in the treatment of certain disease states in mammals, in particular man. Specifically, the present invention relates to the use of anhydrous (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid in the preparation of high drug load immediate and modified release tablet formulations, wet or dry granulation processes for preparing high drug load granules, oral dosage forms containing these high drug load granules, and methods of using high drug load formulations of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5yl]methyle ne-2-thiophenepropionic acid to block angiotensin II (AII) receptors and to treat hypertension, congestive heart failure and renal failure. The compound, (E).alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyle ne-2thiophenepropionic acid, is known by the name "eprosartan" and is the subject of U.S. Pat. No. 5,185,351 (the '351 patent), issued Feb. 9, 1993. This patent discloses a process for making the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid and its methane sulfonate salt. Additionally, the '351 patent discloses conventional techniques for formulating (E).alpha.-[2-n-butyl-1-[(4-carboxyphenyl)-methyl]-1H-imidazol-5-yl]methy lene-2thiophenepropionic acid. This compound is claimed to have utility in blocking angiotensin II receptors and to be useful in the treatment of hypertension, congestive heart failure and renal failure. International Application Number PCT/US97/04877, filed Mar. 26, 1997. relates to a novel dihydrated form of (E)-.alpha.-[2-n-butyl-1-[(4carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2-thiophenepropionic acid monomethanesulfonate, in particular, in pharmaceutical compositions for the treatment of diseases in which blockade of angiotensin II receptors is indicated, for example, in the treatment of hypertension, congestive heart failure and renal failure. This form of (E).alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methyl ene-2thiophene-propionic acid monomethanesulfonate is produced during the wet granulation of the anhydrous form of (E)-.alpha.-[2-n-butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl]methy lene-2-thiophenepropionic acid monomethanesulfonate.
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Web site: http://www.delphion.com/details?pn=US06558699__ •
Implantable dual site cardiac stimulation device having independent automatic capture capability Inventor(s): Kroll; Mark W. (Simi Valley, CA) Assignee(s): Pacesetter, Inc. (Sylmar, CA) Patent Number: 6,549,806 Date filed: October 5, 2000 Abstract: An improved device and method for automatically determining threshold detection and maintaining capture in a multiple, e.g., dual, site cardiac stimulation device. When multiple site stimulation is used, e.g., for treatment of congestive heart failure (CHF) or the like, the threshold stimulation energy level at each of the sites will typically be different and, in the case of a lead implanted in the coronary sinus (CS), threshold stimulation energy level may be significantly different, e.g., 50 times greater or more. Accordingly, embodiments of the present invention independently maintain capture for each site and, preferably, independently determine the threshold for each site. In a significant aspect of the present invention, a preferred device periodically determines the chronaxie and rheobase corresponding to a strength-duration curve for each site and sets initial controlled energy levels accordingly. Once each initial controlled energy level is determined, which preferably includes a safety margin, the controlled energy level is increased when a loss-of-capture criteria is met. Furthermore, power expended from the battery is minimized since each site is individually optimized. Excerpt(s): The present invention is generally directed to an implantable medical device, e.g., a cardiac stimulation device, and is particularly directed to an automatic capture/threshold pacing method for use in such a device. Implantable cardiac stimulation devices are well known in the art. They include implantable pacemakers which provide stimulation pulses to cause a heart, which would normally beat too slowly or at an irregular rate, to beat at a controlled normal rate. They also include defibrillators which detect when the atria and/or the ventricles of the heart are in fibrillation or in a pathologic rapid rhythm and then apply cardioverting or defibrillating electrical energy to the heart to restore and maintain the heart in a normal rhythm. Implantable cardiac stimulation devices may also include the combined functions of a pacemaker and a defibrillator. As is well known, implantable cardiac stimulation devices sense cardiac activity for monitoring the cardiac condition of the patient in which the device is implanted. By sensing the cardiac activity of the patient, the device is able to provide cardiac stimulation pulses when they are needed and inhibit the delivery of cardiac stimulation pulses at other times. This inhibition accomplishes two primary functions. Firstly, when the heart is intrinsically stimulated, the patient's hemodynamics are generally improved. Secondly, inhibiting the delivery of a cardiac stimulation pulse reduces the overall battery current drain and therefore extends the life of the device battery. Extending the battery life, will therefore delay the need to explant and replace the cardiac stimulation device due to an expended battery. Generally, the circuitry used in implantable cardiac stimulation devices has been significantly improved since their introduction such that the major limitation of the battery life is related primarily to the number and amplitude of the stimulation pulses. Accordingly, it is preferable to minimize the number of pulses delivered by using this inhibition function and to minimize the amplitude of the pulses when it is clinically appropriate.
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Web site: http://www.delphion.com/details?pn=US06549806__ •
Kits for early detection of heart disease Inventor(s): Sabbadini; Roger A. (Lakeside, CA) Assignee(s): Medlyte Diagnostics, Inc. (San Diego, CA) Patent Number: 6,534,322 Date filed: January 21, 2000 Abstract: The invention relates to methods, compositions, kits, and devices for detecting cardiac ischemia, hypoxia, or other causes of heart failure in a mammal by obtaining a test sample from a mammal, measuring a level of a non-polypeptidic cardiac marker in the test sample, and determining if the level of the cardiac marker measured in said test sample correlates with cardiac ischemia or hypoxia or another form of heart failure. Excerpt(s): This invention relates generally to the area of diagnosis of heart disease, and specifically relates to methods of diagnosis of heart failure, cardiac ischemia, or hypoxia by detecting the level, e.g., concentration, of a non-polypeptidic cardiac marker as an indicator of heart damage, particularly chronic underlying coronary artery disease, and for monitoring of therapeutic regimes designed to alleviate cardiac ischemia or hypoxia. Ischemic heart disease is the major form of heart failure. Heart failure affects millions of people worldwide and is the leading cause of death in the United States. The most common manifestation of cardiac ischemia is chest pain (angina pectoris) which can lead to heart attack (acute myocardial infarction or AMI) and sudden death. In addition to those who exhibit clinical symptoms of ischemic heart disease, many other individuals are at high risk of developing heart disease based on indicators such as hypertension conditions, high levels of serum cholesterol and/or family history. Myocardial ischemic disorders occur when cardiac blood flow is restricted (ischemia) and/or when the oxygen supply to heart muscle is compromised (hypoxia) such that the heart's demand for oxygen is not met. Atherosclerosis of the coronary artery is the most common cause of ischemia-associated symptoms such as angina pectoris. Ischemia and hypoxia can be transient and reversible, but can also lead to infarction. During infarction, cardiac tissue is damaged and the heart cells become permeabilized, releasing a portion of their contents to the surrounding milieu, including cardiac enzymes and other biochemical markers. These cellular markers, such as creatine kinase (CK), lactic acid dehydrogenase (LDH) enzymatic activities and creatine kinase-MB (CKMB) and troponin (I and T) and myoglobin mass levels, are then detectable in the serum. Web site: http://www.delphion.com/details?pn=US06534322__
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Method and apparatus for providing positive airway pressure to a patient Inventor(s): Estes; Mark C. (Harrison City, PA), Fiore; John H. (Monroeville, PA), Machlenburg; Douglas M. (Pittsburgh, PA) Assignee(s): Respironics, Inc. (Murrysville, PA) Patent Number: 6,609,517 Date filed: July 6, 2000 Abstract: A system including methods and apparatus for treatment of a medical disorder such as obstructive sleep apnea or congestive heart failure. The system
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involves applying separate and independent gains to flow rates of pressurized gas delivered to a patient during inspiratory and expiratory phases of a respiratory cycle to deliver the pressurized gas in proportion to the respective gains during inspiration and expiration. A base pressure may be applied in addition to the gain-modified pressures and an elevated pressure profile may be employed to assist or control inspiration. The system may be fully automated responsive to feedback provided by a flow sensor that determines the estimated patient flow rate. A leak computer can be included to instantaneously calculate gas leakage from the system. The system may be utilized in connection with conventional continuous positive airway pressure (bi-level PAP) equipment to effect various beneficial treatment applications. Excerpt(s): The present invention relates generally to methods and apparatus for treating breathing and/or cardiac disorders and, more particularly, to methods and apparatus for providing a pressure to an airway of a patient during at least a portion of the breathing cycle to treat obstructive sleep apnea syndrome, chronic obstructive pulmonary disease, congestive heart failure, and other respiratory and/or breathing disorders. During obstructive sleep apnea syndrome (OSAS), the airway is prone to narrowing and/or collapse while the patient sleeps. Continuous positive airway pressure (CPAP) therapy seeks to avoid this narrowing by supplying pressure to splint the airway open. With CPAP, this splinting pressure is constant and is optimized during a sleep study to be sufficient in magnitude to prevent narrowing of the airway. Providing a constant splinting pressure, i.e., CPAP, is a simple solution to the problem posed by the collapsing airway. However, this approach exposes the patient to pressures that are higher than the pressures needed to support the airway for most of the breathing cycle. During inspiration, the pressure created within the lungs is lower than the pressure at the nose. This pressure difference drives the flow of air into the lungs. This pressure difference creates a pressure gradient in the airway connecting the lungs with the nose. That is to say, the nose is typically at ambient pressure while the lungs and airway of the patient are at sub-ambient or negative pressures. This negative pressure acts upon the airway and contributes to its collapse. CPAP levels are typically set to raise the pressure level in the entire respiratory system to the level required to both eliminate the sub-ambient pressures generated by inspiration and overcome any mechanical collapsing forces that result from the structure of the airway tissues, muscle tone, and body position. The inspiratory pressures , i.e., inspiratory positive airway pressure or "IPAP," in bi-level positive airway pressure systems are set in a similar manner. Web site: http://www.delphion.com/details?pn=US06609517__ •
Method and devices for decreasing elevated pulmonary venous pressure Inventor(s): Shaknovich; Alexander (New York, NY) Assignee(s): VenPro Corporation (Irvine, CA) Patent Number: 6,572,652 Date filed: March 20, 2001 Abstract: The present invention relates to the implantation of one or more prosthetic valve(s) in the pulmonary vein(s) of a subject for decreasing or preventing an increase in pulmonary venous pressure. The present invention accordingly provides for novel treatment strategies for the treatment of medical disorders associated with elevated pulmonary venous pressure, including congestive heart failure, as well as for prosthetic pulmonary vein valves and their delivery systems. Expandable as well as fixed-
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dimension non-expandable pulmonary vein prosthetic valves for implantation by a variety of surgical and percutaneous procedures are also described. Excerpt(s): The present invention relates to the implantation of one or more prosthetic valve(s) in the pulmonary vein(s) of a subject as a means of decreasing or preventing an increase in pulmonary venous pressure. The present invention accordingly provides novel strategies for the treatment of medical disorders associated with elevated pulmonary venous pressure, including congestive heart failure, as well as for prosthetic pulmonary vein valves and their delivery systems. Expandable as well as fixeddimension non-expandable pulmonary vein prosthetic valves for implantation by a variety of surgical and percutaneous procedures are also described. Certain larger veins in the lower extremities of human beings normally have valves that, under conditions of normal function, permit movement of blood largely only toward the heart. In effect, properly functioning venous valves in the lower extremities protect, or partition, the veins of the lower extremities from the relatively high hydrostatic pressure of the column of venous blood between the right atrium and the lower extremities due to the effect of gravity during upright posture. Thus, normally, when upright posture is assumed, venous blood pressure in the foot is generally less than the sum of relatively low pressure in the right atrium and relatively high hydrostatic pressure of the column of venous blood between the right atrium and the foot due to the effect of gravity. When these venous valves in the lower extremities are incompetent, venous blood pressure in the foot becomes predominantly equal to the sum of the relatively low pressure in the right atrium and relatively high hydrostatic pressure of the column of venous blood between the right atrium and the foot, often resulting in pathologic dilatation of the veins in the lower extremities and/or edema. A prosthetic valve is an endoprosthesis typically formed of biological, synthetic or composite material, the final deployed diameter of which is suitable for implantation in the intended location in the heart or vascular conduits, such as arteries or veins. A prosthetic valve, when implanted and operating as intended, predictably directs the flow of blood through it. For example, a prosthetic aortic valve allows expulsion of blood from the left ventricle into the aorta during systole, and prevents reflux of blood into the left ventricle from the aorta during diastole. When used for replacement or repair of diseased native cardiac or vascular valves, prosthetic valves may relieve inappropriate obstruction to normally directed blood flow by narrowed or stenotic valves, or may restore appropriate hindrance to abnormally directed blood flow caused by leaking or regurgitant valves. Prosthetic valves are usually implanted by means of open surgical procedures, under general anesthesia and often with ventilatory and circulatory support, in which a surgeon exposes a diseased target valve to be replaced, resects and removes it, and implants an appropriate prosthetic valve in its place. Various types and designs of prosthetic valves for diverse clinical applications related to damage to and/or inappropriate function of the native cardiac valves have been described since the original report by Hufnagel et al., 1954, Surgery 35:573. A number of United States Patents have been issued relating to methods for percutaneous delivery of prosthetic valves and associated delivery methods, including, but not limited to, U.S. Pat. No. 5,332,402 by Teitelbaum, U.S. Pat. No. 5,397,351 by Pavenik et al., U.S. Pat. No. 5,607,465 by Camilli, U.S. Pat. No. 5,855,601 by Bessler et al., U.S. Pat. No. 5,163,953 by Vince, and U.S. Pat. No. 5,411,552 by Andersen et al. Web site: http://www.delphion.com/details?pn=US06572652__
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Method and system for monitoring heart failure using rate change dynamics Inventor(s): Begemann; Malcolm J. (CG Velp, NL) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,636,762 Date filed: April 30, 2001 Abstract: A method of monitoring heart failure is provided. A baseline heart rate change value is determined, wherein the baseline heart rate change value comprises a speed at which a first initial heart rate changes to a second initial heart rate. At least one subsequent heart rate change value is also determined, wherein the subsequent heart rate change value comprises a subsequent speed at which a first subsequent heart rate changes to a second subsequent heart rate. The subsequent heart rate change value is compared to the baseline heart rate change value to obtain at least one heart failure value. Systems and programs for using the method are also provided. Excerpt(s): The present invention relates to the field of medical monitoring devices. More particularly, the present invention relates to cardiac pacing systems that provide a method for monitoring heart failure based on the speed of rate changes in the hemodynamic performance of the heart. Heart failure is a disease that may be characterized by such symptoms as left ventricular dysfunction, arrhythmias, pulmonary and peripheral congestion, fatigue and shortness of breath. In earlier stages, patients may not be able to perform strenuous activities and, in later stages, may not even be able to perform routine activities such as climbing the stairs. Furthermore, the relationship between inability to perform strenuous activities and the corresponding state of the patient's heart may be difficult to discern and quantify. Close monitoring of patients who experience heart failure or who are determined to be at risk for heart failure may be desirable. However, such monitoring presents some difficulties. For example, each patient's heart differs from that of another patient. One patient in earlier stages of heart failure may have a different activity profile than another, more physically fit patient, in the same stage of heart failure. Additionally, external methods of monitoring heart failure in a patient may be awkward. For example, a patient may seem to be in one stage of heart failure while being assessed at his physician's office while in fact, his actual everyday activities would indicate he is in a completely different stage of heart failure. Moreover, invasive methods of more closely examining a patient's stage of heart failure may not be desirable in all patients, such as those who are in reasonably early stages. Web site: http://www.delphion.com/details?pn=US06636762__
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Method for monitoring heart failure via respiratory patterns Inventor(s): Fishler; Matthew G. (Sunnyvale, CA), Street; Anne M. (Sunnyvale, CA) Assignee(s): Pacesetter, Inc. (Sunnyvale, CA) Patent Number: 6,589,188 Date filed: May 5, 2000 Abstract: Detection and monitoring of periodic breathing (PB) to provide an indication of changes in the hemodynamic status of a heart failure patient is accomplished by monitoring at least one of four independent physiologic parameters. The physiologic parameters are respiratory tidal volume, respiratory rate (B-B interval), arterial oxygen
Patents 187
saturation (SaO.sub.2) and heart rate (R-R interval). The data collected of these physiologic measures may then be analyzed by performing power spectral analysis or thresholding/binning. Each analysis method can be applied to each measure or combination thereof. In the preferred embodiment, the physiologic measures are made when the patient has been identified as being at rest or asleep to prevent interference from activity-related respiratory variations. Excerpt(s): This invention relates generally to implantable monitoring devices and implantable cardiac therapy devices, and more particularly to a method for monitoring the respiratory patterns of a chronic heart failure patient to track changes in disease state. Congestive heart failure (CHF) is a debilitating, end-stage disease in which abnormal function of the heart leads to inadequate blood flow to fulfill the needs of the body's tissues. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately fill with blood between heartbeats and the valves regulating blood flow may become leaky, allowing regurgitation or backflow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness, and inability to carry out daily tasks may result. Not all CHF patients suffer debilitating symptoms immediately. Some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive. Web site: http://www.delphion.com/details?pn=US06589188__ •
Method for monitoring heart failure via respiratory patterns Inventor(s): Turcott; Robert (Menlo Park, CA) Assignee(s): Pacesetter, Inc. (Sunnyvale, CA) Patent Number: 6,600,949 Date filed: May 5, 2000 Abstract: A method for monitoring the condition of a heart failure patient using respiration patterns is provided. An implantable or other ambulatory monitor senses the patient's respiratory patterns to identify the presence of periodic breathing or CheyneStokes respiration. In a first embodiment, mechanical changes of the thorax due to breathing are detected and this data is used to recognize hyperventilation and apnea or hypoventilation. In a second embodiment of the invention, Cheyne-Stokes respiration is recognized by detecting changes in blood or tissue pH or CO.sub.2 concentration and partial pressure. In another embodiment of the invention, changes in pulse amplitude associated with Cheyne-Stokes respiration are detected. Alternating loss and return of respiration-induced amplitude modulation or pulse-interval variation may also be used to identify the presence of Cheyne-Stokes respiration. In yet another embodiment of the invention, modulation of the average heart rate over time is monitored and its absence is used as an indicator of Cheyne-Stokes respiration. This information may be used to warn the patient or healthcare provider of changes in the patient's condition warranting attention. Excerpt(s): This invention relates generally to implantable monitoring devices, and more particularly to a method for monitoring the hemodynamic status of a patient with a chronic disease such as heart failure, ischemic heart disease, or diabetes. Many chronic diseases, such as diabetes and heart failure, require close medical management to reduce morbidity and mortality. Because the disease status evolves with time, frequent physician follow-up examinations are often necessary. At follow-up, the physician may
188 Heart Failure
make adjustments to the drug regimen in order to optimize therapy. This conventional approach of periodic follow-up is unsatisfactory for some diseases, such as heart failure, in which acute, life-threatening exacerbations can develop between physician follow-up examinations. It is well know among clinicians that if a developing exacerbation is recognized early, it can be easily and inexpensively terminated, typically with a modest increase in oral diuretic. However, if it develops beyond the initial phase, an acute heart failure exacerbation becomes difficult to control and terminate. Hospitalization in an intensive care unit is often required. It is during an acute exacerbation of heart failure that many patients succumb to the disease. It is often difficult for patients to subjectively recognize a developing exacerbation, despite the presence of numerous physical signs that would allow a physician to readily detect it. This problem is well illustrated by G. Guyatt in his article entitled "A 75-Year-Old Man with Congestive Heart Failure," 1999, JAMA 281(24)2321-2328. Furthermore, since exacerbations typically develop over hours to days, even frequently scheduled routine follow-up with a physician cannot effectively detect most developing exacerbations. It is therefore desirable to have a system that allows the routine, frequent monitoring of patients so that an exacerbation can be recognized early in its course. With the patient and/or physician thus notified by the monitoring system of the need for medical intervention, a developing exacerbation can easily and inexpensively be terminated early in its course. The multiplicity of feedback mechanisms that influence cardiac performance places the heart at the center of a complex control network. The neurohumoral axis includes the autonomic nervous system, consisting of sympathetic and parasympathetic branches, and numerous circulating hormones such as catacholamines, angiotensin, and aldosterone. Neural reflex arcs originating from pressure and stretch receptors, which directly measure mechanical hemodynamic status, modulate the neurohumoral axis. Similarly, chemoreceptors respond to changes in CO2, pH, and O2, which assesses cardiopulmonary function. The neurohumoral system influences cardiac performance at the level of the cardiac electrical system by regulating heart rate and the conduction velocity of electrical depolarizations. It also influences cardiac performance at the mechanical level, by controlling contractility, that is, the effective vigor with which the heart muscle contracts. Conventional cardiac monitors, such as defibrillators, pacemakers, Holter monitors, and cardiac event records, are tailored for the diagnosis and/or therapy of abnormalities of the cardiac electrical system. In contrast, heart failure is a disease of the cardiac mechanical system: it is primarily a failure of the myocardium to meet the mechanical pumping demands required of it. In monitoring the status of a heart failure patient, measuring the mechanical hemodynamic variables is clearly desirable. Examples of mechanical hemodynarnic variables include atrial, ventricular, and arterial pressures, and cardiac output (volume of blood pumped into the aorta per unit time). However, because of the complex feedback network that monitors and controls cardiac performance, measuring variables that do not directly reflect the mechanical performance of the heart is also useful. In this way, measuring cardiac electrical activity to assess heart rate variability (described below) allows one to infer the state of the autonomic nervous system, which allows one to infer information about the hemodynamic status of a heart failure patient. Similarly, recognition of Cheyne-Stokes respiration (described below) via respiratory pattern analysis, hemoglobin saturation analysis, and blood gas analysis allows one to detect the presence of pulmonary edema, and thereby detect an acute heart failure exacerbation, though none of these parameters directly measure mechanical hemodynamic status. Web site: http://www.delphion.com/details?pn=US06600949__
Patents 189
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Method for monitoring patient using acoustic sensor Inventor(s): Turcott; Robert (Mountain View, CA) Assignee(s): Pacesetter, Inc. (Sunnyvale, CA) Patent Number: 6,527,729 Date filed: October 11, 2000 Abstract: A method for monitoring the progression of the disease of a heart failure patient is provided. An implantable or other ambulatory monitor senses acoustic signals including heart and lung sounds within the patient. Significant changes in the energy content of either the heart or lung sounds is indicative of a heart failure exacerbation. This information may be used to warn the patient or healthcare providers of changes in the patient's condition warranting attention. Excerpt(s): This invention relates generally to implantable monitoring devices, and more particularly to a method for monitoring the status of a patient- with a chronic disease such as heart failure using heart and lung sounds. Many chronic diseases, such as diabetes and heart failure, require close medical management to reduce morbidity and mortality. Because the disease status evolves with time, frequent physician follow-up examinations are often necessary. At follow-up, the physician may make adjustments to the drug regimen in order to optimize therapy. This conventional approach of periodic follow-up is unsatisfactory for some diseases, such as heart failure, in which acute, lifethreatening exacerbations can develop between physician follow-up examinations. It is well know among clinicians that if a developing exacerbation is recognized early, it can be easily and inexpensively terminated, typically with a modest increase in oral diuretic. However, if it develops beyond the initial phase, an acute heart failure exacerbation becomes difficult to control and terminate. Hospitalization in an intensive care unit is often required. It is during an acute exacerbation of heart failure that many patients succumb to the disease. It is often difficult for patients to subjectively recognize a developing exacerbation, despite the presence of numerous physical signs that would allow a physician to readily detect it. This problem is well illustrated by G. Guyatt in his article entitled "A 75-Year-Old Man with Congestive Heart Failure," 1999, JAMA 281(24)2321-2328. Furthermore, since exacerbations typically develop over hours to days, even frequently scheduled routine follow-up with a physician cannot effectively detect most developing exacerbations. It is therefore desirable to have a,.system that allows the routine, frequent monitoring of patients so that an exacerbation can be recognized early in its course. With the patient and/or physician thus notified by the monitoring system of the need for medical intervention, a developing exacerbation can easily and inexpensively be terminated early in its course. Web site: http://www.delphion.com/details?pn=US06527729__
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Method for the treatment or prevention of coronary graft vasospasm Inventor(s): Lehtonen; Lasse (Espoo, FI), Papp; Julius (Szeged, HU), Szecsi; Janos (Szeged, HU) Assignee(s): Orion Corporation (Espoo, FI) Patent Number: 6,593,329 Date filed: May 30, 2002
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Abstract: Levosimendan, or (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3pyridazinyl)phenyl]hydrazono] -propanedinitrile, which has been previously suggested for the treatment of congestive heart failure is useful in the treatment or prevention of coronary graft vasospasm after coronary artery by-pass surgery. Excerpt(s): This application is a national stage filing of PCT International Application No. PCT/FI00/00592, filed on Jun. 29, 2000, which published in the English language. This application also claims the benefit of priority to patent application no. 9915179.1, filed in Great Britain on Jun. 29, 1999. The present invention relates to a method for the treatment or prevention of coronary graft vasospasm after coronary artery by-pass surgery by administering levosimendan, or (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3pyridazinyl)phenyl]-hydrazono propanedinitrile (I), or pharmaceutically acceptable salts thereof, to a patient in need of such prevention or treatment. The hemodynamic effects of levosimendan in man are described in Sundberg, S. et al., Am. J. Cardiol., 1995; 75: 1061-1066 and in Lilleberg, J. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S63-S69, 1995. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Phannacol., 26(Suppl.1), S57-S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients. Web site: http://www.delphion.com/details?pn=US06593329__ •
Method of inotropic treatment of heart disease using hypothermia Inventor(s): Dae; Michael W. (Belmont, CA), Stull; Paul M. (San Mateo, CA) Assignee(s): Radiant Medical, Inc. (Redwood City, CA) Patent Number: 6,607,517 Date filed: August 24, 2001 Abstract: A method for treating cardiac failure such as congestive heart failure by application of hypothermia. Hypothermia may be applied by endovascular cooling using a heat exchange catheter circulating heat exchange fluid between an external heat exchanger controlled using temperature feedback from a temperature probe on or in the patient to cool the heart to a sufficiently low temperature for a sufficient length of time to increase cardiac output and improve the vascular condition of the patient. The patient may be maintained in the hypothermic condition for a period of time and is then rewarmed slowly and controllably. The endovascular temperature management may be controlled automatically in response to a temperature probe on the patient, and shivering while the patient is cool may be combated using surface warming and antishivering drugs. The method is applicable to treat congestive heart failure and may be used repeatedly on the same patient to restore that patient to adequate heart function when the vascular condition of that patient has become unacceptable. The method may be used to maintain a patient until a heart transplant becomes available. The method may be used to stabilize a patient's condition to allow needed surgery or intervention. The method may be used in conjunction with other treatments including drugs, balloon pumps, pacing devices and ventricular assist devices. Excerpt(s): This invention relates generally to methods for medical treatment and more particularly to the application of hypothermia by various means including by endovascular heat exchange to treat chronic heart disease. These methods find particular usefulness in treating congestive heart failure. The condition of heart failure
Patents 191
is complex and may be diagnosed by any one or a number of different criteria: the cardiac output may be low, generally consideredbelow 2.5 liters per minute; the stroke volume of the heart may be low, for example below 25 cc; the ejection fraction of the sick heart may be below 40%; there may be echocardiographic findings of enlarged or improperly pumping hear; physical examinations including x-rays and stress testing may indicate cardiac failure; there may be cardiomegally; there may be increased left ventricular wall thickness and chamber dilation indicative of cardiac failure; there may be pulmonary edema, which with other sympotoms and findings may indicate cardiac failure; there may be angiographic findings indicative of heart failure; and a diagnostic test of blood components, such as electrolytes or proteins may indicate heart failure. This lis is not exhaustive of the symptoms and findings that may help diagnose heart failure, but is offered to show the extent to which heart failure impacts the entire patient and may radically deteriorate the patient's life quality. One common condition is congestive heart failure (CHF). CHF is one of the most serious health problems in the world. An estimated 4.8 million Americans alone have CHF. It is often the end stage of serious heart disease; half of those diagnosed with CHF will be dead within 5 years. An estimated 400,000 new case are diagnosed each year. It is the most common diagnosis in hospital patients age 65 years and older, with the disease affecting 10% of all those over the age of 70. The financial cost of treatment of CHF patients is over $17 billion a year. The human cost is beyond measure. Web site: http://www.delphion.com/details?pn=US06607517__ •
Method to treat chronic heart failure and/or elevated cholesterol levels using 3,5diiodothyropropionic acid and method to prepare same Inventor(s): Bahl; Joseph J. (Tucson, AZ), Goldman; Steven (Tucson, AZ), Morkin; Eugene (Tucson, AZ), Pennock; Gregory D. (Tucson, AZ) Assignee(s): Southern Arizona Veterans Affairs Health Care System (Tucson, AZ), The Arizona Board of Regents on Behalf of the University of Arizona (Phoenix, AZ) Patent Number: 6,534,676 Date filed: January 31, 2001 Abstract: Applicants' invention includes a method to treat a patient having congestive heartfailure by administering a therapeutically effective amount of 3,5diidothyropropionic acid. Applicants' invention further includes a method to lower cholesterol blood levels of a patient by administering a therapeutically effective amount of 3,5-diidothyropropionic acid. Applicants' invention further includes a synthetic method to prepare 3,5-diidothyropropionic acid. Excerpt(s): The present invention relates to a treatment for patients having congestive heart failure and/or elevated cholesterol blood levels by administering a therapeutically effective amount of 3,5-Diiodothyropropionic acid. The present invention further relates to a synthetic method to prepare 3,5-Diiodothyropropionic acid. Congestive heart failure continues to be a major health problem, affecting about 4.6 million people in the United States, and its prevalence is predicted to increase over the next several decades. The magnitude of heart failure as a clinical problem has placed emphasis on the need to develop new treatment strategies. One approach that has emerged is the use of thyroid hormone, which has unique physiologic and biochemical actions that make it a novel and potentially useful agent for treatment of heart failure. Thyroid hormone has been shown to act at the transcriptional level on the content of myocardial calcium cycling proteins to stimulate calcium uptake by
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sarcoplasmic reticulum. In addition, thyroid hormone causes a reciprocal shift in cardiac myosin heavy chain (MHC) isoform expression, increasing the expression of the high activity V.sub.1 isoform and decreasing the low activity V.sub.3 form. These biochemical alterations may underlie the ability of thyroid hormone to increase the rates of ventricular pressure development and relaxation. Web site: http://www.delphion.com/details?pn=US06534676__ •
Methods for treating congestive heart failure Inventor(s): Kelly; Ralph (Chestnut Hill, MA), Lorell; Beverly (Needham, MA), Marchionni; Mark (Arlington, MA), Sawyer; Douglas B. (Brookline, MA) Assignee(s): CeNes Pharmaceuticals, Inc. (Cambridge) Patent Number: 6,635,249 Date filed: April 23, 1999 Abstract: The invention features methods of treating or preventing congestive heart failure by administering a polypeptide containing an epidermal growth factor-like domain encoded by a neuregulin gene. Excerpt(s): The field of the invention is treatment and prevention of congestive heart failure. Congestive heart failure, one of the leading causes of death in industrialized nations, results from an increased workload on the heart and a progressive decrease in its pumping ability. Initially, the increased workload that results from high blood pressure or loss of contractile tissue induces compensatory cardiomyocyte hypertrophy and thickening of the left ventricular wall, thereby enhancing contractility and maintaining cardiac function. However, over time, the left ventricular chamber dilates, systolic pump function deteriorates, cardiomyocytes undergo apoptotic cell death, and myocardial function progressively deteriorates. Factors that underlie congestive heart failure include high blood pressure, ischemic heart disease, exposure to cardiotoxic compounds such as the anthracycline antibiotics, and genetic defects known to increase the risk of heart failure. Web site: http://www.delphion.com/details?pn=US06635249__
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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) Assignee(s): Quetzal Biomedical, Inc. (Denver, CO) Patent Number: 6,643,546 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
Patents 193
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 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://www.delphion.com/details?pn=US06643546__ •
N-acyl homoserine lactones for the treatment of cardiac tachyarrhythmias, ischaemic heart disease or congestive heart failure Inventor(s): Bennett; Terence (Nottingham, GB), Bycroft; Barrie Walsham (Nottingham, GB), Gardiner; Sheila Margaret (Nottingham, GB), Pritchard; David Idris (Leics, GB), Williams; Paul (Nottingham, GB) Assignee(s): The University of Nottingham (Nottingham, GB) Patent Number: 6,602,905 Date filed: August 21, 2002 Abstract: Compounds having anti-fibrotic effects are provided. Also provided is a method for treating disorders, diseases or conditions associated with pathological fibrotic states. The compounds useful in the present invention are homocysteine thiolactone and selected derivatives thereof. Excerpt(s): This invention relates to certain N-acyl homoserine lactones which have use in the treatment or prevention of cardiac tachyarrhythmias, ischaemic heart disease or congestive heart failure. It, further, relates to a method for the treatment or prevention of tachyarrhythmias, ischaemic heart disease or congestive heart failure and to compositions used in the method. Many anti-arrhythmic agents and compounds for the treatment of ischaemic heart disease or congestive heart failure that are currently used clinically have several unwanted side effects. One such side effect is hypotension. It is a major disadvantage that in slowing down the heart beat, an anti-arrhythmic drug also, for example, reduces the average blood pressure. The present invention is based on the discovery by the inventors that certain N-acyl homoserine lactone compounds can reduce the heart beat without substantially reducing arterial blood pressure. wherein n
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is 2 or 3; Y is O, S or NH; X is O, S or NH; and R.sup.1 is C.sub.1 -C.sub.18 alkyl or acyl which may be substituted have use in the treatment of allergic diseases, such as asthma, hayfever and autoimmune diseases. There is, however, no teaching or suggestion in this document that a defined subgroup of AHL compounds has any activity that could make such compounds useful in the management of tachyarrythmias, ischaemic heart disease or congestive heart failure. Web site: http://www.delphion.com/details?pn=US06602905__ •
Partial fatty acid oxidation inhibitors in the treatment of congestive heart failure Inventor(s): Blackburn; Brent (Los Altos, CA), Sabbah; Hani Naief (Waterford, MI), Stanley; William Clark (Shaker Heights, OH), Wolff; Andrew A. (San Francisco, CA) Assignee(s): CV Therapeutics, Inc. (Palo Alto, CA) Patent Number: 6,528,511 Date filed: February 15, 2001 Abstract: Methods are disclosed for treating congestive heart failure with partial inhibitors of fatty acid oxidation. The compounds increase cardiac performance without affecting heart rate, blood pressure, or oxygen consumption. Excerpt(s): This invention relates to a method of treating congestive heart failure by increasing cardiac performance without increasing myocardial oxygen consumption. In particular, the invention relates to a method of treating congestive heart failure with compounds that partially inhibit fatty acid oxidation. This invention also relates to pharmaceutical formulations that maintain plasma concentrations of such compounds at therapeutically effective levels for extended periods of time. Congestive heart failure (CHF) is a major cause of death and disability in industrialized society. It is not a disease in itself, but a condition in which the heart is unable to pump an adequate supply of blood to meet the oxygen requirements of the body's tissues and organs. As a result, fluid accumulates in the heart and other organs, such as the lungs, and spreads into the surrounding tissues. CHF is often a symptom of cardiovascular problems such as coronary artery disease, myocardial infarction, cardiomyopathy, heart valve abnormalities, and the like. Conventionally, CHF has been treated with a wide variety of drugs, including alpha-adrenergic agonists, beta-adrenergic antagonists, calcium channel antagonists, cardiac glycosides, diuretics, nitrates, phosphodiesterase inhibitors, prazosin, and a variety of vasodilators. All of these drugs, however, have undesirable side-effects. For example, use of alpha-adrenergic agonists results in edema of the peripheral tissues.beta.-adrenergic agents are effective initially, but prolonged use leads to the progressive development of desensitization to the drug. Treatment with cardiac glycosides is well known to produce toxic side-effects in the CNS, and also the gastrointestinal and respiratory systems. Cardiac glycosides additionally produce proarrhythmic effects. Treatment with diuretics may result in a variety of adverse-effects, the most severe of which include electrolyte abnormalities, such as hyponatremia, hypokalemia, and hyperchloremic metabolic alkalosis. Web site: http://www.delphion.com/details?pn=US06528511__
Patents 195
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Preventing desensitization of receptors Inventor(s): Koch; Walter J. (Durham, NC), Lefkowitz; Robert J. (Durham, NC), Piantadosi; Claude A. (Durham, NC), Stamler; Jonathan S. (Chapel Hill, NC), Whalen; Erin J. (Durham, NC) Assignee(s): Duke University (Durham, NC) Patent Number: 6,627,602 Date filed: October 25, 2002 Abstract: Desensitization of receptors that control disease is prevented by inhibiting Gprotein receptor kinases. This has applicability, e.g., for patients with heart failure or on a left ventricular heart device or a heart pump after surgery or about to undergo surgery and at high risk for a cardiac event or on an opiate or addicted to opiate or with cystic fibrosis or rheumatoid arthritis. Excerpt(s): Many receptors which are involved in controlling pathologic conditions are coupled to G-proteins (Pierce, K. L., et al, Nature Review (Molecular Cell Biology) 3, 639-650 (2002)). These are called G-protein coupled receptors (GPCRs). The GPCRs include.alpha.-adrenergic receptors,.beta.-adrenergic receptors, opioid receptors and prostaglandin receptors. Over time, when agonists are administered to activate the receptors, the receptors become desensitized, i.e., agonist administration no longer results in therapeutic activation of receptors and the receptors regardless of agonist administration are unable to control the pathologic condition. It is known that when agonist binds to a GPCR to activate it, the sequence of events is that the receptor is phosphorylated, the phosphorylated receptor moves to the interior of the cell it is associated with, i.e., it is internalized, with the internalization often involving recruitment of.beta.-arrestin and then the receptor is recycled and moves to the surface of the cell housing it where it is available to control a disease event and to bind to agonist for activation for control of the disease event. The GPCRs have G-protein receptor kinases (GRKs) associated with them. The GRKs phosphorylate agonistoccupied receptors thereby promoting binding of.beta.-arrestin molecules which inhibit interactions between the receptors and G-proteins while also promoting internalization of the receptors. GRKs thus dampen signaling by the GPCRs. The typical response is decreased level of GPCRs and desensitization thereof (i.e., inability of agonist to activate the receptor and inability of the GPCRs to control the disease event). It has been discovered herein that nitric oxide donors (NO donors) that donate nitric oxide or a related redox species and provide bioactivity that is identified with nitric oxide, preferably S-nitrosoglutathione (GSNO), inhibit the GRKs dramatically thereby allowing GPCRs to signal and to be recycled to the cell surface, i.e., thus preventing desensitization of the GPCRs and allowing GPCRs to be available in sufficient amount to control the disease event. It has also been discovered herein that administration of GSNO results in growth of heart muscle (hypertrophy) in vivo (which can be both dependent and independent of expression of receptors) and prevents cardiac.beta.adrenergic receptor down regulation after chronic administration of a.beta.-adrenergic agonist. The above discoveries support the invention herein which is directed to a method for treating a patient with a disease or pathologic condition associated with Gprotein receptor kinase activity where the G-protein receptor kinase activity would otherwise cause desensitization of a receptor controlling said disease or condition, said method comprising the step of administering NO donor that donates nitric oxide or a related redox species and provides bioactivity that is identified with nitric oxide to inhibit the G-protein receptor kinase activity, thereby sensitizing or preventing desensitization of said receptor.
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Web site: http://www.delphion.com/details?pn=US06627602__ •
Reagents and methods for detection of heart failure Inventor(s): Adam; Gail Isabel Reid (Knivsta, SE), Andersson; Maria Kristina (Uppsala, SE), Berglund; Lars Gunnar Ture (Uppsala, SE), Reneland; Rikard Henry (Uppsala, SE) Assignee(s): Sequenom-Gemini Limted (Stockport, GB) Patent Number: 6,528,268 Date filed: August 3, 2001 Abstract: The invention provides novel reagents, kits, and methods for diagnosis of predisposition to left ventricular heart failure, based on analysis of polymorphic variants of the genomic nucleic acid set forth in SEQ ID NO:1 Excerpt(s): The present invention relates to oligonucleotides, kits, microarrays, and methods for detection of cardiovascular disease, in particular, left ventricular heart failure. The World Health Organization has determined that cardiovascular disease (CVD) is the leading cause of death throughout the world and the leading cause of lost years of healthy life in Europe. In the U.S., CVD caused 41 per cent of all deaths in 1998 and is second only to all cancers combined in years of potential life lost. The annual number of deaths from CVD in the U.S. increased substantially between 1900 and 1970, peaking in 1963. Since 1963 the U.S. CVD death rate has changed from an increasing to a decreasing trend, and by 1995 the CVD death rate was similar to that in 1936. The only exception to the CVD mortality decline in the U.S. is congestive heart failure (CHF). CHF is often the end stage of cardiac disease, and half of the patients diagnosed with CMF die within five years. Sudden death is common among CHF patients, occurring six to nine times more frequently than in the general population. Between 1968 and 1998, the number of deaths from CHF in the U.S. increased from approximately 10,000 to almost 50,000. Approximately five million Americans are currently living with heart failure, and 550,000 new cases are diagnosed in the U.S. each year. CHF occurs slightly more frequently among men than among women, and is twice as common among African Americans compared to Caucasian Americans, with mortality also doubled for African Americans. The number of CHF cases is expected to increase as the population ages, and as cardiac patients are able to survive and live longer with their disease. CMF has therefore become a major medical problem in the U.S. Web site: http://www.delphion.com/details?pn=US06528268__
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Stable compositions comprising levosimendan and alginic acid Inventor(s): Backman; Maarit (Helsinki, FI), Larma; Ilkka (Springfield, NJ) Assignee(s): Orion Corporation (Espoo, FI) Patent Number: 6,531,458 Date filed: December 6, 2000 Abstract: The present invention relates to pharmaceutical compositions of levosimendan comprising alginic acid for improving the stability of levosimendan in the compositions. Levosimendan is useful in the treatment of congestive heart failure. Excerpt(s): The present invention relates to pharmaceutical compositions, particularly for oral administration, with improved stability comprising levosimendan, the (-)
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enantiomer of [[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]pro panedinitrile, as the active ingredient. Levosimendan is useful in the treatment of congestive heart failure. The hemodynamic effects of levosimendan in man are described in Sundberg, S. et al., Am. J. Cardiol., 1995; 75: 1061-1066. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S57-S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients. The preparation of pharmaceutical compositions of levosimendan, particularly for oral use, has proved to be difficult. When combined with conventional excipients levosimendan shows poor stability and easily degrades under storage conditions. Therefore, there is a need for pharmaceutical preparations of levosimendan which show improved stability of the active ingredient under storage. Web site: http://www.delphion.com/details?pn=US06531458__ •
System and method for evaluating risk of mortality due to congestive heart failure using physiologic sensors Inventor(s): Bradley; Kerry (Glendale, CA), Kroll; Mark W. (Simi Valley, CA) Assignee(s): Pacesetter, Inc. (Sylmar, CA) Patent Number: 6,645,153 Date filed: February 7, 2002 Abstract: A congestive heart failure (CHF) mortality risk metric is automatically generated using an implantable medical device and, if it exceeds a predetermined threshold, a warning signal is issued indicating a significant risk of mortality due to CHF, perhaps necessitating more aggressive medical therapy. The CHF mortality risk metric is calculated based on a combination of estimated ventilatory response values and the slope of heart rate reserve as a function of predicted heart rates. Ventilatory response is estimated based on detected values of actual heart rate, arterial oxygen saturation, right ventricular O.sub.2, stroke volume, tidal volume, and respiration rate. Heart rate reserve values are derived from the actual heart rate along with patient age and rest heart rate. The predicted heart rates, which represent the heart rates the patient would achieve if healthy, are derived from activity sensor signals. The CHF mortality risk metric is then calculated as a ratio of ventilatory response and the slope of the heart rate reserve. If the CHF mortality risk metric exceeds a critical threshold value, such as 90, the warning signal is generated. Also described herein are various techniques for estimating ventilatory response. Excerpt(s): The invention relates generally to an implantable cardiac stimulation device for the purpose of monitoring the progression of congestive heart failure or the efficacy of delivered heart failure therapies. Congestive heart failure (CHF) is a debilitating, end-stage disease in which abnormal function of the heart leads to inadequate blood flow to fulfill the needs of the body's tissues. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately fill with blood between heartbeats and the valves regulating blood flow become leaky, allowing regurgitation or back flow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness, and inability to carry out daily tasks may result. Not all CHF patients suffer debilitating symptoms immediately. Some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive. As CHF progresses, it tends to become increasingly
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difficult to manage. Even the compensatory responses it triggers in the body may themselves eventually complicate the clinical prognosis. For example, when the heart attempts to compensate for reduced cardiac output, it adds muscle causing the ventricles to grow in volume in an attempt to pump more blood with each heartbeat. This places a still higher demand on the heart's oxygen supply. If the oxygen supply falls short of the growing demand, as it often does, further injury to the heart may result. The additional muscle mass may also stiffen the heart walls to hamper rather than assist in providing cardiac output. Web site: http://www.delphion.com/details?pn=US06645153__ •
Treatment of congestive heart failure Inventor(s): Smith; Eldon R. (Calgary, CA), Torre-Amione; Guillermo (Bellaire, TX) Assignee(s): Vasogen Ireland Limited (Shannon, IE) Patent Number: 6,572,895 Date filed: January 17, 2001 Abstract: A method of treating congestive heart failure (CHF) in a human patient comprises treating an aliquot of the patient's blood ex vivo with at least one stressor selected from the group consisting of a temperature above or below body temperature, an electromagnetic emission and an oxidative environment, followed by administering the aliquot of treated blood to the patient. The treatment can be used on its own or as an adjunctive therapy in combination with conventional CHF treatments. Excerpt(s): This invention relates to methods for treating congestive heart failure, in particular by the administration to a human subject of an aliquot of modified blood, optionally in combination with one or more other treatments for alleviating the symptoms of congestive heart failure. Congestive heart failure (CHF) is a relatively common disorder affecting approximately five million Americans, with a mortality rate of over 80,000 per year. It is believed that CHF is not a distinct disease process in itself, but rather represents the effect of multiple anatomic, functional and biologic abnormalities which interact together to ultimately produce progressive loss of the ability of the heart to fulfill its function as a circulatory pump. Some of the more important pathophysiologic changes which occur in CHF are activation of the hypothalamic-pituitary-adrenal axis, systemic endothelial dysfunction and myocardial remodeling. Web site: http://www.delphion.com/details?pn=US06572895__
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Treatment of congestive heart failure and autonomic cardiovascular drive disorders Inventor(s): Adkins; Robert A. (Angleton, TX), Barrett; Burke T. (Houston, TX), Terry, Jr.; Reese S. (Houston, TX) Assignee(s): Cyberonics, Inc. (Houston, TX) Patent Number: 6,622,041 Date filed: August 21, 2001 Abstract: A device for treating patients suffering from congestive heart failure includes an implantable neurostimulator for stimulating the patient's vagus nerve at or above the cardiac branch with an electrical pulse waveform at a stimulating rate sufficient to
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maintain the patient's heart beat at a rate well below the patient's normal resting heart rate, thereby allowing rest and recovery of the heart muscle, to increase in coronary blood flow, and/or growth of coronary capillaries. A metabolic need sensor detects the patient's current physical state and concomitantly supplies a control signal to the neurostimulator to vary the stimulating rate. If the detection indicates a state of rest, the neurostimulator rate reduces the patient's heart rate below the patient's normal resting rate. If the detection indicates physical exertion, the neurostimulator rate increases the patient's heart rate above the normal resting rate. Excerpt(s): It is currently estimated that some five million Americans suffer from congestive heart failure (CHF), a condition of abnormally low cardiac output. More than one million of these afflicted persons are under age 60. An increasing rate of CHF sufferers may be regarded as a sign of progress in the field of cardiology, since it stems in large measure from saving the lives of heart attack victims and patients with other heart problems. But many of the survivors are left with CHF, in which a markedly reduced cardiac output leads to an inability of the heart to maintain the body's need for oxygen-rich blood circulation. As many as 40 percent of CHF patients are at risk of sudden death. Another fourteen million Americans are diabetic and forty million more exhibit hypertension (persistent elevated blood pressure). A considerable percentage of patients with diabetic neuropathy, hypertension and other pathologies affecting the nervous system are also at higher risk of sudden death. Diseases such as CHF, hypertension and diabetes are characteristically associated with an increased autonomic cardiovascular drive (see, e.g., Blood Pressure 1998; Suppl 3:5-13). In addition, increased autonomic cardiovascular drive has been associated with myocardial infarction, cardiac transplantation, tetraplegia and anxiety disorders (Circulation 1996; 93:1043-1065, Bio Psychol March 1998; 47(3):243-63). "Tone" is the output that emanates from the central nervous system via sympathetic and parasympathetic efferent nerves. The overall "drive" depends on the balance between inhibitory (parasympathetic or vagal) and excitatory (sympathetic) tone and the responsiveness of the organ of interest to that tone. Responsiveness, in turn, depends on the receptor's properties as well as on the intrinsic functional or anatomic properties of the responding organ. An enhanced autonomic drive, independent of the underlying condition, greatly increases the risk of poor cardiovascular outcomes. It follows that targeting the underlying autonomic imbalance in congestive heart failure, hypertension and diabetes may not only be pathophysiologically sound but may also lead to better outcomes (Juilius, Blood Press 1998; Suppl 3:5-13). Web site: http://www.delphion.com/details?pn=US06622041__ •
Use of angiotensin I derivatives as an agent for the treatment and prevention of infarction-related cardiac injuries and disorders Inventor(s): Sim; Meng Kwoon (Singapore, SG) Assignee(s): National University of Singapore (Singapore, SG) Patent Number: 6,589,938 Date filed: June 29, 2001 Abstract: The present invention relates generally to a method for the treatment and/or prophylaxis of infarction-related cardiac injuries and disorders. More particularly, the present invention contemplates a method for the treatment and/or prophylaxis of myocardial infarction and heart failure and/or related conditions. The method of the present invention is practised by the administration of a derivative of angiotensin I. In a
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preferred embodiment, the angiotensin I is des-Aspartate-angiotensin I. The present invention further contemplates compositions for use in the treatment and/or prophylaxis of infarction-related cardiac injuries and disorders such as but not limited to myocardial infarction and heart failure. Excerpt(s): The present invention relates to the use of angiotensin I derivatives, including des-Aspartate angiotensin I in the treatment and/or prevention of infarctionrelated cardiac injuries and disorders. More particularly, the present invention contemplates a method for the treatment and/or prevention of myocardial infarction, heart failure and/or related conditions. The present invention further contemplates compositions for use in the treatment and/or prophylaxis of infarction-related cardiac injuries and disorders such as but not limited to myocardial infarction and heart failure. Infarction or necrosis of part of the heart muscle can lead to various conditions including ischemia of cardiac tissue, angina, arrhythmia, cardiac hypertrophy, and heart failure. Extensive infarction or enlargement of infarction may result in cardiac arrest and death. Cardiac or myocardial infarction and related injuries and disorders contribute to significant morbidity and mortality in patients affected by such conditions. Des-Aspartate angiotensin I (des-Asp-angiotensin I) is a nonapeptide produced from a decapeptide by the action of an aminopeptidase. The nonapeptide is produced from angiotensin I by enzymatic NH.sub.2 -terminal degradation (1). Des-Asp-angiotensin I is a substrate for plasma and pulmonary angiotensin converting enzyme (2). U.S. Pat. No. 5,773,415 discloses the attenuating effect of des-Asp-angiotensin I on experimentally induced non-infarction-related cardiac hypertrophy in rat. In U.S. Pat. No. 6,100,237, the use of des-Asp-angiotensin I as an anti-neointima and anti-arteriosclerotic agent is disclosed. It appears des-Asp-angiotensin I act on a specific indomethacin and losartansensitive subtype of angiotensin receptor AT.sub.1 (3) to antagonize the pressor (4) and hypertrophic (5, 6) actions of angiotensin II. AT.sub.1 is one of the two specific angiotensin receptors, the activation of which is related to the effect of angiotensin II on cardiac tissue (7). Web site: http://www.delphion.com/details?pn=US06589938__ •
Use of leukemia inhibitory factor and endothelin antagonists Inventor(s): Ferrara; Napoleone (San Francisco, CA), King; Kathleen (Pacifica, CA), Luis; Elizabeth (San Francisco, CA), Mather; Jennie P. (Millbrae, CA), Paoni; Nicholas F. (Belmont, CA) Assignee(s): Genentech, Inc. (South San Francisco, CA) Patent Number: 6,653,287 Date filed: September 13, 2000 Abstract: A leukemia inhibitory factor antagonist, alone or in combination with an endothelin antagonist, may be used for treatment of heart failure. The antagonist(s) are administered in a chronic fashion, in therapeutically effective amounts, to achieve this purpose. Excerpt(s): This application relates to a method for modulating cardiac function in the treatment of heart disorders. Heart failure affects approximately three million Americans, developing in about 400,000 each year. It is currently one of the leading admission diagnoses in the U.S. Recent advances in the management of acute cardiac diseases, including acute myocardial infarction, are resulting in an expanding patient population that will eventually develop chronic heart failure. Current therapy for heart
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failure is primarily directed to using angiotensin-converting enzyme (ACE) inhibitors and diuretics. While prolonging survival in the setting of heart failure, ACE inhibitors appear to slow the progression towards end-stage heart failure, and substantial numbers of patients on ACE inhibitors have functional class III heart failure. Moreover, ACE inhibitors consistently appear unable to relieve symptoms in more than 60% of heart failure patients and reduce mortality of heart failure only by approximately 1520%. Heart transplantation is limited by the availability of donor hearts. Further, with the exception of digoxin, the chronic administration of positive inotropic agents has not resulted in a useful drug without accompanying adverse side effects, such as increased arrhythmogenesis, sudden death, or other deleterious side effects related to survival. These deficiencies in current therapy suggest the need for additional therapeutic approaches. Web site: http://www.delphion.com/details?pn=US06653287__
Patent Applications on Heart Failure As of December 2000, U.S. patent applications are open to public viewing.7 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 heart failure: •
2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives Inventor(s): Barrett, Stephen Douglas; (Livonia, MI), Bridges, Alexander James; (Saline, MI), Cody, Donna Reynolds; (Saline, MI), Doherty, Annette Marian; (Paris, FR), Dudley, David Thomas; (Ann Arbor, MI), Saltiel, Alan Robert; (Ann Arbor, MI), Schroeder, Mel Conrad; (Dexter, MI), Tecle, Haile; (Ann Arbor, MI) Correspondence: Warner-lambert Company; 2800 Plymouth RD; Ann Arbor; MI; 48105; US Patent Application Number: 20030149015 Date filed: December 10, 2002 Abstract: Phenylamino benzoic acid, benzamides, and benzyl alcohol derivatives of the formula 1where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are hydrogen or substituent groups such asalkyl, and where R.sub.7 is hydrogen or an organic radical, and Z is COOR.sub.7, tetrazolyl, CONR.sub.6R.sub.7, or CH.sub.2OR.sub.7, are potent inhibitors of MEK and, as such, are effective in treating cancer and other proliferative diseases such as inflammation, psoriasis and restenosis, as well as stroke, heart failure, and immunodeficiency disorders. Excerpt(s): This invention provides benzoic acid and amide derivatives of anthranilic acids which inhibit certain dual specificity kinase enzymes involved in proliferative diseases such as cancer and restenosis. Proliferative diseases are caused by a defect in the intracellular signaling system, or the signal transduction mechanism of certain proteins. Cancer, for example, is commonly caused by a series of defects in these signaling proteins, resulting from a change either in their intrinsic activity or in their cellular concentrations. The cell may produce a growth factor that binds to its own receptors, resulting in an autocrine loop, which continually stimulates proliferation.
7
This has been a common practice outside the United States prior to December 2000.
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Mutations or overexpression of intracellular signaling proteins can lead to spurious mitogenic signals within the cell. Some of the most common mutations occur in genes encoding the protein known as Ras, which is a G-protein that is activated when bound to GTP, and inactivated when bound to GDP. The above mentioned growth factor receptors, and many other mitogenic receptors, when activated, lead to Ras being converted from the GDP-bound state to the GTP-bound state. This signal is an absolute prerequisite for proliferation in most cell types. Defects in this signaling system, especially in the deactivation of the Ras.GTP complex, are common in cancers, and lead to the signaling cascade below Ras being chronically activated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
A1 adenosine receptro antagonists Inventor(s): Lin, Ko-Chung; (Lexington, MA), Vu, Chi; (Arlington, MA) Correspondence: Fish & Neave; 1251 Avenue OF The Americas; 50th Floor; New York; NY; 10020-1105; US Patent Application Number: 20030220358 Date filed: May 27, 2003 Abstract: Compounds of Formula I and II are disclosed as antagonists of subtype A1 adenosine receptors. These compounds are useful for treatment of various diseases and disorders, including systemic hypertension, renal failure, diabetes, asthma, an edematous condition, congestive heart failure, and renal dysfunction. 1 Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/250,658, filed Dec. 1, 2000, which is herein incorporated by reference. This invention relates to medicinal chemistry and pharmacology. More particularly, it relates to antagonists of the adenosine receptors, pharmaceutical compositions comprising these compounds and methods of making and using the same in the treatment of diseases. Adenosine is a ubiquitous biochemical messenger. Adenosine binds to and activates seven-transmembrane spanning G-protein coupled receptors, eliciting a variety of physiological responses. Adenosine receptors are divided into four known subtypes (i.e., A.sub.1, A.sub.2a, A.sub.2b, and A.sub.3). These receptor subtypes mediate different, and sometimes opposing, effects. Activation of the adenosine A.sub.1 receptor, for example, elicits an increase in renal vascular resistance, while activation of the adenosine A.sub.2a receptor elicits a decrease in renal vascular resistance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Aldosterone receptor antagonist and alpha-adrenergic modulating agent combination therapy for prevention or treatment of pathogenic conditions Inventor(s): McMahon, Ellen G.; (Sunset Hills, MO), Rudolph, Amy; (St. Louis, MO) Correspondence: Pharmacia Corporation; Global Patent Department; Post Office Box 1027; ST. Louis; MO; 63006; US Patent Application Number: 20030199483 Date filed: January 30, 2003 Abstract: A combination therapy comprising a therapeutically-effective amount of an aldosterone receptor antagonist and a therapeutically-effective amount of an alpha-
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adrenergic modulating agent is described for treatment of circulatory disorders, including cardiovascular disorders such as hypertension, congestive heart failure, cirrhosis and ascites. Preferred alpha-adrenergic modulating agents are those compounds having high potency and bioavailability. Preferred aldosterone receptor antagonists are 20-spiroxane steroidal compounds characterized by the presence of a 9.alpha.,11.alpha.-substituted epoxy moiety. A preferred combination therapy includes an alpha-1-adrenergic antagonist or an alpha-2-adrenergic agonist and the aldosterone receptor antagonist epoxymexrenone. Excerpt(s): Combinations of an aldosterone receptor antagonist and an alpha-adrenergic modulating agent are described for use in prevention or treatment of pathogenic conditions, including circulatory disorders encompassing cardiovascular diseases such as hypertension, heart failure (including congestive heart failure), cardiac hypertrophy, cirrhosis and ascites. Of particular interest are therapies using an epoxy-containing steroidal aldosterone receptor antagonist compound such as epoxymexrenone in combination with either an alpha-1-adrenergic antagonist compound or an alpha-2adrenergic agonist compound. Myocardial (or cardiac) failure, whether a consequence of a previous myocardial infarction, heart disease associated with hypertension, or primary cardiomyopathy, is a major health problem of worldwide proportions. The incidence of symptomatic heart failure has risen steadily over the past several decades. In clinical terms, decompensated cardiac failure consists of a constellation of signs and symptoms that arises from congested organs and hypoperfused tissues to form the congestive heart failure (CHF) syndrome. Congestion is caused largely by increased venous pressure and by inadequate sodium (Na.sup.+) excretion, relative to dietary Na.sup.+ intake, and is importantly related to circulating levels of aldosterone (ALDO). An abnormal retention of Na.sup.+ occurs via tubular epithelial cells throughout the nephron, including the later portion of the distal tubule and cortical collecting ducts, where ALDO receptor sites are present. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cardiac-specific 11beta hydroxysteroid dehydrogenase type 2 transgenic mice Inventor(s): Goellner, Joseph; (St. Charles, MO), McMahon, Ellen G.; (St. Louis, MO), Qin, Wenning; (Ballwin, MO), Rudolph, Amy E.; (St. Louis, MO) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030221207 Date filed: February 11, 2003 Abstract: Five independent transgenic founder lines were created which have all developed cardiac hypertrophy and heart failure. The line with the most severe phenotype was analyzed in detail. Transgenic cardiac 11.beta.HSD2 mRNA expression is increased 4,000 fold over non-transgenic mice and the expressed enzyme was found to possess catalytic activity. At five months of age transgenic mice had developed severe myocardial hypertrophy in the absence of an increase in blood pressure. Interstitial fibrosis in the left ventricle of transgenic mice was revealed by picrosirius red staining. The hearts of the mice were severely dilated and cardiomyocyte size was increased. Excerpt(s): This application claims the benefit of provisional application Ser. No. 60/355,812 filed Feb. 13, 2002. The disclosure of the provisional application is expressly incorporated herein in its entirety. A portion of the disclosure of this patent document
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contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. The invention relates to the field of cardio therapeutics. In particular, it relates to a model system for identifying and developing new drugs for treating cardiac failure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Catecholamine pharmaceutical compositions and methods Inventor(s): Dillon, Patrick F.; (East Lansing, MI), Root-Bernstein, Robert S.; (East Lansing, MI) Correspondence: Harness, Dickey & Pierce, P.L.C.; P.O. Box 828; Bloomfield Hills; MI; 48303; US Patent Application Number: 20030216413 Date filed: March 28, 2003 Abstract: Pharmaceutical compositions and method using adrenergic compounds and complement compounds. Compositions are provided comprising:(c) a subefficacious amount of an adrenergic compound; and(d) a safe and effective amount of a complement to the adrenergic compound.Methods are also provided comprising the administration of:(c) a low dose of an adrenergic compound; and(d) a safe and effective amount of a complement to said adrenergic compound.Preferably, the adrenergic compound is a catecholamine. Complements include ascorbates, opioids, polycarboxylic acid chelaters, and mixtures thereof. Preferred complements include ascorbates, particularly ascorbic acid. Methods include the treatment of neurological disorders, hypotension, forward failure, backward failure, congestive heart failure, shock, hypertension, hemorrhage, disorders associated with anesthesia, chronic obstructive pulmonary disease, asthma, colic, Crohn's disease, anaphylaxis, interstitial cystitis, overactive bladder syndrome, premature labor, myethsenia gravis, and glaucoma. Excerpt(s): This application is a continuation-in-part of International Application PCT/US01/30272, with an international filing date of Sep. 27, 2001, published in English under PCT Article 21(2), which claims the benefit of U.S. Provisional Application No. 60/236,751, filed Sep. 29, 2000. This invention relates to novel methods of treating disorders mediated by adrenergic receptors, and novel pharmaceutical compositions containing catecholamines or other adrenergic compounds. For example, the compositions and methods of this invention comprise the use of catecholamines and ascorbates in the treatment of a variety of disorders, including asthma, hypertension, and congestive heart failure. Catecholamines and related adrenergic (sympathomimetic) drugs are involved in the regulation of a wide variety of body functions. Such compounds have their effect directly or indirectly on the alpha- and beta-adrenergic receptors found in tissues throughout the body. Because the functions that are mediated by these receptors are diverse, agents that agonize or antagonize their activity are useful in the treatment of a variety of clinical disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combinations Inventor(s): Cohen, David Saul; (New Providence, NJ) Correspondence: Thomas Hoxie; Novartis, Patent And Trademark Department; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030139429 Date filed: September 6, 2002 Abstract: The present invention relates to a pharmaceutical composition, comprising(a) a phosphodiesterase 5 inhibitor or a pharmaceutically acceptable salt thereof and(b) at least one of the active ingredients selected from the group consisting of(i) an antidiabetic agent;(ii) HMG-Co-A reductase inhibitors;(iii) an anti-hypertensive agent; and(iv) a serotonin reuptake inhibitor (SSRI)or, in each case, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. The pharmaceutical composition may be employed for the treatment of sexual dysfunction, hyperglycemia, hyperinsulinaemia, hyperlipidaemia, hypertriglyceridemia, diabetes, insulin resistance, impaired glucose metabolism, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, obesity, diabetic retinopathy, diabetic nephropathy, glomerulosclerosis, diabetic neuropathy, syndrome X, erectile dysfunction, coronary heart disease, hypertension, especially ISH, angina pectoris, myocardial infarction, stroke, vascular restenosis, endothelial dysfunction, impaired vascular compliance, congestive heart failure. Excerpt(s): and a pharmaceutically acceptable carrier. R.sup.6 and R.sup.7 are each independently hydrogen or alkyl optionally substituted by hydroxy or alkoxy or one of R.sup.6 and R.sup.7 is hydrogen and the other is acyl, or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached denote a 5- or 6- membered heterocyclyl group. "Alkyl" as used herein denotes straight chain or branched alkyl, which may be, for example, C.sub.1-C.sub.10-alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, straight or branched pentyl, straight or branched hexyl, straight or branched heptyl, straight or branched octyl, straight or branched nonyl or straight or branched decyl. Preferably alkyl is C.sub.1-C.sub.8-alkyl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Composition for the treatment of heart failure Inventor(s): Aass, Halfdan; (Oslo, NO), Andreassen, Arne; (Oslo, NO), Aukrust, Pal; (Oslo, NO), Fjeld, Jan; (Oslo, NO), Froland, Stig; (Oslo, NO), Gullestad, Lars; (N-Baerum Post-Terminal, NO), Ihlen, Halfdan; (Oslo, NO), Kjekshus, John; (Oslo, NO), Lien, Egil; (Trondheim, NO), Nitter-Hauge, Sigurd; (Oslo, NO), Simonsen, Svein; (Oslo, NO), Ueland, Thor; (Oslo, NO) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030170241 Date filed: February 20, 2003 Abstract: The present invention relates to the use of an immunomodulating agent, in particular intravenous immunoglobulin (IVIG), in the manufacture of a medicament for use in the treatment of non-viral or non-autoimmune induced heart disorders or nonviral or non-autoimmune associated phases of heart disorders or the symptoms
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associated therewith. Particular heart disorders to be treated are selected from the group comprising chronic CHF, chronic (stable) angina pectoris and acute coronary syndromes. Pharmaceutical compositions for use in the treatment of such disorders comprising immunomodulating agents are also provided. Excerpt(s): The present invention relates to heart disorders and in particular the use of immunomodulating agents for the treatment of heart disorders and the symptoms associated therewith. Heart disorders or diseases, which are generally characterised by impaired cardiac function, e.g. heart failure affect a large number of people worldwide and in particular in the Western world. Heart disorders or diseases are responsible for a reduced quality of life and premature death in a significant proportion of sufferers. Heart disorders occur in men, women, and children of both sexes, but are particularly prevalent in men and in elderly or middle aged people. Heart failure is characterized by impaired cardiac function either due to reduced pump function (systolic dysfunction) or reduced filling (diastolic dysfunction). There are a number of different causes of heart failure of which the most common in the western world is coronary artery disease. Other common causes are cardiomyopathy (primary or secondary), hypertension, valvular diseases, and congenital defects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for treating heart failure Inventor(s): Elias, Kathleen A.; (San Francisco, CA), Feng, Bainian; (Foster City, CA), Lu, Pu-Ping; (Foster City, CA), Malik, Fady; (Burlingame, CA), Morgan, Bradley Paul; (Moraga, CA), Morgans, David J. JR.; (Los Altos, CA), Qian, Xiangping; (Foster City, CA), Smith, Whitney Walter; (El Cerrito, CA), Tomasi, Adam Lewis; (San Francisco, CA), Zhou, Han-Jie; (Foster City, CA) Correspondence: David A. Lowin; P.O. Box 620535; Woodside; CA; 94062-0535; US Patent Application Number: 20030158186 Date filed: December 20, 2002 Abstract: Certain substituted benzamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure. Excerpt(s): This application claims the benefit of co-pending provisional U.S. Application Serial No. 60/343,092, filed Dec. 21, 2001, incorporated herein by reference. The invention relates to N-sulfonyl-heterocyclyl-sulfonamide derivatives and substituted N-sulfonyl-aminoalkyl-sulfonamide derivatives, particularly to compounds that selectively modulate the cardiac sarcomere, and specifically to compounds, pharmaceutical formulations and methods of treatment for systolic heart failure, including congestive heart failure. The "sarcomere" is an elegantly organized cellular structure found in cardiac and skeletal muscle made up of interdigitating thin and thick filaments; it comprises nearly 60% of cardiac cell volume. The thick filaments are composed of "myosin," the protein responsible for transducing chemical energy (ATP hydrolysis) into force and directed movement. Myosin and its functionally related cousins are called motor proteins. The thin filaments are composed of a complex of proteins. One of these proteins, "actin" (a filamentous polymer) is the substrate upon which myosin pulls during force generation. Bound to actin are a set of regulatory proteins, the "troponin complex" and "tropomyosin," which make the actin-myosin interaction dependent on changes in intracellular Ca.sup.2+ levels. With each heartbeat,
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Ca.sup.2+ levels rise and fall, initiating cardiac muscle contraction and then cardiac muscle relaxation (Robbins J and Leinwand L A. (1999) Molecular Basis of Cardiovascular Disease, Chapter 8. editor Chien, K. R., W. B. Saunders, Philadelphia). Each of the components of the sarcomere contributes to its contractile response. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Congestive heart failure monitor Inventor(s): Alt, Eckhard; (Ottobrunn, DE) Correspondence: Donald R. Greene; P.O. Box 12995; Scottsdale; AZ; 85267; US Patent Application Number: 20030220580 Date filed: May 25, 2002 Abstract: A device-implemented method is disclosed for early detection and monitoring of congestive heart failure in a patient. Ongoing measurements of impedance of a portion of the patient's body generally occupied by the lungs are performed by an implanted device, and, when the impedance measurements are determined by internal circuit components of the device to exceed a predetermined threshold value indicative of a need for immediate attention to a condition of congestive heart failure, a patient and/or physician alert is emitted by the device. An implant site at the left lower anterior lateral hemithorax is preferred. Excerpt(s): The present invention relates generally to implantable medical devices, and more particularly to an implantable device for detecting and monitoring the progression of congestive heart failure. Many patients who have suffered one or more myocardial infarctions subsequently require treatment for congestive heart failure (CHF). The left heart fails while the pumping function of the right heart remains adequate, because the latter has only about 20% of the workload of the former. This leads to an increase in blood volume congested to the lungs, resulting in pulmonary congestion, build up of edema, and congestion of internal organs including the stomach and intestines. Increased fluid in the stomach and intestines reduce their ability to absorb drugs prescribed for treatment of CHF, particularly diuretics. The congestion is often accompanied by a worsening of myocardial function, with consequent drop in blood pressure and reduced renal perfusion, which only further aggravates the congestive situation. Thus, late recognition of congestion leads to increased dosages of oral diuretics that are unsuccessful to treat the condition, ultimately requiring that the patient be hospitalized. Avoidance of hospitalization and the pitfalls of late treatment require detection of CHF at an early stage, so that the prescribed drugs can be fully absorbed and effective. If detected early, a combination of diuretics and other drugs can slow the progress of the disease and allow the patient to enjoy an improved lifestyle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Core body temperature monitoring in heart failure patients Inventor(s): Spinelli, Julio; (Shoreview, MN), Zhu, Qingsheng; (Little Canada, MN) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030220582 Date filed: May 22, 2002 Abstract: An implanted heart monitor includes sensors that measure various aspects of the heart failure patient's heart. A remote heart monitoring system connects the implanted heart monitor to a care provider, such as a physician. The data provided by the implanted heart monitor permits the care provider to obtain valuable data on the heart in order to make health care decisions affecting the heart failure patient's treatment. In many cases, the measurement of core body temperature and other patient data will enable the care provider to alter the patient's treatment to address the patient's condition. The implanted heart monitor can communicate over a wireless communication link with an external monitor. The implanted heart monitor may be implemented as part of a pacing device (i.e., pace maker) or may be a separate unit devoted to monitoring functions. The external monitor communicates with a monitoring station over a communication link. The monitoring station can operate as a centralized data collection unit, collecting data from multiple external monitors and multiple implanted heart monitors. Various other aspects of a heart failure patient's heart and/or body can be monitored, such as heart rate, blood pH levels, blood CO.sub.2 levels, and any other indications of the heart failure patient's activity. Various predetermined thresholds may be set to trigger alarms and/or data reports. Excerpt(s): The present invention relates to monitoring heart performance in heart failure patients. More specifically, the present invention relates to monitoring heart performance to detect the occurrence of a drop in core body temperature in heart failure patients. As early as 1985, medical literature documented a relationship between decreased core body temperature and increased bodily activity in heart failure patients. In a paper by Stanley A. Rubin (RUBIN, STANLEY A. Core body temperature regulation of heart rate during exercise in humans. J. Appl. Physiol. 62(5): 1997-2001, 1987), a significant correlation was found between an observed change in core body temperature and heart rate changes in heart failure patients. Rubin defined core body temperature as the mixed venous blood pool found in the pulmonary artery. Using a thermistor mounted on the distal end of a Swan-Ganz catheter, Rubin found that the core body temperature of heart failure patients decreased during exercise, while the core body temperature in normal patients typically increased during exercise. This relationship between core body temperature and heart activity has been observed in other studies. In a paper by Frank G. Shellock, et al. (SHELLOCK, FRANK G., H. J. C. SWAN, AND STANLEY A. RUBIN. Muscle and femoral vein temperatures during short term maximal exercise in heart failure. J. Appl. Physiol. 58(2): 400-408, 1985), reductions in core body temperatures in heart failure patients were observed while the heart failure patients underwent exercise. Shellock, et al. concluded that the core body temperature decrease observed in heart failure patients is partially caused by the redistribution of cooler blood from the underperfused skeletal muscles into the core blood during exercise. Another paper by Shellock and Rubin (FRANK G. SHELLOCK AND STANLEY A. RUBIN. Mixed venous blood temperature response to exercise in heart failure patients treated with short-term vasodilators. Clinical Physiology 5, 503-514, 1985), also concluded that the core body temperature drop was due to circulatory inadequacies. This conclusion was based on Shellock's and Rubin's conclusion that heart
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failure patients treated with vasodialators experience an attenuation of the core body temperature response typical during exercise, as a result of vasodialator-induced improvement in circulation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Dipeptide derivatives Inventor(s): Carpino, Philip Albert; (Groton, CT), Griffith, David Andrew; (Old Saybrook, CT), Lefker, Bruce Allen; (Gales Ferry, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030216399 Date filed: February 21, 2003 Abstract: This invention is directed to compounds of the formula 1and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis and/or frailty, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis and/or frailty when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-HT920. The invention is also directed to intermediates useful in the preparation of compounds of Formula I. Excerpt(s): This invention relates to dipeptide compounds which are growth hormone secretagogues and are useful for the treatment and prevention of osteoporosis and/or frailty. 3. Increased mobilization of free fatty acids and use of fatty acids for energy. Deficiency in growth hormone results in a variety of medical disorders. In children, it causes dwarfism. In adults, the consequences of acquired GH deficiency include profound reduction in lean body mass and concomitant increase in total body fat, particularly in the truncal region. Decreased skeletal and cardiac muscle mass and muscle strength lead to a significant reduction in exercise capacity. Bone density is also reduced. Administration of exogenous growth hormone has been shown to reverse many of the metabolic changes. Additional benefits of therapy have included reduction in LDL cholesterol and improved psychological well-being. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Endoventicular device for the treatment and correction of cardiomyopathies Inventor(s): Ferrazzi, Paolo; (Bergamo, IT) Correspondence: Mark D Wieczorek; Post Office Box 70072; San Diego; CA; 92167; US Patent Application Number: 20030158570 Date filed: March 31, 2003 Abstract: The invention consists in a device that concerns the optimization of the cardiac geometry in patients with heart failure. The device comprises one or more elastic elements in the radial direction towards the inside of the ventricle and plastic deformation in a direction that is transversal to the said ventricle, the element being equipped with means for attaching it to the internal wall of the ventricle. Excerpt(s): The present invention is aimed at an endoventricular device applicable to patients affected by heart failure due to a cardiomyopathy of different etiologies (idiopathic, ischemic, valvular), with consequent dysfunction and/or dilatation of the left ventricle with or without mitral insufficiency; the invention likewise concerns a system for optimising the diastolic and systolic activity of a heart affected by a cardiomyopathy. In particular, the invention has to do with an endoventricular device that, in case of cardiomyopathy due to mitral insufficiency with annular dilatation, reestablishes annular dimension and in case of other types of cardiomyopathies, without any mass removal, optimises cardiac geometry as an alternative to transplantation and/or mechanical ventricular assistance, in cases in which the said techniques are not indicated. Heart failure is the result of a dysfunction of the heart, particularly cardiac muscle tissue, whose negative effect is that an insufficient blood supply is delivered to the vital organs. This condition of cardiocirculatory insufficiency is a progressive process that can worsen to the point of causing the exitus of the patient. The cardiomyopathies responsible for the dysfunction have various etiologies (viral diseases, idiopathic cardiomyopathy, valvular diseases, ischemic diseases and congenital diseases). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Extensive myocardial infarction model animal, method for preparation there of, and application for drug screening and regenerative medicine Inventor(s): Matsuzaki, Masunori; (Ube-shi, JP), Nakamura, Hiroshi; (Ube-shi, JP), Yoshida, Tsutomu; (Ube-shi, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030213002 Date filed: May 9, 2002 Abstract: The prior art has problems such as high mortality of model animals due to complication of heart failure, necessity of taking into consideration the effects from other organs for investigation of the mechanism of the disease, being unable to prepare an extensive myocardial infarction model, and others. The invention allows exclusion of the state of heart failure and provides an extensive myocardial infarction model animal which permits to prepare a model of the pathology of extensive myocardial infarction.The invention is an extensive myocardial infarction model animal, the method for preparation thereof, and the method for screening of drugs and/or genes using the
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model animal, wherein the heart of a normal animal is extirpated, the left main trunk of the extirpated heart is ligated, the heart after the ligation is heterotopically grafted to the abdomen of another normal animal, and the animal given the heterotopic graft is used as the extensive myocardial infarction model animal. Three weeks after the graft, the model of extensive myocardial infarction pathology is established. Excerpt(s): This invention relates to a novel myocardial infarction model animal, particularly to an extensive myocardial infarction model animal that can exclude the pathological state of heart failure and provides an extensive myocardial infarction model, to the method for preparation thereof, and application for drug screening and regenerative medicine. As a result of Westernization of the lifestyle and eating habits of Japanese, heart diseases, particularly myocardial infarction following coronary occlusion, have been significant medical problems. In general, investigation of the cause and mechanism of diseases including myocardial infarction and efficacy screening tests for verification of drug effect and/or gene transfer on a disease are performed not in normal animals but in disease model animals which are in a certain pathological state. Such disease model animals have been prepared by surgical or medical treatment of normal animals; for example, diabetic model animals prepared by administration of a causative substance as disclosed in the unexamined published Japanese patent application No.2000-270713, pulmonary infection model animals prepared by inoculation of a bacterial suspension through a tube into the animal body as disclosed in the unexamined published Japanese patent application No.2000-262182, and skin ischemia model animals prepared by surgical treatment as disclosed in the unexamined published Japanese patent application No.1999-308941. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Furanone derivatives Inventor(s): Balzo, Ughetta del; (Morgan Hill, CA), Brown, Lesley; (East Palo Alto, CA), Song, Jiangao; (Cupertino, CA), Walkinshaw, Gail; (San Jose, CA), Wang, Bing; (Cupertino, CA), Zhang, Wei; (Santa Clara, CA) Correspondence: Gloria Pfister; 5301 Patrick Henry DR.; Santa Clara; CA; 95054; US Patent Application Number: 20030176361 Date filed: January 28, 2003 Abstract: Furanone derivatives and the pharmaceutically acceptable salts thereof have cytoprotective activity and protective activity for neuroinflammation, and neurodegenerative disorders; they are useful in the treatment of stroke, cerebral ischemia, myocardial infarction, myocardial ischemia, chronic heart failure, inflammation and other oxidative stress-related conditions, as well as Alzheimer's disease and senile dementia; they are also useful in the manufacture of pharmaceutical formulations for the treatment of such conditions. Excerpt(s): This U.S. patent application claims priority under 35 U.S.C. 119(e) to U.S. Provisional Application Serial No. 60/353,939, filed Jan. 31, 2002, incorporated herein by reference in its entirety. The present invention relates to furanone derivatives, particularly to derivatives having cytoprotective activity, especially certain 3-hydroxyfuran-2-one derivatives. The invention is also directed to formulations and methods for treating stroke, myocardial infarction and chronic heart failure, as well as other oxidative stress-related conditions that are typically responsive to cellular enzyme modulation. The invention is also directed to formulations and methods for treating
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neuroinflammation, cognitive disorders and neurodegenerative diseases such as Alzheimer's disease and senile dementia. The present invention deals with certain novel furanone derivatives, which are formed under proper conditions from a series of pyruvate derivatives described in our prior applications, U.S. Ser. No. 10/138,937 and 10/138,032. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Gastrin and cholecystokinin receptor ligands(II) Inventor(s): Buck, Ildiko Maria; (London, GB), Kalindjian, Sarkis Barret; (London, GB), Low, Caroline Minli Rachel; (London, GB), Pether, Michael John; (London, GB), Steel, Katherine Isobel Mary; (London, GB), Tozer, Matthew John; (London, GB), Wright, Paul Trevor; (London, GB) Correspondence: Heller Ehrman White & Mcauliffe Llp; 1666 K Street,nw; Suite 300; Washington; DC; 20006; US Patent Application Number: 20030199565 Date filed: April 7, 2003 Abstract: Substituted imidazoles (1) are useful as angiotensin II blockers. These compounds have activity in treating hypertension and congestive heart failure. Pharmaceutical compositions containing the novel imidazoles and pharmaceutical methods using them, alone and in conjunction with other drugs, especially diuretics and non-steroidal antiinflammatory drugs (NSAID's) are also described. Excerpt(s): This invention relates to gastrin and cholecystokinin (CCK) receptor ligands. (The receptor previously known as the CCK.sub.B/gastrin receptor is now termed the CCK.sub.2 receptor), The invention also relates to methods for preparing such ligands and to compounds which are useful intermediates in such methods. The invention further relates to pharmaceutical compositions comprising such ligands and methods for preparing such pharmaceutical compositions. Gastrin and the cholecystokinins are structurally related neuropeptides which exist in gastrointestinal tissue and the central nervous system (Mutt V., Gastrointestinal Hormones, Glass G. B. J., ed., Raven Press, New York, p. 169; Nisson G., ibid., p. 127). Gastrin is one of the three primary stimulants of gastric acid secretion. Several forms of gastrin are found including 34-, 17- and 14amino acid species with the minimum active fragment being the C-terminal tetrapeptide TrpMetAspPhe-NH.sub.2) which is reported in the literature to have full pharmacological activity (Tracey H. J. and Gregory R. A., Nature (London), 1964, 204, 935). Much effort has been devoted to the synthesis of analogues of this tetrapeptide (and the N-protected derivative Boc-TrpMetAspPhe-NH.sub.2) in an attempt to elucidate the relationship between structure and activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Heart failure treatment device and method Inventor(s): Lau, Lilip; (Los Altos, CA), Patel, Anuja; (Sunnyvale, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030153949 Date filed: October 31, 2002 Abstract: A method and apparatus for treating heart failure is configured to be placed about at least a portion of a patient's heart to apply a mild compressive force on the heart over a range of elastic deformation of the apparatus. The apparatus can be shifted to second range of deformation. In some embodiments, the apparatus is shifted to the second range of deformation by application of a stimulus or alteration of environmental conditions beyond a threshold level. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/335,437, which was filed on Oct. 31, 2001, the entirety of which is hereby incorporated by reference. Congestive heart failure ("CHF") is characterized by the failure of the heart to pump blood at sufficient flow rates to meet the metabolic demand of tissues, especially the demand for oxygen. One characteristic of CHF is remodeling of at least portions of a patient's heart. Remodeling involves physical changes to the size, shape and thickness of the heart wall. For example, a damaged left ventricle may have some localized thinning and stretching of a portion of the myocardium. The thinned portion of the myocardium often is functionally impaired, and other portions of the myocardium attempt to compensate. As a result, the other portions of the myocardium may expand so that the stroke volume of the ventricle is maintained notwithstanding the impaired zone of the myocardium. Such expansion may cause the left ventricle to assume a somewhat spherical shape. Cardiac remodeling often subjects the heart wall to increased wall tension or stress, which further impairs the heart's functional performance. Often, the heart wall will dilate further in order to compensate for the impairment caused by such increased stress. Thus, a vicious cycle can result, in which dilation leads to further dilation and greater functional impairment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Implantable drug delivery system responsive to intra-cardiac pressure Inventor(s): Struble, Chester L.; (Eijsden, NL) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030199813 Date filed: April 22, 2002 Abstract: The invention is directed to techniques for monitoring the condition of a patient, such as a patient having congestive heart failure, and appropriately modifying the patient's drug therapy as a function of a pressure in the patient's heart, such as the estimated pulmonary artery diastolic pressure. The drugs may be administered by an implanted drug delivery device. The drug selection, the drug dosage or both may be controlled as a function of the pressure and/or the activity level of the patient. Excerpt(s): The present invention relates generally to the treatment of congestive heart failure with drugs that increase cardiac output, and more particularly to the treatment
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of congestive heart failure with an implanted drug delivery device. Heart failure refers to the heart's inability to keep up with the demands made upon it. Congestive heart failure refers to an inability of the heart to pump an adequate amount of blood to the body tissues. Because the heart is unable to pump an adequate amount of blood, blood returning to the heart becomes congested in the venous and pulmonary system. In a healthy heart, the heart pumps all of the blood that returns to it, according to the FrankStarling law. Increased venous return leads to increased end diastolic volume, which causes increased strength of contraction and increased stroke volume. In addition to intrinsic control according to the Frank-Starling law, a healthy heart is subject to extrinsic control, such as stimulation by the sympathetic nervous system to enhance contractility. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus of scoring an arterial obstruction Inventor(s): Li, Jianying; (New Berlin, WI) Correspondence: Ziolkowski Patent Solutions Group, Llc (gems); 14135 North Cedarburg Road; Mequon; WI; 53097; US Patent Application Number: 20030215124 Date filed: May 20, 2002 Abstract: The present invention is directed to a method and apparatus of scoring an arterial obstruction. The present invention includes identifying a particular group of pixels corresponding to a calcified region of coronary artery of a patient and based on the satisfaction of a number of thresholds connectivity criteria, determining a calcification score of that calcified region as indicative of the patient's risk of cardiovascular disease including atherosclerosis, heart attack, heart failure, and stroke. The present invention further includes determining the scaling factor unique to a particular imaging slice of data to provide a value of calcium weight and volume that is indicative of the true obstruction and true volume of the calcified region. Excerpt(s): The present invention relates generally to diagnostic imaging and, more particularly, to a method and apparatus of scoring an arterial obstruction. Typically, in computed tomography (CT) imaging systems, an x-ray source emits a fan-shaped beam toward a subject or object, such as a patient or a piece of luggage. Hereinafter, the terms "subject" and "object" may be interchangeably used and shall include anything capable of being imaged. The beam, after being attenuated by the subject, impinges upon an array of radiation detectors. The intensity of the attenuated beam radiation received at the detector array is typically dependent upon the attenuation of the x-ray beam by the subject. Each detector element of the detector array produces a separate electrical signal indicative of the attenuated beam received by each detector element. The electrical signals are transmitted to a data processing system for analysis which ultimately produces an image. Generally, the x-ray source and the detector array are rotated about the gantry within an imaging plane and around the subject. X-ray sources typically include x-ray tubes, which emit the x-ray beam at a focal point. X-ray detectors typically include a collimator for collimating x-ray beams received at the detector, a scintillator for converting x-rays to light energy adjacent the collimator, and photodiodes for receiving the light energy from the adjacent scintillator and producing electrical signals therefrom. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for in vivo regulation of cardiac muscle contractility Inventor(s): Dillmann, Wolfgang H.; (Solana Beach, CA), Giordano, Frank; (Del Mar, CA), Mestril, Ruben; (San Diego, CA) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030211080 Date filed: January 13, 2003 Abstract: A method for regulating in vivo calcium transport in cardiac muscle of animals suffering from congestive heart failure is disclosed. According to the method, calcium ATPase activity (which decreases as congestive heart failure develops) and cardiac muscle contractility augmented by delivering a gene which operatively encodes the enzyme into the heart. Delivery systems, including but not limited to using adenoassociated viral vectors are provided. Methods for monitoring the expression and effect of the gene product on cardiac performance are also provided. Excerpt(s): This is a continuation-in-part of a U.S. application Ser. No. 08/420,306, filed Apr. 11, 1995, still pending. The invention relates to methods for regulating cardiac muscle contractility. More specifically, the invention relates to methods to increase in vivo levels of cardiac sarcoplasmic reticulum (SR) calcium.sup.2++ ATPase (SERCA2) by in vivo delivery of a gene which operatively encodes SERCA2 protein. Congestive heart failure is one of the leading causes of death among adults in the United States. As compared to cardiac ischemia (an acute event resulting from obstruction or loss of blood supply to the heart), congestive heart failure is a relatively insidious event associated with the gradual loss of cardiac muscle contractility and adaptability of the heart to stress. Ultimately, absent effective treatment, the CHF heart loses its ability to pump blood at a rate sufficient to meet the metabolic requirements of the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for treating septic shock Inventor(s): Oldner, Anders; (Sollentuna, SE), Rudehill, Anders; (Bromma, SE), Wanecek, Michael; (Lidingo, SE), Weitzberg, Eddie; (Stockholm, SE) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030158201 Date filed: March 24, 2003 Abstract: Levosimendan, or (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono]propanedinitrile, which has been previously suggested for the treatment of congestive heart failure is useful in the treatment of septic shock. Excerpt(s): The present invention relates to a method for the treatment of septic shock by administering levosimendan, or (-)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3pyridazinyl)phenyl]hydrazono]propanedinitrile (I), or pharmaceutically acceptable salts thereof, to a patient in need of such treatment. The hemodynamic effects of levosimendan in man are described in Sundberg, S. et al., Am. J. Cardiol., 1995; 75: 10611066 and in Lilleberg, J. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S63-S69, 1995. Pharmacokinetics of levosimendan in man after i.v. and oral dosing is described in Sandell, E.-P. et al., J. Cardiovasc. Pharmacol., 26(Suppl.1), S57-S62, 1995. The use of levosimendan in the treatment of myocardial ischemia is described in WO 93/21921.
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The use of levosimendan in the treatment of pulmonary hypertension is described in WO 99/66912. Clinical studies have confirmed the beneficial effects of levosimendan in heart failure patients. Septic shock (also known as sepsis) is the leading cause of morbidity and mortality in the intensive care units. Despite increased knowledge about the pathophysiology underlying the clinical symptoms mortality remains high and has not decreased substantially over the last decades. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treating anemia Inventor(s): Creasy, Caretha; (Erdenheim, PA), Dillon, Susan B.; (Chester Springs, PA), Lord, Kenneth A.; (Collegeville, PA) Correspondence: Ratner & Prestia; P.O. Box 980; Valley Forge; PA; 19482-0980; US Patent Application Number: 20030176375 Date filed: May 14, 2001 Abstract: hYAK3-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK3-2 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers including testicular cancer; anorexia; bulimia; neutropenia; cytopenia; anemias, including anemias due to renal insufficiency or to chronic disease, such as autoimmunity or cancer, and drug-induced anemias; polycythemia; myelosuppression; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome., among others, and diagnostic assays for such conditions. Excerpt(s): This application claims priority to U.S. Ser. No. 60/118,045 filed Feb. 1, 1999, which is incorporated by reference in its entirety. This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to a serine/threonine protein kinase, hereinafter referred to as hYAK3-2. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. A number of polypeptide growth factors and hormones mediate their cellular effects through a signal transduction pathway. Transduction of signals from the cell surface receptors for these ligands to intracellular effectors frequently involves phosphorylation or dephosphorylation of specific protein substrates by regulatory protein serine/threonine kinases (PSTK) and phosphatases. Serine/threonine phosphorylation is a major mediator of signal transduction in multicellular organisms. Receptor-bound, membranebound and intracellular PSTKs regulate cell proliferation, cell differentiation and signalling processes in many cell types.
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Method to treat chronic heart failure and/or elevated cholesterol levels Inventor(s): Morkin, Eugene; (Tucson, AZ) Correspondence: Norman P. Soloway; Hayes Soloway P.C.; 130 W. Cushing Street; Tucson; AZ; 85701; US Patent Application Number: 20030147815 Date filed: February 18, 2003 Abstract: A method for treating a patient having congestive heart failure by administering a therapeutically effective amount of 3',3,5-triiodothyropropionic acid (TRIPROP) or 3,5,3',5'-tetraiodothyropr- opionic acid (TETRAPROP). Also described is a method to lower cholesterol blood levels of a patient by administering a therapeutically effective amounts of TRIPROP or TETRAPROP. Excerpt(s): This application is a Continuation-in-Part of co-pending U.S. application Ser. No. 09/774,994, filed Jan. 31, 2001. The present invention relates to a treatment for patients having congestive heart failure and/or elevated cholesterol blood levels. Congestive heart failure continues to be a major health problem, affecting about 4.6 million people in the United States, and its prevalence is predicted to increase over the next several decades. The magnitude of heart failure as a clinical problem has placed emphasis on the need to develop new treatment strategies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for treatment of disorders of cardiac contractility Inventor(s): Marban, Eduardo; (Lutherville, MD) Correspondence: Peter F. Corless; Dike, Bronstein, Roberts & Cushman, Llp; 130 Water Street; Boston; MA; 02109; US Patent Application Number: 20030186998 Date filed: April 1, 2003 Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 60/064,942, filed Nov. 7, 1997, which is incorporated herein by reference in its entiretv. The present invention relates to methods for modulating calcium sensitivity of cardiac muscle. In preferred aspects, the invention provides methods for enhancing myocardial contractility and cardiac performance, and methods for treatment of heart failure and other disorders associated with cardiac contractility bv administration of one or more compounds that can increase cardiac contractility such as a xanthine oxidase inhibitor compound. The invention also provides methods for increasing cardiac contraction efficiency through administration of a xanthine oxidase inhibitor. Heart failure afflicts more than two million Americans, and congestive heart failure is recognized as the most common cause of hospitalization and mortality in Western society. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods of treating heart failure with modified ATP, ADP and AMP compounds Inventor(s): Jacobson, Kenneth A.; (Silver Spring, MD), Liang, Bruce T.; (Marion Station, PA) Correspondence: Woodcock Washburn Llp; One Liberty Place, 46th Floor; 1650 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20030186929 Date filed: March 25, 2003 Abstract: Methods are provided for treating heart failure, increasing cardiac muscle contractility, increasing cardiac diastolic relaxation, and increasing vasodilation employing AMP, ADP, and ATP analogues. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 08/875,050, filed Sep. 23, 1997, which is a national phase application of PCT/US/96/03911, filed Mar. 22, 1996, which is a continuation-in-part of U.S. application Ser. No. 08/409,350, filed Mar. 23, 1995. The contents of the foregoing patent applications are incorporated herein by reference. This invention relates to methods for treating heart failure, to methods for increasing cardiac muscle contractility, to methods for increasing cardiac muscle diastolic relaxation, to methods for increasing cellular contraction and to methods for increasing vasodilation. Positive inotropic agents (i.e., agents which increase the contractility of cardiac muscle in a dose dependent manner) find use, inter alia, in the treatment of congestive heart failure and as vasodialators. Representative of the three classes of positive inotropic agents are the Na.sup.+/K.sup.+ ATPase inhibitor digitalis, the.beta.-adrenergic agonists dobutamine and dopamine, and the phosphodiesterase inhibitor amrinone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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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
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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 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 •
Novel compounds for treatment of cardiac arrhythmia, synthesis, and methods of use Inventor(s): Druzgala, Pascal; (Santa Rosa, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030158194 Date filed: December 10, 2002 Abstract: The subject invention pertains to novel compounds (and salts thereof), and compositions comprising the compounds, for the treatment of cardiac arrhythmias. The subject invention further concerns methods of making the novel compounds. The novel compounds are rapidly metabolized analogs of amiodarone, having the distinct and advantageous characteristic of being metabolized to a less lipophilic compound. This results in an improved safety profile. The new compounds have particular utility for treating life-threatening ventricular tachyarrhythmias, especially in patients with congestive heart failure (CHF). The compounds also provide effective management for
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ventricular arrhythmias and supraventricular arrhythmias, including atrial fibrillation and re-entrant tachyarrhythmias involving accessory pathways. Excerpt(s): This application claims the benefit of provisional patent application Serial No. 60/339,898, filed Dec. 10, 2001, which is hereby incorporated by reference in its entirety. Congestive heart failure (CHF) is a disease affecting approximately 2% of the population of the United States (Sami, M. H. [1991] J. Clin. Pharmacol. 31:1081). Despite advances in the diagnosis and treatment of CHF, the prognosis remains poor with a 5year mortality rate higher than 50% from the time of diagnosis (McFate Smith, W. [1985] Am. J. Cardiol. 55:3A; McKee, P. A., W. P. Castelli, P. M. McNamara, W. B. Kannel [1971] N. Engl. J. Med. 285:1441). In patients with CHF, the rate of survival is lowest in those patients with severe depression of left ventricular function and patients who have frequent ventricular arrhythmias. Patients with ventricular arrhythmias and ischemic cardiomyopathy have an increased risk of sudden death. The presence of ventricular tachycardia in patients with severe CHF results in a three-fold increase in sudden death compared to those without tachycardia (Bigger, J. T., Jr. [1987] Circulation 75 (Supplement IV):28). Because of the high prevalence of sudden unexpected death in patients with CHF, there has been a growing interest in the prognostic significance of arrhythmias in these patients. Several compounds have been used in the management of cardiac arrhythmias in patients with congestive heart failure. Unfortunately, antiarrhythmic drug therapy has been disappointing. The efficacy of anti-arrhythmic drugs markedly decreases as left ventricular function declines, such that only a small fraction of patients with CHF are responsive to anti-arrhythmic therapy. No anti-arrhythmic drug has prevented sudden death in patients with CHF. There is even a question of increased mortality associated with certain anti-arrhythmic drugs (the CAST investigators [1989] N. Engl. J. Med. 321:406). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel indazole peptidomimetics as thrombin receptor antagonists Inventor(s): Maryanoff, Bruce E.; (Forest Grove, PA), Pandey, Anjali; (Fremont, CA), Scarborough, Robert M.; (Half Moon Bay, CA), Zhang, Han-Cheng; (Lansdale, PA) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030199455 Date filed: March 31, 2003 Abstract: The invention is directed to novel indazole peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted indazole peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed. Excerpt(s): This invention relates to certain novel thrombin receptor antagonists, their synthesis and their use for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Thrombin is an important serine protease in hemostasis and thrombosis. One of the key actions of thrombin is cellular modulation via receptor
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activation. A functional human thrombin receptor (PAR-1), cloned by Coughlin in 1991 (T. -K. Vu, Cell 1991, 64, 1057), was found to be a member of the G-protein coupled receptor (GPCR) superfamily. The receptor activation putatively occurs by N-terminal recognition and proteolytic cleavage at the Arg-41/Ser42 peptide bond to reveal a truncated N-terminus. This new receptor sequence, which has an SFLLRN (Ser-Phe-LeuLeu-Arg-Asn) N-terminus acting as a tethered ligand to recognize a site on the receptor, can trigger activation and signal transduction leading to platelet aggregation. Since 1991, three other protease-activated receptors with extensive homology to the thrombin receptor, "PAR-2" (S. Nystedt, Proc. Natl. Acad. Sci USA 1994, 91, 9208), "PAR-3" (H. Ishihara, Nature 1997, 386, 502), and "PAR4" (W. -F. Xu, Proc. Natl. Acad. Sci USA 1998, 95, 6642), have been cloned. Thrombin receptor (PAR-1) specific antibody-induced blockade of the platelet thrombin receptor has shown efficacy against arterial thrombosis in vivo (J. J. Cook Circulation 1995, 91, 2961). Hence, antagonists of the thrombin receptor (PAR-1) are useful to block these protease-activated receptors and, as such, may be used to treat platelet mediated thrombotic disorders such as myocardial infarction, stroke, restenosis, angina, atherosclerosis, and ischemic conditions. The thrombin receptor (PAR-1) has also been identified on other cell types: endothelial, fibroblast, renal, osteosarcoma, smooth muscle, myocytes, tumor, and neuronal/glia. Thrombin activation of endothelial cells upregulates P-selectin to induce polymorphonuclear leukocyte adhesion--an inflammatory response of the vessel wall (Y. Sugama, J. Cell Biol. 1992, 119, 935). In fibroblasts, thrombin receptor (PAR-1) activation induces proliferation and transmission of mitogenic signals (D. T. Hung, J. Cell Biol. 1992, 116, 827). Thrombin has been implicated in osteoblast proliferation through its activation of osteoblast cells (D. N. Tatakis, Biochem. Biophys. Res. Commun. 1991, 174, 181). Thrombin has been implicated in the regulation and retraction of neurons (K. Jalink, J. Cell. Biol. 1992, 118, 411). Therefore, in this context, the antagonist compounds of this invention may also be useful against inflammation, osteoporosis, Angiogenesis related disorders, cancer, neurodegenerative disorders, hypertension, heart failure, arrhythmia, glomerulonephritis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pacing method and apparatus Inventor(s): Laske, Timothy G.; (Shoreview, MN), Williams, Terrell M.; (Brooklyn Park, MN) Correspondence: Medtronic, INC.; 710 Medtronic Parkway NE; Ms-lc340; Minneapolis; MN; 55432-5604; US Patent Application Number: 20030204233 Date filed: April 29, 2002 Abstract: The present invention provides for a method and apparatus providing pacing to improve the hemodynamics of the heart for patients with AV nodal block, right/left bundle branch block, and heart failure. A lead body having at least one conductor with an insulative sleeve is introduced into the right atrium of a heart. A partially masked helical electrode connected to the conductor is then secured preferably into the atrial aspect of the atrioventricular septum. The electrical conductor is then rotated such that an unmasked portion of the electrode is moved to a depth within the heart tissue substantially near the heart's intrinsic conduction system. This method and apparatus allow pacing in a natural manner via low power stimulation of the heart's intrinsic conduction system.
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Excerpt(s): The present invention generally relates to the field of implantable medical devices, and more particularly to a medical electrical lead providing improved pacing capabilities. Various types of pacing leads have been developed for endocardial introduction into different chambers of a patient's heart, typically the right ventricle or right atrial appendage, as well as the coronary sinus. These flexible leads usually are constructed having an outer polymeric sheath encasing one or more electrical conductors. One conductor is typically attached at its distal end to the shank portion of a tip electrode. In bipolar or multipolar leads, one or more further conductors are provided in coaxial or co-linear relation to the first conductor and are connected at their distal end to a more proximally located, ring-shaped electrode situated along the lead body. The proximal ends of each conductor are each coupled to a connector, which includes a single pin in unipolar leads, and additional pins or in-line rings in bipolar and multipolar leads. These pacing leads can be attached to a variety of pacing devices such as a single chamber atrial pacemaker (AAI), a single chamber ventricular pacemaker (VVI), or a dual chamber pacemaker (DDD). In a conventional AAI or VVI pacemaker, only one lead is required. Stimulation in the AAI pacemakers is normally performed with the lead located in the right atrium. Stimulation with a VVI pacemaker normally takes place in the apex of the right ventricle. The conventional DDD pacemaker requires two leads. Similar to AAI pacing, one of the DDD pacemaker leads is placed in the heart's right atrium and similar to VVI pacing another DDD pacemaker lead is placed in the apex of the right ventricle. The leads are used to sense electrical activity in the heart and to deliver stimulation pulses when spontaneous electrical activity ceases. The leads are often shaped so the atrial lead and the ventricular lead are adapted to conform to their desired placement in the heart when the electrode system is implanted. In a DDD lead system, the implantation of dual curved leads has proven difficult due to the complicated nature of implanting two curved leads into two separate chambers of the heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical composition comprising a sodium hydrogen exchange inhibitor and an angiotensin converting enzyme inhibitor Inventor(s): Linz, Wolfgang; (Mainz, DE), Schindler, Ursula; (Bad Soden, DE) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206; Mail Code: D303a; Bridgewater; NJ; 08807; US Patent Application Number: 20030158247 Date filed: February 4, 2003 Abstract: This invention is directed to a pharmaceutical composition comprising the sodium-hydrogen exchanger (NHE) inhibitor cariporide and an angiotensin converting enzyme (ACE) inhibitor which exhibits unexpectedly efficacious properties for preventing heart failure and other age-related organ dysfunctions, age-related disorders and for prolonging life, and to methods of preventing heart failure and other agerelated organ dysfunctions, age-related disorders and for prolonging life comprising administering pharmaceutically effective amounts of the sodium-hydrogen exchange inhibitor cariporide and an ACE inhibitor. Excerpt(s): This application is entitled to the benefit of earlier filed applications U.S. Application No. 60/362,051, filed Mar. 5, 2002, and Federal Republic of Germany Application Number 102 04 571.2, filed Feb. 4, 2002. The invention is directed to a pharmaceutical composition comprising a combination of cariporide, an inhibitor of the
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cellular sodium-hydrogen exchanger, and the ACE inhibitor ramipril, and to the use thereof in human and veterinary medicine for preventing heart failure and other agerelated functional disturbances and dysfunctional changes in organs of the body and for preventing age-related disorders and for prolonging life while preserving an improved quality of life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Phosphoinositide 3-kinase mediated inhibition of GPCRs Inventor(s): Barak, Larry S.; (Durham, NC), Caron, Marc G.; (Hillsborough, NC), Laporte, Stephane A.; (Outremont, CA), Naga Prasad, Sathyamangla V.; (Durham, NC), Rockman, Howard A.; (Chapel Hill, NC) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030182669 Date filed: March 19, 2002 Excerpt(s): The present invention relates to compounds that alter GPCR internalization and new methods for their identification. Compounds of this invention include modified phosphoinositide 3-kinase (PI3K), modified HEAT domain, modified.beta.adrenergic receptor kinase 1 (.beta.ARK1), as well as other peptides or small molecules that alter GPCR internalization. The present invention also includes the use of such compounds to treat GPCR-related diseases, such as cardiovascular disease, heart failure, asthma, nephrogenic diabetes insipidus, or hypertension. G protein-coupled receptors (GPCRs) are cell surface proteins that translate hormone or ligand binding into intracellular signals. GPCRs are found in all animals, insects, and plants. GPCR signaling plays a pivotal role in regulating various physiological functions including phototransduction, olfaction, neurotransmission, vascular tone, cardiac output, digestion, pain, and fluid and electrolyte balance. Although they are involved in various physiological functions, GPCRs share a number of common structural features. They contain seven membrane domains bridged by alternating intracellular and extracellular loops and an intracellular carboxyl-terminal tail of variable length. The magnitude of the physiological responses controlled by GPCRs is linked to the balance between GPCR signaling and signal termination. The signaling of GPCRs is controlled by a family of intracellular proteins called arresting. Arrestins bind activated GPCRs, including those that have been agonist-activated and especially those that have been phosphorylated by G protein-coupled receptor kinases (GRKs). These processes are affected by other molecules such as phosphatidylinositol 3,4,5-triphosphate (Ptdlns (3,4,5) P.sub.3), the main product catalyzed by the lipid kinase activity of phosphoinositide 3-kinase (PI3K). 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 •
Pyridazinyl phenyl hydrazones useful against congestive heart failure Inventor(s): Backstrom, Reijo; (Helsinki, FI), Haikala, Heimo; (Espoo, FI), Kaheinen, Petri; (Helsinki, FI), Kaivola, Juha; (Helsinki, FI), Levijoki, Jouko; (Helsinki, FI), Lonnberg, Kari; (Turku, FI), Luiro, Anne; (Helsinki, FI), Nore, Pentii; (Helsinki, FI), Pippuri, Aino; (Espoo, FI), Pystynen, Jarmo; (Espoo, FI) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030158200 Date filed: December 26, 2002
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Abstract: Therapeutically active compounds of formula (I) in which R.sub.1 to R.sub.4 means hydrogen, alkyl, alkenyl, aryl, arylalkyl, carboxyalkyl, hydroxyalkyl or halogenalkyl, or R.sub.2 and R.sub.3 form a ring of 5-7 carbon atoms. R.sub.5 to R.sub.9 means hydrogen, alkyl, alkenyl, aryl, arylalkyl, acyl, hydroxy, alkoxy, alkoxycarbonyl, amino, acylamino, alkylamino, aryloxy, halogen, cyano, nitro, carboxy, alkylsulfonyl, sulfonamido or trifluoromethyl, wherein each aryl residue defined above by itself or as a part of another group may be substituted, and pharmaceutically acceptable salts and esters thereof. The compounds increase the calcium sensitivity of contractile proteins of the cardiac muscle and are thus useful in the treatment of congestive heart failure. Excerpt(s): The present invention relates to pyridazinyl phenyl hydrazone compounds and pharmaceutically acceptable salts and esters thereof. The invention also relates to pharmaceutical compositions comprising such compounds as active ingredients. The compounds of the invention increase the calcium sensitivity of contractile proteins of the cardiac muscle and are thus useful in the treatment of congestive heart failure. Congestive heart failure is characterized by a decrease in cardiac output and an increase in right and left ventricular filling pressure. These hemodynamic conditions can produce symptoms of dyspnea, fatigue and edema. The contraction in cardiac muscle is triggered by the binding of calcium to contractile proteins. Series of phosphodiesterase isoenzyme III (PDE III) inhibitors are in clinical trials for the treatment of congestive heart failure. These compounds increase the contractility of the cardiac muscle and produce vasodilatation. However, it is known that the long-term application of those compounds may lead to calcium overload in the cardiac muscle and trigger arrhythmias. It is therefore desired to develop medicaments acting by a mechanism which would increase cardiac contractility without producing calcium overload. The increase of calcium sensitivity of contractile proteins would be such a mechanism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Regulation of human alpha 1A adrenergic receptor-line G protein-coupled receptor Inventor(s): Ramakrishnan, Shyam; (Brighton, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030187219 Date filed: May 5, 2003 Abstract: Reagents which regulate human.alpha.sub.1aadrenergic receptor-like GPCR and reagents which bind to human.alpha.sub.1a adrenergic receptor-like GPCR gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, infections such as bacterial, fungal, protozoan, and viral infections, particularly those caused by HIV viruses, pain, obesity cancers, anorexia, bulimia, asthma, Parkinson's diseases, acute heart failure, hypotension, hypertension, urinary retention, osteoporosis, angina pectoris, myocardial infarction, ulcers, asthma, allergies, multiple sclerosis, benign prostatic hypertrophy, and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, several mental retardation, and dyskinesias, such as Huntington's disease and Tourett's syndrome. Excerpt(s): The invention relates to the area of G-protein coupled receptors. More particularly, it relates to the area of human.alpha.sub.1a adrenergic receptor-like G protein-coupled receptors and their regulation. Many medically significant biological
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processes are mediated by signal transduction pathways that involve G-proteins (Lefkowitz, Nature 351, 353-354, 1991). The family of G-protein coupled receptors (GPCR) includes receptors for hormones, neurotransmitters, growth factors, and viruses. Specific examples of GPCRs include receptors for such diverse agents as dopamine, calcitonin, adrenergic hormones, endothelin, cAMP, adenosine, acetylcholine, serotonin, histamine, thrombin, kinin, follicle stimulating hormone, opsins, endothelial differentiation gene-1, rhodopsins, odorants, cytomegalovirus, Gproteins themselves, effector proteins such as phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins such as protein kinase A and protein kinase C. GPCRs possess seven conserved membrane-spanning domains connecting at least eight divergent hydrophilic loops. GPCRs (also known as 7TM receptors) have been characterized as including these seven conserved hydrophobic stretches of about 20 to 30 amino acids, connecting at least eight divergent hydrophilic loops. Most GPCRs have single conserved cysteine residues in each of the first two extracellular loops, which form disulfide bonds that are believed to stabilize functional protein structure. The seven transmembrane regions are designated as TM1, TM2, TM3, TM4, TM5, TM6, and TM7. TM3 has been implicated in signal transduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Regulation of human plc delta-1 Inventor(s): Xiao, Yonghong; (Cambridge, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030191060 Date filed: November 27, 2002 Abstract: Reagents which regulate human PLC delta-1 activity and reagents which bind to human PLC delta-1 gene products can be used, inter alia, to treat COPD, congestive heart failure, hypertension, and cancer, and a variety of conditions in which signal transduction is impaired. Excerpt(s): This application incorporates by reference co-pending application Serial No. 60/207,277 filed May 30, 2000. The invention relates to the regulation of human PLC delta-1 activity for therapeutic effects. Phospholipase C (PLC) belongs to a family of enzymes, also known as disulfide isomerases, which play a very important role in transmembrane signal transduction (see U.S. Pat. No. 5,587,306). Many extracellular signaling molecules including hormones, growth factors, neurotransmitters, and immunoglobulins bind to their respective cell surface receptors and activate PLCs. The role of an activated PLC is to catalyze the hydrolysis of phosphatidylinositol-4,5bisphosphate (PIP2), a minor component of the plasma membrane to produce diacylglycerol and inositol 1,4,5-trisphosphate (IP3). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Renal nerve stimulation method and apparatus for treatment of patients Inventor(s): Gelfand, Mark; (New York, NY), Levin, Howard R.; (Teaneck, NJ) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030216792 Date filed: April 8, 2003 Abstract: A method and apparatus for treatment of heart failure, hypertension and renal failure by stimulating the renal nerve. The goal of therapy is to reduce sympathetic activity of the renal nerve. Therapy is accomplished by at least partially blocking the nerve with drug infusion or electrostimulation. Apparatus can be permanently implanted or catheter based. Excerpt(s): This application is related and claims priority to the following commonlyowned provisional applications: Serial No. 60/370,190, entitled "Modulation Of Renal Nerve To Treat CHF", that was filed in the U.S. Patent and Trademark Office (USPTO) on Apr. 8, 2002; Serial No. 60/415,575 entitled "Modulation Of Renal Nerve To Treat CHF", that was filed in the USPTO on Oct. 3, 2002, and Serial No. 60/442,970 entitled "Treatment Of Renal Failure And Hypertension", that was filed in the USPTO on Jan. 29, 2003. The entirety of each of these provisional applications is incorporated by reference herein. This invention relates to methods and apparatus for treatment of congestive heart failure, chronic renal failure and hypertension by nerve stimulation. In particular, the invention relates to the improvement of these conditions of patients by blocking signals to the renal (kidney) nerve. Congestive Heart Failure (CHF) is a form of heart disease still increasing in frequency. According to the American Heart Association, CHF is the "Disease of the Next Millennium". The number of patients with CHF is expected to grow even more significantly as an increasing number of the "Baby Boomers" reach 50 years of age. CHF is a condition that occurs when the heart becomes damaged and reduces blood flow to the organs of the body. If blood flow decreases sufficiently, kidney function becomes impaired and results in fluid retention, abnormal hormone secretions and increased constriction of blood vessels. These results increase the workload of the heart and further decrease the capacity of the heart to pump blood through the kidney and circulatory system. This reduced capacity further reduces blood flow to the kidney, which in turn further reduces the capacity of the blood. It is believed that the progressively-decreasing perfusion of the kidney is the principal non-cardiac cause perpetuating the downward spiral of the "Vicious Cycle of CHF". Moreover, the fluid overload and associated clinical symptoms resulting from these physiologic changes are predominant causes for excessive hospital admissions, terrible quality of life and overwhelming costs to the health care system due to CHF. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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System for treating tissue swelling Inventor(s): Odland, Rick Mathew; (Roseville, MN) Correspondence: Philip M. Goldman; Fredrikson & Byron, P.A.; 4000 Pillsbury Center; 200 South Sixth Street; Minneapolis; MN; 55402-1425; US Patent Application Number: 20030187367 Date filed: October 17, 2002
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Abstract: A system and related methods and components for treating tissue swelling, and particularly swelling associated with cerebral edema, compartment syndrome, and congestive heart failure, by the use of water removal therapy, in order to remove only water from biological fluids. Included also is a system for such use that incorporates one or more monitors, optionally in addition to the use of water removal therapy. By removing only water, all other biologic agents, including essentially all solutes and formed blood elements (such as cells) are increased in concentration in the remaining bodily fluid(s). WRT can be applied to several clinical conditions in which there is an excess of water, and is ideally used in an extracorporeal fashion, in combination with other functions and related components as well, including ultrafiltration. Excerpt(s): The present application is a continuation-in-part of US patent application filed Mar. 22, 2002 and assigned Ser. No. 10/104,113, the entire disclosure of which is incorporated herein by reference. The present invention relates to methods and apparatuses for use in treating tissue swelling, including cerebral edema, compartment syndrome and congestive heart failure. In another aspect, the invention relates to diagnostic and therapeutic methods and apparatuses that include the placement of semipermeable catheters and membranes within the body. In yet another aspect, the invention relates to diagnostic and therapeutic methods and apparatuses adapted to monitor various physiologic parameters in the course of tissue swelling, as well as methods and apparatuses adapted to deliver media, including gases and liquids, to catheters positioned within a tissue, including to treat biological (e.g., bodily) fluids external to the body. In a final aspect, the invention relates to systems, and components thereof, for recovering fluids from sites of tissue swelling. A number of clinical conditions involve (e.g., are caused by and/or themselves cause) impaired circulation, and particularly circulation within interstitial spaces and within discrete, localized tissues. Among the more vexing examples of such circulatory afflictions are those that involve localized tissue swelling, including compartment syndrome and edema (and in particular, cerebral edema). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Thrombin receptor antagonists Inventor(s): Chackalamannil, Samuel; (East Brunswick, NJ), Chelliah, Mariappan V.; (Edison, NJ), Clasby, Martin C.; (Plainsboro, NJ), Xia, Yan; (Edison, NJ) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20030203927 Date filed: October 16, 2002 Abstract: Heterocyclic-substituted tricyclics of the formula 1or a pharmaceutically acceptable salts thereof, wherein:n.sub.1 and n.sub.2 are independently 0-2;Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group;B is alkyl or optionally substituted alkenyl;R.sup.22 is --COR.sup.23 or a carboxy, sulfinyl, sulfonyl, sulfonamide or amino acid derivative;R.sup.23 is haloalkyl; alkenyl; haloalkenyl; alkynyl; optionally substituted cycloalkyl; cycloalkyl-alkyl; aryl; arylalkyl; heteroaryl; heterocycloalkyl; or --COOH and/or --SO.sub.3H substituted alkyl;R.sup.1, R.sup.2, R.sup.3, R.sup.9, R.sup.10 and R.sup.11 are as defined in the specification;are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/330,359, filed Oct. 18, 2001. Thrombin is known to have a variety of activities in different cell types and thrombin receptors are known to be present in such cell types as human platelets, vascular smooth muscle cells, endothelial cells and fibroblasts. It is therefore expected that thrombin receptor antagonists will be useful in the treatment of thrombotic, inflammatory, atherosclerotic and fibroproliferative disorders, as well as other disorders in which thrombin and its receptor play a pathological role. Thrombin receptor antagonist peptides have been identified based on structure-activity studies involving substitutions of amino acids on thrombin receptors. In Bernatowicz et al, J. Med. Chem., 39 (1996), p. 4879-4887, tetra- and pentapeptides are disclosed as being potent thrombin receptor antagonists, for example N-trans-cinnamoyl-p-fluoroPhe-- pguanidinoPhe-Leu-Arg-NH.sub.2 and N-trans-cinnamoyl-p-fluoroPhe-p-guanidinoPhe-Leu-Arg-Arg-NH.sub.2. Peptide thrombin receptor anatgonists are also disclosed in WO 94/03479, published Feb. 17, 1994. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of fibrates for the preparation of a medicament useful in the treatment of congestive heart failure Inventor(s): Arduini, Arduino; (Rome, IT) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030176499 Date filed: May 8, 2003 Abstract: The use of fibrates, particularly clofibrate, is described for the preparation of a medicament useful in the treatment of congestive heart failure, and particularly the states of heart failure unrelated to dyslipidaemic conditions. Excerpt(s): The invention described herein relates to medicaments useful for the treatment of cardiovascular diseases, particularly congestive heart failure. Congestive heart failure (CHF) is an important cause of disability and sudden death (approximately 10%/year), with a high incidence (1-5 cases per 1,000 inhabitants in the younger age brackets; more than 30 cases per 1,000 inhabitants in patients aged above 75 years. The physiopathological mechanisms involved in the onset, development and progression of CHF have still to be fully clarified. Despite the fact that numerous biochemical, electrophysiological and functional abnormalities have been found, it is hard to establish whether these constitute a cause or a consequence of the disease. 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 heart failure, 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 “heart failure” (or synonyms) into
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the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on heart failure. You can also use this procedure to view pending patent applications concerning heart failure. 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 HEART FAILURE Overview This chapter provides bibliographic book references relating to heart failure. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on heart failure 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 “heart failure” (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 heart failure: •
Dental Management of the Medically Compromised Patient. 5th ed Source: St. Louis, MO: Mosby, Inc. 1997. 668 p. Contact: Available from Harcourt Health Sciences. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 325-4177. Fax (800) 874-6418. Website: www.harcourthealth.com. PRICE: $48.00 plus shipping and handling. ISBN: 0815156340. Summary: A working knowledge of the multitude of compromised health states is essential for dental professionals, as the majority of medically compromised patients need or want oral health care. This knowledge will support high standards for dental and oral health care delivery, which include recognizing and understanding conditions that reflect compromised states, preventing adverse side effects of procedures and drugs used in dentistry, and formulating treatment plans that are consistent with a patient's medical status. This text offers 28 chapters that provide the dental practitioner with an up to date reference work describing the dental management of patients with selected
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medical problems. After an introductory chapter on the interrelationships between medicine and dentistry, the text covers infective endocarditis, rheumatic fever and rheumatic heart disease, congenital heart disease, surgically corrected cardiac and vascular disease, hypertension, ischemic heart disease, cardiac arrhythmias, congestive heart failure, pulmonary disease, chronic renal failure and dialysis, liver disease, gastrointestinal disease, sexually transmitted diseases, AIDS and related conditions, arthritis, neurologic disorders, diabetes, adrenal insufficiency, thyroid disease, pregnancy and breastfeeding, allergy, bleeding disorders, blood dyscrasias, oral cancer, behavioral and psychiatric disorders, organ transplantation, and prosthetic implants. Two appendices offer an overview of infection control and a review of the therapeutic management of common oral lesions. Each chapter includes black and white photographs and concludes with references. A subject index concludes the volume. •
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 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).
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Medical Emergencies in the Dental Office. 5th ed Source: St. Louis, MO: Mosby, Inc. 2000. 540 p. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. E-mail:
[email protected]. Website: www.mosby.com. PRICE: $52.95 plus shipping and handling. ISBN: 1556644205. Summary: Maintaining a high level of skill in the prevention, recognition, and management of medical emergencies is important in the field of dentistry. This textbook covers the management of medical emergencies in the dental office. Thirty chapters are offered in eight sections: prevention, unconsciousness, respiratory distress, altered consciousness, seizures, drug related emergencies, chest pain, and cardiac arrest. Specific topics include medicolegal considerations, vasodepressor syncope (fainting), postural hypotension (low blood pressure and feeling faint upon getting up from a prone or semi prone position), acute adrenal insufficiency, differential diagnosis, airway obstruction, hyperventilation, asthma, heart failure, acute pulmonary edema (fluid in the lungs), diabetes mellitus, thyroid gland dysfunction, cerebrovascular accident (stroke), drug overdose reactions, allergy, angina pectoris, acute myocardial infarction, and cardiac arrest and cardiopulmonary resuscitation. The text concludes with a quick
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reference section to life threatening situations (offered in algorithm format) and a subject index. Each chapter includes black and white photographs and extensive references. •
Regulation of Sodium and Chloride Balance Source: New York, NY: Raven Press. 1990. 540 p. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 869-3495. PRICE: $72.50 plus shipping. ISBN: 0881674818. Summary: This book discusses the regulation of sodium and chloride balance in eighteen chapters divided into two sections: normal sodium and chloride balance and abnormal sodium and chloride balance. Topics covered include the distribution of sodium chloride across cell membranes, the regulation of sodium chloride distribution within the extracellular space, mechanisms of segmental sodium and chloride reabsorption, glomerulotubular balance and the regulation of sodium excretion by intrarenal hemodynamics, the integrated regulation of electolyte balance and blood pressure by the renin system, the renin system and its pathophysiology in disease, the diagnosis of sodium and chloride disturbances, sodium blance and fluid volume in normal and edematous states, the edema of congestive heart failure, the pathogenesis of edema in the nephrotic syndrome, the edema of cirrhosis and its treatment, idopathic edema of women and its treatment, salt wastage and salt depletion, the diagnosis and treatment of hyponatremia, sodium handling in hypertensive states, the primary and seconary effects of diuretics, and the applied pharmcokinetics and drug resistance of diretics. A subject index concludes the volume.
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Mayo Clinic on High Blood Pressure Source: New York, NY: Kensington Publishing. 1999. 180 p. Contact: Available from Mayo Clinic. 200 First Street, S.W., Rochester, MN 55905. (800) 291-1128 or (507) 284-2511. Fax (507) 284-0161. Website: www.mayo.edu. PRICE: $14.95 plus shipping and handling. ISBN: 1893005011. Summary: This book focuses on what people who have high blood pressure can do to better manage their blood pressure and keep it at a safe level. The book begins with a chapter that explains the basics of blood pressure, how high blood pressure develops, and why it can be harmful. This is followed by a chapter that identifies unmodifiable and modifiable risk factors for high blood pressure. Unmodifiable risk factors include race, age, family history, and gender. Modifiable risk factors include obesity, inactivity, tobacco use, sodium sensitivity, low potassium, excessive alcohol consumption, stress, chronic illness, high cholesterol, diabetes, sleep apnea, and heart failure. Other topics addressed in this chapter include secondary high blood pressure and ways of preventing high blood pressure. The third chapter focuses on the diagnosis and treatment of high blood pressure. Topics include measuring blood pressure, receiving a diagnosis, getting a medical evaluation, and deciding on treatment with either medication or lifestyle changes. Subsequent chapters discuss determining a healthy weight, losing weight, becoming more physically active, and eating well using the Dietary Approaches to Stop Hypertension (DASH) plan. The following chapters detail the effects of sodium, tobacco, alcohol, caffeine, and stress on blood pressure. Another chapter focuses on the mode of action and side effects of various medications used in controlling high blood pressure, including diuretics, beta blockers, angiotensinconverting enzyme inhibitors, angiotensin II receptor blockers, calcium antagonists, alpha blockers, central acting agents, and direct vasodilators. Remaining chapters
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examine factors unique to women, management of high blood pressure among specific populations and groups, treatment of difficult-to-control high blood pressure, management of a hypertensive emergency, and home monitoring of blood pressure. The book also includes a week of menus based on the recommendations of the DASH eating plan. 17 figures. 2 tables. •
Coronary artery disease in women: What all physicians need to know Source: Philadelphia, PA: American College of Physicians: American Society of Internal Medicine. 1999. 615 pp. Contact: Available from American College of Physicians-American Society of Internal Medicine, 190 North Independence Mall West, Philadelphia, PA 19106. Telephone: (215) 351-2400 or (800) 523-1546 / fax: (215) 351- 2799 / e-mail:
[email protected] / Web site: http://www.acponline.org. $43 for nonmembers, $32 for members; plus shipping and handling. Summary: This book for health care practitioners reviews all important aspects of coronary artery disease, with an emphasis on gender differences, age, and race. It contains five parts: the introduction, prevention, diagnosis, management, and conclusion. The section on prevention discusses smoking; diabetes and insulin resistance; the history and pharmacologic management of lipids/cholesterol; nutrition; hypertension; obesity; exercise as prevention; aspirin, antioxidants, and alcohol; and issues in hormone replacement therapy. The diagnosis section provides information on the differential diagnosis of chest pain, noninvasive testing techniques, and influence of gender in coronary angiography. Topics in the the section on management include angina pectoris, acute coronary syndromes, bypass grafting risks, angioplasty, congestive heart failure, psychosocial issues, and pharmacologic secondary prevention. The concluding section discusses future trends in treatment and research. Each chapter contains a summary and list of references. Numerous charts and graphs present statistical information. The book concludes with an index.
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Women's concise guide to a healthier heart Source: Cambridge, MA: Harvard University Press. 1997. 136 pp. Contact: Available from Harvard University Press, 79 Garden Street, Cambridge, MA 02138. Telephone: (800) 448-2242 or (617) 495-2600 / fax: (800) 962-4983. $12.95. Summary: This book for the general public focuses on recognizing and preventing heart diseases in women. It is divided into three parts. Part one defines the most common heart diseases such as angina pectoris, arrhythmia, coronary artery disease, heart failure, and heart valve disorders. The second part elaborates on other conditions that impact the heart's function. Topics include diabetes, high blood pressure, high cholesterol, obesity, and stroke. Part three discusses various ways of preventing or controlling heart disease, such as alcohol use, diet, estrogen replacement therapy, exercise, quitting smoking, stress reduction, and weight control. The book concludes with a resource listing and an index.
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Dental Management of the Medically Compromised Patient. 4th ed Source: St. Louis, MO: Mosby-Year Book, Inc. 1993. 605 p. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 432-
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1380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $39.95 plus shipping and handling. ISBN: 0801668379. Summary: This book was written to provide the dental practitioner with an up-to-date, concise reference work describing the dental management of patients with selected medical problems. Twenty-seven chapters cover the interrelationships of medicine and dentistry; infective endocarditis; rheumatic fever, rheumatic heart disease, and murmurs; congenital heart disease; surgically-corrected cardiac and vascular disease; hypertension; ischemic heart disease; cardiac arrhythmias; congestive heart failure; pulmonary disease; chronic renal failure and dialysis; liver disease; sexually transmitted diseases; AIDS and related conditions; arthritis; neurologic disorders; diabetes; adrenal insufficiency; thyroid disease; pregnancy and breast-feeding; allergy; bleeding disorders; blood dyscrasias; oral cancer; behavioral and psychiatric disorders; organ transplantation; and prosthetic implants. Where appropriate, medical problems are organized to provide a brief overview of the basic disease process, pathophysiology, signs and symptoms, laboratory findings, and currently accepted medical therapy for each disorder. This is followed by a detailed explanation and recommendations for specific dental management. Two appendices cover infection control and the therapeutic management of common oral lesions. A detailed subject index concludes the text. •
Handbook of Liver Disease Source: Philadelphia, PA: Churchill-Livingstone. 1998. 534 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. Email:
[email protected]. PRICE: $73.00 plus shipping and handling. ISBN: 0443055203. Summary: This comprehensive handbook in outline format offers easy access to information on the full range of liver disorders, and covers symptoms, signs, differential diagnoses, and treatments. A total of 34 chapters cover the following topics: assessment of liver function and diagnostic studies, acute liver failure, chronic viral hepatitis, acute viral hepatitis, autoimmune hepatitis, alcoholic liver disease, fatty liver and nonalcoholic steatohepatitis, drug induced and toxic liver disease, cirrhosis and portal hypertension, portal hypertension and gastrointestinal bleeding, ascites and spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic encephalopathy, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson's disease and related disorders, alpha 1 antitrypsin deficiency and other metabolic liver diseases, Budd Chiari syndrome and other vascular disorders, the liver in heart failure, the liver in pregnancy, the liver in systemic disease, pediatric liver disease, liver disease in the elderly, HIV and the liver, granulomatous liver disease, hepatic tumors, hepatic abscesses and cysts, other infections involving the liver, surgery in the patient with liver disease and postoperative jaundice, liver transplantation, cholelithiasis and cholecystitis, diseases of the bile ducts, and tumors of the biliary tract. The book features lists that summarize key information and numerous figures and tables on topics such as acetaminophen toxicity, classifications of chronic hepatitis, and indications for liver transplantation. Each chapter was written by an acknowledged expert in the field and includes references for additional study. A subject index concludes the volume.
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Primer on Kidney Diseases. 2nd ed Source: San Diego, CA: Academic Press. 1998. 542 p.
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Contact: Available from Academic Press. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 321-5068 or (407) 345-3800. Fax (800) 874-6418 or (407) 345-4060. E-mail:
[email protected]. Website: www.apnet.com. PRICE: $57.95 plus shipping and handling. ISBN: 0122990900. Summary: This comprehensive textbook on kidney diseases is designed for medical students, house staff, and practitioners. The text offers a summary of the management of renal disease and fluid and electrolyte disorders. The 79 chapters are categorized in 11 sections, covering renal function and its assessment, electrolyte disorders, glomerular disease, the kidney in systemic disease, acute renal failure, drugs and the kidney, hereditary renal diseases, tubulointerstitial diseases, the kidney in special circumstances, chronic renal disease, and hypertension. Specific chapter topics include the characteristics of kidney function in the very young and in the very old, tubulointerstitial diseases, analgesic abuse nephropathy and the effects of NSAIDs on the kidneys, hematuria (blood in the urine), proteinuria, renal imaging techniques, metabolic acidosis and alkalosis, edema and the clinical use of diuretics, immunopathogenesis, minimal change nephropathy, IgA nephropathy, Goodpasture's syndrome, renal function in congestive heart failure, renal function in liver disease, renal manifestations of systemic lupus erythematosus, diabetic nephropathy, dysproteinemias and amyloidosis, renal and urologic complications of cancer and its treatment, hemolytic uremic syndrome, the renal manifestations of HIV, interstitial nephritis, sickle cell nephropathy, Alport's syndrome, medullary cystic disease, tubulointerstitial disease, lead nephrotoxicity, lithium induced renal disease, medullary sponge kidney, obstructive uropathy, nephrolithiasis (kidney stones), urinary tract infections, the kidney in pregnancy, the uremic syndrome, hemodialysis and hemofiltration, peritoneal dialysis, nutrition and renal disease, renal osteodystrophy, renal transplantation, and the pathogenesis of hypertension. Each chapter is written by an established expert in the field. The book is illustrated with full color and black and white photographs, figures, and tables. Each chapter concludes with suggested readings. An extensive subject index concludes the text. •
Therapy for Diabetes Mellitus and Related Disorders. 3rd ed Source: Alexandria, VA: American Diabetes Association. 1998. 487 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 0945448945. Summary: This handbook focuses on the treatment of problems that are of importance in the management of people with diabetes mellitus. The book attempts to help health professionals apply major advances in health care to their patients. Topics include the diagnosis and classification of diabetes mellitus, genetic counseling for type 1 diabetes, gestational diabetes mellitus, the management of pregnant women who have diabetes, antepartum and intrapartum obstetric care, neonatal problems and their management, type 1 diabetes and diabetic ketoacidosis in children, psychosocial adjustment in children who have type 1 diabetes, psychosocial aspects in adults, diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic syndrome in adults, and lactic acidosis. Other topics include the role of diabetes education in patient management; self monitoring of blood glucose; the rationale for management of hyperglycemia; medical nutrition therapy; pharmacological treatment of obesity; exercise; oral hypoglycemic agents such as sulfonylureas, repaglinide, metformin, alpha glucosidase inhibitors, and thiazolidinediones; insulin treatment; insulin pump therapy; combination therapy for
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hyperglycemia; and diabetes complications. In addition, the book discusses surgery and anesthesia in people with diabetes, geriatric patient care, hypoglycemia in patients who have type 1 diabetes, insulin allergy and insulin resistance, drugs and hormones that increase blood glucose levels, diabetic dyslipidemia, antihypertensive therapy, cutaneous disorders associated with diabetes mellitus, infections, visual loss, ocular complications, drug induced renal dysfunction, diabetic nephropathy, chronic kidney disease, painful or insensitive lower extremity, mononeuropathy and amyoradiculopathy, gastrointestinal disturbances, and bladder dysfunction. Final topics include erectile dysfunction, female sexual disorders, postural hypotension, sudomotor dysfunction and dark vision, cardiac denervation syndrome, noninvasive cardiac testing, angina and congestive heart failure, myocardial infarction, peripheral vascular disease, and foot ulcers and infections. The book includes an index. Numerous figures. Numerous tables. Numerous references. •
You Can Control Diabetes and High Blood Pressure: Self Care Handbook Source: South Deerfield, MA: Channing L. Bete Co., Inc. 2000. 31 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $2.73 each; plus shipping and handling; quantity discounts available. Summary: This handbook provides people who have diabetes with self care advice for managing high blood pressure. The handbook begins with an explanation of diabetes and high blood pressure and the complications they can cause. Having both conditions puts a person at greater risk of stroke, coronary artery disease, heart failure, kidney disease, blindness, reduced circulation to the feet and legs, and nerve damage. The handbook then provides guidelines for monitoring blood glucose and blood pressure, setting weight and exercise goals, making other lifestyle changes to improve health, eating balanced meals and snacks, and managing their medications. The handbook includes charts and worksheets that help readers with managing their diabetes and high blood pressure. The handbook also stresses the importance of undergoing regular screenings, caring for one's emotional health, and seeking outside assistance when needed. The handbook includes a list of organizations that can answer questions about diabetes and high blood pressure.
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Kidney Disease in Primary Care Source: Baltimore, MD: Williams and Wilkins. 1998. 297 p. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. E-mail:
[email protected]. PRICE: $39.95. ISBN: 0683300571. Summary: This textbook provides primary care physicians with practical approaches to common clinical problems of kidney diseases. Interpretation of common radiographic and laboratory techniques are discussed, as are approaches to fluid and electrolyte disturbances. The first seven chapters cover urinalysis and assessment of urinary electrolytes; radiologic studies of common renal diseases; nuclear imaging of the genitourinary system; evaluating renal function in acute and chronic renal failure; hyponatremia and hypernatremia (sodium); hypokalemia and hyperkalemia (potassium); and hypomagnesemia and hypermagnesemia (magnesium). The problem of patients presenting with elevated levels of urea and creatinine is discussed in depth, as are outpatient issues such as the proper approach to proteinuria and management strategies for hypertension, heart failure, edema, diabetes, glomerulonephritis,
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polycystic kidney disease, kidney stones, and urinary tract infections. In addition, the authors cover issues of patient counseling, proper drug dosing, and nutritional approaches. Kidney transplantation is not covered in depth; however, one chapter addresses the management of renal transplant patients. Each of the 24 chapters is written by nephrology experts and include an outline of content, specific diagnostic and management strategies, suggestions for when to refer a patient, and suggested readings. A subject index concludes the textbook. •
Diabetes and Cardiovascular Disease Source: Totowa, NJ: The Humana Press, Inc. 2001. 458 p. 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: With over ten million diagnosed patients and another five million undiagnosed, diabetes mellitus and its complications is a major public health problem that will assume epidemic proportions as the population grows older. This textbook offers practicing physicians the day to day practical knowledge about cardiovascular disease and diabetes. The 24 chapters in the book focus on either clinical or basic aspects of diabetes and cardiovascular disease. Part I, pathophysiology, reviews the mechanisms and risk factors for diabetic cardiovascular disease. Specific topics include the effects of insulin on the vascular system, vascular abnormalities in the prediabetic state, diabetes and advanced glycation end products, diabetes and hypertension (high blood pressure), the renin-angiotensin system, diabetes and dyslipidemia (disordered levels of fats in the blood), diabetes and thrombosis (blood clotting), diabetes and atherosclerosis (hardening and narrowing of the arteries), and nitric oxide and its role in diabetes mellitus. Part II focuses on the heart in diabetes mellitus, including coronary artery disease and congestive heart failure, including the preoperative assessment and perioperative management of the surgical patient with diabetes mellitus. Part III, the peripheral vascular system, addresses epidemiology (incidence and prevalence), mechanisms, methods of assessment, and treatment of this macrovascular disease. Specific topics include diabetes and arterial stiffness, methods for assessing large vessel pathophysiology, and peripheral vascular disease in patients with diabetes mellitus. And Part IV reviews the different microvascular effects in individuals with diabetes mellitus, including retinopathy (eye disease), nephropathy (kidney disease), neuropathy (nerve disease), and microcirculation of the diabetic foot. Each chapter includes extensive references and a subject index concludes the text.
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 “heart failure” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “heart failure” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “heart failure” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):
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20 Questions in Heart Failure by Robert J. Macfadyen (2003); ISBN: 1850092060; http://www.amazon.com/exec/obidos/ASIN/1850092060/icongroupinterna
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ABC of Heart Failure by Christopher R. Gibbs (Editor), et al; ISBN: 072791457X; http://www.amazon.com/exec/obidos/ASIN/072791457X/icongroupinterna
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Ace Inhibitors in Heart Failure: Advancing Clinical Practice (Journal - Cardiology , Vol 87, Suppl. 1) by M.K. Davies (Editor), T. Giles (Editor) (1996); ISBN: 3805562721; http://www.amazon.com/exec/obidos/ASIN/3805562721/icongroupinterna
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Acute and Chronic Heart Failure: Diagnosis and Therapy by Wulf-Dirk Bussmann (1986); ISBN: 0387159053; http://www.amazon.com/exec/obidos/ASIN/0387159053/icongroupinterna
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Acute Heart Failure (1989); ISBN: 3540191690; http://www.amazon.com/exec/obidos/ASIN/3540191690/icongroupinterna
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Acute Heart Failure (Update in Intensive Care and Emergency Medicine, 6) by J.L. Vincent (Editor), Claude Perret; ISBN: 0387191690; http://www.amazon.com/exec/obidos/ASIN/0387191690/icongroupinterna
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Acute Heart Failure in Intensive Care: A New Approach by P. Foex (Editor), I. A. Davidson (Editor) (1990); ISBN: 3805552556; http://www.amazon.com/exec/obidos/ASIN/3805552556/icongroupinterna
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An Atlas of Heart Failure by J. Cleland, et al; ISBN: 1850700419; http://www.amazon.com/exec/obidos/ASIN/1850700419/icongroupinterna
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An Illustrated Guide to Heart Failure by John G. F. Cleland, Robert J. Macfadyen (2002); ISBN: 1850091811; http://www.amazon.com/exec/obidos/ASIN/1850091811/icongroupinterna
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Arrhythmias in Heart Failure by William G. Stevenson (Editor), et al (2002); ISBN: 0879937076; http://www.amazon.com/exec/obidos/ASIN/0879937076/icongroupinterna
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Biochemistry of Hypertrophy and Heart Failure (Developments in Molecular and Cellular Biochemistry, 43) by Lorrie A. Kirshenbaum (Editor), et al (2003); ISBN: 1402074344; http://www.amazon.com/exec/obidos/ASIN/1402074344/icongroupinterna
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Cardiomyopathies and Heart Failure: Biomolecular, Infectious, and Immune Mechanisms (Developments in Cardiovascular Medicine, 248) by Akira, Md. Matsumori (Editor) (2003); ISBN: 1402074387; http://www.amazon.com/exec/obidos/ASIN/1402074387/icongroupinterna
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Characteristics of Contractile Dysfunction in Human Heart Failure by M. Miserez (1994); ISBN: 906186660X; http://www.amazon.com/exec/obidos/ASIN/906186660X/icongroupinterna
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Choose Health Over Heart Failure (Patient Workbook) by Michael E. McIvor; ISBN: 0072491833; http://www.amazon.com/exec/obidos/ASIN/0072491833/icongroupinterna
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Chronic Cardiac Disease: Optimizing Therapeutic Efficacy in Heart Failure by Simon Stewart (2002); ISBN: 186156290X; http://www.amazon.com/exec/obidos/ASIN/186156290X/icongroupinterna
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Chronic Heart Failure by M. Bohm, et al (1997); ISBN: 3540635793; http://www.amazon.com/exec/obidos/ASIN/3540635793/icongroupinterna
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Chronic Heart Failure: I Quality of Life. II Nitrate Therapy by H. Viefhues (Editor), et al; ISBN: 3540536779; http://www.amazon.com/exec/obidos/ASIN/3540536779/icongroupinterna
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Clinical Management of Heart Failure by James B. Young, Roger M. Mills; ISBN: 188473555X; http://www.amazon.com/exec/obidos/ASIN/188473555X/icongroupinterna
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Common Causes of Congestive Heart Failure (Humanatomy, 13) by Tim Peters (1995); ISBN: 1879874466; http://www.amazon.com/exec/obidos/ASIN/1879874466/icongroupinterna
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Congestive Heart Failure by Rose. Pinneo; ISBN: 0838511694; http://www.amazon.com/exec/obidos/ASIN/0838511694/icongroupinterna
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Congestive Heart Failure - Advances in Treatment and Their Market Potential [DOWNLOAD: PDF] by Drug and Market Development Publishing (Author); ISBN: B00005V7WR; http://www.amazon.com/exec/obidos/ASIN/B00005V7WR/icongroupinterna
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Congestive Heart Failure (Developments in Cardiovascular Medicine) by Joel Morganroth, E. Neil Moore (Editor) (1987); ISBN: 0898389550; http://www.amazon.com/exec/obidos/ASIN/0898389550/icongroupinterna
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Congestive Heart Failure Digest : Understanding this Growing Coronary Syndrome [DOWNLOAD: PDF]; ISBN: B00009KF1Z; http://www.amazon.com/exec/obidos/ASIN/B00009KF1Z/icongroupinterna
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Congestive Heart Failure Symposium: Prazosin in Ambulatory Patients With Heart Failure by D. Holmes (Editor) (1984); ISBN: 0199220034; http://www.amazon.com/exec/obidos/ASIN/0199220034/icongroupinterna
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Congestive Heart Failure: Current Research and Clinical Applications by Eugene Braunwald; ISBN: 0808914693; http://www.amazon.com/exec/obidos/ASIN/0808914693/icongroupinterna
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Congestive Heart Failure: Pathophysiology, Diagnosis and Treatment by Jon D. Blumenfeld, John H. Laragh (1994); ISBN: 0963240064; http://www.amazon.com/exec/obidos/ASIN/0963240064/icongroupinterna
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Congestive Heart Failure: Pathophysiology, Diagnosis, and Comprehensive Approach to Management by Jeffrey D. Hosenpud (Editor), et al; ISBN: 0683304372; http://www.amazon.com/exec/obidos/ASIN/0683304372/icongroupinterna
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Congestive Heart Failure: What You Should Know (Your Health: What You Should Know) by Dean, Dr Kereiakes, et al; ISBN: 1558705511; http://www.amazon.com/exec/obidos/ASIN/1558705511/icongroupinterna
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Congestive Heart Failure: Worldwide Drug and Medical Device Markets [DOWNLOAD: PDF] by Kalorama Information (Author); ISBN: B00006473U; http://www.amazon.com/exec/obidos/ASIN/B00006473U/icongroupinterna
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Contemporary Diagnosis and Management of Heart Failure by Barry H. Greenberg, Denise D. Hermann; ISBN: 1884065465; http://www.amazon.com/exec/obidos/ASIN/1884065465/icongroupinterna
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Current Chronic Heart Failure by W.S. Colucci, S.W. Davies (2002); ISBN: 1858733847; http://www.amazon.com/exec/obidos/ASIN/1858733847/icongroupinterna
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Death by Deception: Unmasking Heart Failure by Dick Quinn, et al (1996); ISBN: 0965334600; http://www.amazon.com/exec/obidos/ASIN/0965334600/icongroupinterna
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Device Therapy for Congestive Heart Failure by Kenneth A. Ellenbogen (Editor), et al (2003); ISBN: 0721602797; http://www.amazon.com/exec/obidos/ASIN/0721602797/icongroupinterna
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Diagnostic Reasoning Series: Heart Failure by Accredited by the AMA, Frank H. MD Netter (Illustrator); ISBN: 0914168452; http://www.amazon.com/exec/obidos/ASIN/0914168452/icongroupinterna
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Diuretics in Hypertension and in Heart Failure (Progress in Pharmacology and Clinical Pharmacology, Vol 10, No 3) by Ariel J. Reyes (Editor) (1995); ISBN: 3437116142; http://www.amazon.com/exec/obidos/ASIN/3437116142/icongroupinterna
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Drug Treatment of Heart Failure; ISBN: 0911741046; http://www.amazon.com/exec/obidos/ASIN/0911741046/icongroupinterna
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Drugs of Tomorrow: Chronic and Acute Heart Failure- Diverse Strategies for a Complex Disease [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B00008R3XA; http://www.amazon.com/exec/obidos/ASIN/B00008R3XA/icongroupinterna
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Exercise and Heart Failure by Gary J. Balady (Editor), Ileana L. Pina (Editor); ISBN: 0879936673; http://www.amazon.com/exec/obidos/ASIN/0879936673/icongroupinterna
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From Hypertension to Heart Failure by M. Bohm (Editor), et al (1998); ISBN: 3540635424; http://www.amazon.com/exec/obidos/ASIN/3540635424/icongroupinterna
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From Hypertension to Heart Failure by J.G.F. Cleland, J. McMurray (1995); ISBN: 1858730597; http://www.amazon.com/exec/obidos/ASIN/1858730597/icongroupinterna
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Heart Diseases and Disorders Sourcebook: Basic Consumer Health Information About Heart Attacks, Angina, Rhythm Disorders, Heart Failure, Valve Disease, Congenital Heart Disorders, and More by Karen Bellenir (Editor) (2000); ISBN: 0780802381; http://www.amazon.com/exec/obidos/ASIN/0780802381/icongroupinterna
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Heart Failure by Adam, MD Timmis (2003); ISBN: 0443074666; http://www.amazon.com/exec/obidos/ASIN/0443074666/icongroupinterna
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Heart Failure (1992); ISBN: 3540531459; http://www.amazon.com/exec/obidos/ASIN/3540531459/icongroupinterna
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Heart Failure by Ivy Goodman (1983); ISBN: 0877451192; http://www.amazon.com/exec/obidos/ASIN/0877451192/icongroupinterna
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Heart Failure by Horacio J., Md Adrogue, et al; ISBN: 0865424292; http://www.amazon.com/exec/obidos/ASIN/0865424292/icongroupinterna
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Heart Failure (Current Topics in Cardiology) by David McCall, Shahbudin H. Rahimtoola (Editor) (1995); ISBN: 0412044412; http://www.amazon.com/exec/obidos/ASIN/0412044412/icongroupinterna
242 Heart Failure
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Heart Failure (Pocket Picture Guides) by Adam D. Timmis, Simon W. Davies (1992); ISBN: 1563755807; http://www.amazon.com/exec/obidos/ASIN/1563755807/icongroupinterna
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Heart Failure and Arrhythmias by J. Brachmann, et al (1990); ISBN: 0387520414; http://www.amazon.com/exec/obidos/ASIN/0387520414/icongroupinterna
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Heart Failure and Arrhythmias (1990); ISBN: 3540520414; http://www.amazon.com/exec/obidos/ASIN/3540520414/icongroupinterna
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Heart Failure and Pulmonary Edema: Expert Drug Therapy Series (Expert Drug Therapy Series) by Blanchard, et al (2000); ISBN: 1930138083; http://www.amazon.com/exec/obidos/ASIN/1930138083/icongroupinterna
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Heart Failure Annual 2003 by Marc Brigham Pfeffer, et al; ISBN: 1841840726; http://www.amazon.com/exec/obidos/ASIN/1841840726/icongroupinterna
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Heart Failure in Practice (In Practice) by B. Chin, et al (2001); ISBN: 1853154873; http://www.amazon.com/exec/obidos/ASIN/1853154873/icongroupinterna
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Heart Failure Renin System by Gorlin (1998); ISBN: 0721619487; http://www.amazon.com/exec/obidos/ASIN/0721619487/icongroupinterna
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Heart Failure Today by L.H. Opie, F. Sabino (Editor) (1988); ISBN: 3805549296; http://www.amazon.com/exec/obidos/ASIN/3805549296/icongroupinterna
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Heart Failure: A Cirtical Inquiry in to American Medicine & the Revolution in Heart Care by Moore J.; ISBN: 0517081024; http://www.amazon.com/exec/obidos/ASIN/0517081024/icongroupinterna
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Heart Failure: A Clinician's Guide to Ambulatory Diagnosis and Treatment (Contemporary Cardiology) by Mariell L. Jessup (Editor), Evan Loh (Editor) (2003); ISBN: 1588290417; http://www.amazon.com/exec/obidos/ASIN/1588290417/icongroupinterna
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Heart Failure: A Critical Inquiry into American Medicine and the Revolution in Heart Care by Thomas J. Moore; ISBN: 039456958X; http://www.amazon.com/exec/obidos/ASIN/039456958X/icongroupinterna
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Heart Failure: A Guide for Patients by Denn (Illustrator), et al (1996); ISBN: 1885274408; http://www.amazon.com/exec/obidos/ASIN/1885274408/icongroupinterna
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Heart Failure: An Incredibly Easy! Miniguide by Springhouse Corporation, Michael Shaw; ISBN: 1582550115; http://www.amazon.com/exec/obidos/ASIN/1582550115/icongroupinterna
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Heart Failure: Basic Science and Clinical Aspects by Judith K. Gwathmey, et al; ISBN: 0824787722; http://www.amazon.com/exec/obidos/ASIN/0824787722/icongroupinterna
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Heart Failure: Cardiac Function and Dysfunction CD-ROM by Eugene Braunwald, Wilson S. Colucci; ISBN: 1573400599; http://www.amazon.com/exec/obidos/ASIN/1573400599/icongroupinterna
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Heart Failure: Diagnosis and Management by Andrew L. Clark (Editor), John J. V. McMurray (Editor) (2001); ISBN: 1853177172; http://www.amazon.com/exec/obidos/ASIN/1853177172/icongroupinterna
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Heart Failure: Diary of a Third Year Medical Student by Michael Greger; ISBN: 0967828805; http://www.amazon.com/exec/obidos/ASIN/0967828805/icongroupinterna
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Heart Failure: Frontiers in Cardiology by Akira Kitabatake (Editor), et al (2000); ISBN: 4431702393; http://www.amazon.com/exec/obidos/ASIN/4431702393/icongroupinterna
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Heart Failure: Management Issues in Primary Care by Paul H. Tanser (Editor); ISBN: 1895995078; http://www.amazon.com/exec/obidos/ASIN/1895995078/icongroupinterna
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Heart Failure: Pathophysiology, Molelcular Biology and Clinical Management by Arnold M. Katz; ISBN: 0781715490; http://www.amazon.com/exec/obidos/ASIN/0781715490/icongroupinterna
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Heart Failure: Providing Optimal Care by Mariell Jessup (Editor), Kathleen M. McCauley (Editor) (2003); ISBN: 1405103752; http://www.amazon.com/exec/obidos/ASIN/1405103752/icongroupinterna
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Heart Failure: Scientific Principles and Clinical Practice by Philip A. Poole-Wilson (Editor), et al; ISBN: 0443075018; http://www.amazon.com/exec/obidos/ASIN/0443075018/icongroupinterna
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Heart Failure: The Promise and Practice of Dopaminergic Agonists (American Journal of Noninvasive Cardiology, Vol. 5, Supplement 1, 1991) by S. Dalla Volta, et al (1991); ISBN: 3805553846; http://www.amazon.com/exec/obidos/ASIN/3805553846/icongroupinterna
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Heath over Heart Failure by Michael E. McIvor (2002); ISBN: 1928888046; http://www.amazon.com/exec/obidos/ASIN/1928888046/icongroupinterna
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Improving Outcomes in Chronic Heart Failure: A Practical Guide to Specialist Nurse Intervention by Simon Stewart, Lynda Blue (2001); ISBN: 0727916025; http://www.amazon.com/exec/obidos/ASIN/0727916025/icongroupinterna
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Improving Outcomes in Heart Failure: An Interdisciplinary Approach by Debra K. Moser (Editor), Barbara Riegel (Editor); ISBN: 0834216442; http://www.amazon.com/exec/obidos/ASIN/0834216442/icongroupinterna
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Initiating Therapy in Heart Failure: a Handbook for General Practice by Andrew Coats (1998); ISBN: 1873839448; http://www.amazon.com/exec/obidos/ASIN/1873839448/icongroupinterna
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Left Ventricular Diastolic Dysfunction and Heart Failure by William H., M.D. Gaasch, Martin M., M.D. Lewinter; ISBN: 0812115090; http://www.amazon.com/exec/obidos/ASIN/0812115090/icongroupinterna
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Living with Heart Failure: A Guide for Patients by Martin R. Cowie (2003); ISBN: 1904218229; http://www.amazon.com/exec/obidos/ASIN/1904218229/icongroupinterna
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Management of Heart Failure by Jay Cohn, Spencer Kubo (1991); ISBN: 0929240170; http://www.amazon.com/exec/obidos/ASIN/0929240170/icongroupinterna
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Management of Heart Failure by Nanette K. Wenger (Editor), Desmond G. Julian (Editor) (1986); ISBN: 0407022694; http://www.amazon.com/exec/obidos/ASIN/0407022694/icongroupinterna
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Management of Heart Failure; ISBN: 1901865843; http://www.amazon.com/exec/obidos/ASIN/1901865843/icongroupinterna
244 Heart Failure
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Managing Heart Failure in Primary Care by Henry Dargie (Editor), et al; ISBN: 0865429669; http://www.amazon.com/exec/obidos/ASIN/0865429669/icongroupinterna
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Managing Heart Failure in Primary Care: A Practical Guide by Martin R. Cowie, Mike Kirby (2003); ISBN: 1904218202; http://www.amazon.com/exec/obidos/ASIN/1904218202/icongroupinterna
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Mechanisms of Heart Failure (Developments in Cardiovascular Medicine, 167) by Pawan K. Singal, et al (1996); ISBN: 0792334906; http://www.amazon.com/exec/obidos/ASIN/0792334906/icongroupinterna
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Modern Management of Congestive Heart Failure by John Hamer; ISBN: 0853241643; http://www.amazon.com/exec/obidos/ASIN/0853241643/icongroupinterna
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Molecular Approaches to Heart Failure Therapy by G. Hasenfub (Editor), et al; ISBN: 3798512361; http://www.amazon.com/exec/obidos/ASIN/3798512361/icongroupinterna
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Natriuretic Peptides and Congestive Heart Failure (Medical Intelligence Unit) by ChiMing Wei (1999); ISBN: 0412114011; http://www.amazon.com/exec/obidos/ASIN/0412114011/icongroupinterna
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Optimising Heart Failure Management by Brigitte Stanek (Editor); ISBN: 0864710909; http://www.amazon.com/exec/obidos/ASIN/0864710909/icongroupinterna
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Pathophysiology of Heart Failure (Developments in Cardiovascular Medicine, 168) by Naranjan S. Dhalla (Editor), et al (1996); ISBN: 0792335716; http://www.amazon.com/exec/obidos/ASIN/0792335716/icongroupinterna
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Practical Approaches to the Treatment of Heart Failure by Roger M. Mills (Editor), James B. Young (Editor); ISBN: 0683181041; http://www.amazon.com/exec/obidos/ASIN/0683181041/icongroupinterna
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Recent Changes in the Treatment of Congestive Heart Failure: Satellite Symposium at the Joint Xiith World Congress of Cardiology & Xvith of the European Society of Cardiology, Berlin, September 1994 (Cardiology) by Peter A. Van Zwieten (Editor) (1997); ISBN: 3805565208; http://www.amazon.com/exec/obidos/ASIN/3805565208/icongroupinterna
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SHAPIRO CA HEART FAILURE PB (FOR MERCK); ISBN: 0723417164; http://www.amazon.com/exec/obidos/ASIN/0723417164/icongroupinterna
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Sudden Cardiac Death and Congestive Heart Failure: Diagnosis and Treatment by Symposium on New Drugs and Devices, et al; ISBN: 0898385806; http://www.amazon.com/exec/obidos/ASIN/0898385806/icongroupinterna
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Surgical Management of Congestive Heart Failure by James C. Fang (Editor), Gregory S. Couper (Editor) (2004); ISBN: 1588290344; http://www.amazon.com/exec/obidos/ASIN/1588290344/icongroupinterna
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Surgical Options for the Treatment of Heart Failure (DEVELOPMENTS IN CARDIOVASCULAR MEDICINE Volume 225) by Roy G. Masters (Editor); ISBN: 079236130X; http://www.amazon.com/exec/obidos/ASIN/079236130X/icongroupinterna
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Surgical Remodeling in Heart Failure: Alternative to Transplantation by W. Brett (Editor), et al (2000); ISBN: 379851223X; http://www.amazon.com/exec/obidos/ASIN/379851223X/icongroupinterna
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Tailoring Heart Failure Therapy by Ronnie Willenheimer, et al (2002); ISBN: 184184148X; http://www.amazon.com/exec/obidos/ASIN/184184148X/icongroupinterna
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The 2002 Official Patient's Sourcebook on Heart Failure by Icon Health Publications, et al (2002); ISBN: 0597831475; http://www.amazon.com/exec/obidos/ASIN/0597831475/icongroupinterna
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The Concept of Heart Failure from Avicenna to Albertini: From Avicenna to Albertini by Saul Jarcho (1980); ISBN: 0674156358; http://www.amazon.com/exec/obidos/ASIN/0674156358/icongroupinterna
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The No-Salt, Lowest-Sodium Cookbook : Hundreds of Favorite Recipes Created to Combat Congestive Heart Failure and Dangerous Hypertension by Donald A. Gazzaniga (Author), Michael B. Fowler (Introduction) (2001); ISBN: 0312252528; http://www.amazon.com/exec/obidos/ASIN/0312252528/icongroupinterna
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The Puzzle of Heart Failure: Putting the Pieces Together by Susan D. Allen, Colleen A. Holloran (1991); ISBN: 0916999092; http://www.amazon.com/exec/obidos/ASIN/0916999092/icongroupinterna
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Ultrafiltration in Congestive Heart Failure (Cardiology) by Rajnish Mehrotra (Editor), et al (2002); ISBN: 3805573804; http://www.amazon.com/exec/obidos/ASIN/3805573804/icongroupinterna
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Use and Approval of Antihypertensive Agents and Surrogate Endpoints for the Approval of Drugs Affecting Antiarrhythmic Heart Failure and Hypolipidemi: Proceedings of the Tenth Annual Symposium on New Drugs & Devices, October 31November 1, 1989 by Pa.)/ Morganroth, Joel Symposium on New Drugs and Devices 1989 Philadelphia (Editor), Joel Morganroth (1990); ISBN: 0792307569; http://www.amazon.com/exec/obidos/ASIN/0792307569/icongroupinterna
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Vasodilators in Chronic Heart Failure by H. Just (Editor) (1983); ISBN: 0387116168; http://www.amazon.com/exec/obidos/ASIN/0387116168/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “heart failure” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:8 •
8
Advances and controversies in cardiology: including the use of vasodilators in heart failure Author: Donoso, Ephraim.; Year: 1966; New York: Thieme-Stratton, 1981; ISBN: 0865770247
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
246 Heart Failure
http://www.amazon.com/exec/obidos/ASIN/0865770247/icongroupinterna •
Basic pathophysiological mechanisms of congestive heart failure: a programmed unit Author: Tripp, Alice.; Year: 1964; New York: McGraw-Hill, c1979; ISBN: 0070652236 http://www.amazon.com/exec/obidos/ASIN/0070652236/icongroupinterna
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Chemistry of heart failure, by William C. Holland and Richard L. Klein. Author: Holland, William C.,; Year: 1968; Springfield, Ill., Thomas [c1960]
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Congestive heart failure Author: Pinneo, Rose.; Year: 1968; New York: AppletonCentury-Crofts, 1978
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Congestive heart failure: mechanisms, evaluation and treatment Author: Mason, Dean T.; Year: 1968; New York: Dun-Donnelley, c1976; ISBN: 0914316052 http://www.amazon.com/exec/obidos/ASIN/0914316052/icongroupinterna
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Congestive heart failure [by] Ralph M. Myerson [and] Bernard H. Pastor. Author: Myerson, Ralph M.,; Year: 1964; St. Louis, Mosby, 1967
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Congestive heart failure Editor: Albert N. Brest. Author: Brest, Albert N.,; Year: 1965; [New York] Medcom Press [c1975]
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Congestive heart failure, edited by Charles K. Friedberg; assistant editor: Ephraim Donoso. With 29 contributors. Author: Friedberg, Charles K. (Charles Kaye),; Year: 1964; New York, Grune; Stratton, 1970; ISBN: 0808906704 http://www.amazon.com/exec/obidos/ASIN/0808906704/icongroupinterna
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Congestive heart failure. Author: Benack, Raymond Thomas,; Year: 2003; Springfield, Ill., Thomas [c1966]
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Congestive heart failure. [Editorial board: George W. Thorn, et al. Author: Thorn, George W. (George Widmer),; Year: 1964; San Juan, P. R., Searle; Co., 1972]
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Congestive heart failure; etiology, prevention, management. Author: United States. Public Health Service. Division of Chronic Diseases.; Year: 1965; Washington,
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Experimental cardiac hypertrophy and heart failure Author: Jacob, Ruthard.; Year: 1967; Darmstadt: Steinkopff, 1980; ISBN: 3798505772
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Heart failure Author: Fishman, Alfred P.; Year: 1967; Washington: Hemisphere Pub. Corp.; New York: McGraw-Hill, c1978; ISBN: 0070211183 http://www.amazon.com/exec/obidos/ASIN/0070211183/icongroupinterna
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Phentolamine in heart failure and other cardiac disorders: proceedings of an international workshop, London, November 1975 Author: Taylor, S. H. (Stanley Howard); Year: 1968; Bern: Huber, c1976; ISBN: 3456803796 http://www.amazon.com/exec/obidos/ASIN/3456803796/icongroupinterna
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Prevention of congestive heart failure recurrences [by] Saleem A. Farag and Harold N. Mozar. Author: Farag, Saleem A.; Year: 1964; [Berkeley] State of California, Dept. of Public Health, Bureau of Chronic Diseases, 1967
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Starling's law of the heart; its significance in chronic congestive heart failure. Author: Loe, Ping-kian.; Year: 2002; Djakarta, Keng Po, 1961
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Studies in acute heart failure Author: Bradley, Ronald D.; Year: 1968; London: Arnold, 1977; ISBN: 0713142952 http://www.amazon.com/exec/obidos/ASIN/0713142952/icongroupinterna
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Symposium on congestive heart failure. Author: Blumgart, Herrman Ludwig,; Year: 1965; New York, American
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The management of congestive heart failure Author: Gazes, Peter C.,; Year: 1966; Chicago: Year Book Medical Publishers, 1980
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The myocardium in hyperfunction, hypertrophy and heart failure. Prepared under the editorial supervision of Peter E. Pool. Author: Meerson, F. Z. (Feliks Zalmanovich); Year: 1962; New York, American
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Treatment of heart failure. Guest editor: Carleton B. Chapman. Treatment of intestinal malabsorption. Guest editor: H. Marvin Pollard. Author: Chapman, Carleton B. (Carleton Burke),; Year: 1962; [New York] Harper; Row [c1965]
Chapters on Heart Failure In order to find chapters that specifically relate to heart failure, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and heart failure 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 “heart failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on heart failure: •
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.
•
Congestive Heart Failure Source: in Mandal, A.K. and Nahman, N.S., Jr., eds. Kidney Disease in Primary Care. Baltimore, MD: Williams and Wilkins. 1998. p. 158-168.
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Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. E-mail:
[email protected]. PRICE: $39.95. ISBN: 0683300571. Summary: This chapter on congestive heart failure (CHF) is from a textbook that provides primary care physicians with practical approaches to common clinical problems of kidney diseases. The authors first provide background information on the pathophysiology of CHF, defining CHF as a clinical syndrome signaling the inability of the heart to maintain sufficient output to satisfy the metabolic requirements of the body. The authors then discuss diagnostic considerations; signs and symptoms, including functional classification, testing, and differential diagnosis; and treatment issues, including general principles, acute cardiogenic pulmonary edema, patients with mild symptoms, hypertensive crisis, medical therapy for left ventricular systolic and diastolic dysfunctions, associated conditions, and asymptomatic individuals with CHF. The chapter concludes with a discussion of prevention strategies, the indications for referring a patient to a specialist, and the answers to a list of questions commonly asked by patients diagnosed with CHF. The authors note that CHF is commonly seen in patients with renal disease. The precise determination of the presence and extent of underlying cardiac disease requires a careful history, physical examination, electrocardiographic and radiographic interpretation, and appropriate use of further imaging studies. With appropriate education, judicious use of medications, and longitudinal followup, the patient will not only live longer but also enjoy a better quality of life. 1 figure. 4 tables. 15 references.
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CHAPTER 8. MULTIMEDIA ON HEART FAILURE Overview In this chapter, we show you how to keep current on multimedia sources of information on heart failure. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on heart failure is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “heart failure” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, 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 “Videorecording (videotape, videocassette, etc.).” Type “heart failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on heart failure: •
Aging Brain Source: Sacramento, CA: Department of Aging. 1987. (videocassette, 6 handouts and 6 page training manual.). Contact: California Department of Aging, Training and Education Section. 1600 K Street, Sacramento, CA 95814. (916) 322-3110. PRICE: $10.00. Summary: This tape contains seven training segments designed for administrators and staff working in residential facilities for the aged. It reviews commonly held beliefs about aging that may negatively influence the care given to aging residents and how these myths developed. According to the tape, many believe that aged people are naturally "senile". Aged people can either accept this belief and act accordingly, creating a self-fulfilling prophecy in which they relinquish their independence to those caring for them, or they can rebel against their caregivers. Several studies related to aging are reviewed that suggest that there are only minor differences between the mental capacities of the young and aged. Treatable diseases that can affect the aged person's
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mental abilities are described including drug overdoses, malnutrition, dehydration, blood clots, brain tumors, depression, alcoholism, liver failure, kidney failure, drastic environmental changes, thyroid problems, heart failure, infections, diabetes, constipation, and emphysema. Organic brain syndromes, incurable diseases that affect mental capability, also are reviewed, including multi-infarct dementia, Pick's disease, Creutzfeldt-Jakob disease, Korsakoff's syndrome, Parkinson's disease, and Alzheimer's disease. Specific attention is given to changes in the brain that occur as the disease progresses, the symptoms, and possible risk factors and causes of the disease. Contact points for the Alzheimer's Association are provided for further information. •
Pediatric Hypertension Source: New Hyde Park, NY: Schneider Children's Hospital. 2000. (Videorecording). Contact: Available from Schneider Children's Hospital. 269-01 76th Avenue, Room 365, New Hyde Park, New York 11040-1432. (718) 470-3491. Fax: (718) 470-0887. Website: www.schneiderchildrenshospital.org. Summary: This videotape program educates parents and families of children who are diagnosed with hypertension (high blood pressure). The program is narrated by three health care providers: Dr. Julie Ingelfinger, Dr. Howard Trachtman, and Rachel Frank, a nephrology nurse. The program explains why it is vital to diagnose and manage pediatric hypertension, noting the role of long term hypertension in adult problems of heart attack, stroke, and congestive heart failure. The program reviews hypertension and its causes, treatment options, how to understand blood pressure readings (systolic and diastolic), classification of the different levels of hypertension, risk factors, diagnostic considerations and tests, and management options, including nutrition, drug therapy, weight control, exercise, relaxation methods, and refraining from smoking. The program features many interviews with children and parents and their health care providers.
Bibliography: Multimedia on Heart Failure The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in heart failure (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on heart failure: •
[Nutritional components in the care of the patient with congestive heart failure] [slide] Source: [sponsored by the Western New York Dietetic Association]; Year: 1971; Format: Nutritional components in the care of the patient with congestive heart failure; Buffalo, NY: Communications in Learning, [1971]
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Captopril and other agents used in the treatment of congestive heart failure [videorecording] Source: [presented by] Marshfield Clinic and St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983
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Chronic heart failure and vasodilator therapy [videorecording] Source: presented by the American College of Cardiology, ACCEL Program; written and produced by
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Sutherland Learning Associates, Inc; Year: 1980; Format: Videorecording; [Bethesda, Md.]: The College, c1980 •
Complications, heart failure [filmstrip] Source: Trainex; Year: 1983; Format: Filmstrip; Garden Grove, CA: Trainex, c1983
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Congestive heart failure [slide] Source: Committee on Medical Education of the American Heart Association; Year: 1974; Format: Slide; [New York: The Assn., 1974]
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Congestive heart failure [slide] Source: Miles Pharmaceuticals; [developed and produced by Gardiner-Caldwell SynerMed]; Year: 1985; Format: Slide; [S.l.]: GardinerCaldwell SynerMed, c1985
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Congestive heart failure [sound recording]: profile and management Source: American Society of Consultant Pharmacists; produced by Teach'em, inc; Year: 1978; Format: Sound recording; Chicago: Teach'em, [1978]
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Congestive heart failure [videorecording] Source: developed by Michael S. Shaw, Gerald Fletcher; [produced by] National Medical Audiovisual Center; Year: 1979; Format: Videorecording; [Bethesda, Md.]: Dept. of Health, Education, and Welfare, Public Health Service, National Institutes of Health, National Library of Medicine; [Washington: for sale by National Audiovisual Center], 1979
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Congestive heart failure [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983
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Congestive heart failure [videorecording] Source: produced by CED, Center for Educational Development, University of Illinois at Chicago, Health Sciences Center; Year: 1986; Format: Videorecording; Chicago, Ill.: Board of Trustees, the University of Illinois, c1986
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Congestive heart failure [videorecording]: update on diagnosis and treatment Source: author, Barry J. Crevey; participating cardiologist, Richard D. Judge; medical consultant, John R. Flynn; Year: 1984; Format: Videorecording; Chicago, Ill.: American Medical Association, c1984
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Congestive heart failure [videorecording]; cardiac tamponade in children Source: Dept. of Pediatrics, Emory University, School of Medicine; Year: 1978; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library], 1978
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Congestive heart failure and cardiac impedance [slide] Source: Michael Ritota; Year: 1979; Format: Slide; Newark, N. J.: M.E.D.S. Corp., c1979
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Congestive heart failure in children [videorecording] Source: presented by the Department of Pediatrics, Emory University, School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983
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Congestive heart failure, 1980 [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1980; Format: Videorecording; Atlanta: Emory Medical Television Network, 1980
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Controversies in heart failure [videorecording] Source: with Jay N. Cohn, Spencer H. Kubo, and Maria Teresa Olivari; Year: 1989; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1989
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Discharge planning of the patient with congestive heart failure [sound recording] Source: Niagara University, College of Nursing; Year: 1977; Format: Sound recording; Buffalo: Communications in Learning, 1977
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Heart failure [videorecording]: pressure overload Source: produced by the Medical Teaching Laboratories, Television Center, School of Medicine, University of North Carolina; Year: 1981; Format: Videorecording; Chapel Hill, NC: Health Sciences Consortium, 1981
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Heart failure in the elderly [sound recording] Source: Robert H. Sellers; [produced by] Communications in Learning; Year: 1975; Format: Sound recording; [Buffalo, N. Y.]: Communications in Learning, [1975]
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Management of congestive heart failure [videorecording] Source: [presented by] Audio-Video Digest Foundation, in collaboration with the University of California, San Franciso, School of Medicine; a Shotwell Image Group Production; Year: 1984; Format: Videorecording; Glendale, Calif.: The Foundation, c1984
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Management of congestive heart failure [videorecording] Source: produced by Virginia Hospital Television Network, Office of Continuing Education in Medicine and Allied Health Professions, Medical College of Virginia, Virginia Commonwealth University; Year: 1989; Format: Videorecording; [Richmond, Va.]: Medical College of Virginia, Virginia Commonwealth University, c1989
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Medical management of heart disease in children [videorecording]: heart failure and cardiac arrhythmias Source: Dorothy E. Brinsfield, William H. Plauth; [made by Georgia Regional Medical Television Network]; Year: 1972; Format: Videorecording; [Atlanta]: The Network: [for loan or sale by A. W. Calhoun Medical Library], c1972
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New approaches to the treatment of heart failure [videorecording] Source: presented by the Department of Medicine, Emory University, School of Medicine; Year: 1985; Format: Videorecording; Atlanta, Ga.: The University, 1985
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Role of vasodilators in congestive heart failure [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1983; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1983
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CHAPTER 9. PERIODICALS AND NEWS ON HEART FAILURE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover heart failure.
News Services and Press Releases One of the simplest ways of tracking press releases on heart failure 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 “heart failure” (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 heart failure. 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 “heart failure” (or synonyms). The following was recently listed in this archive for heart failure: •
Heart failure patients have better outcomes in private practice Source: Reuters Industry Breifing Date: November 28, 2003
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Heart failure patients do better outside hospitals Source: Reuters Health eLine Date: November 28, 2003
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Digoxin improves left atrial performance in heart failure patients Source: Reuters Industry Breifing Date: November 26, 2003
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Dendritic cells tied to autoimmune heart failure Source: Reuters Medical News Date: November 17, 2003
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Valsartan as effective as captopril in reducing mortality in heart failure Source: Reuters Medical News Date: November 10, 2003
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Novel drug may help fight severe heart failure Source: Reuters Industry Breifing Date: November 10, 2003
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Warm/cold therapy helpful in heart failure Source: Reuters Health eLine Date: November 07, 2003
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New diabetes drugs do raise heart failure risk Source: Reuters Health eLine Date: November 07, 2003
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Heart failure risk with thiazolidinediones quantified Source: Reuters Industry Breifing Date: November 07, 2003
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Cardiac proteins useful in gauging severity of heart failure Source: Reuters Medical News Date: November 07, 2003
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Saterinone improves hemodynamics in chronic heart failure Source: Reuters Industry Breifing Date: November 05, 2003
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BNP predicts mortality, urgency of transplantation in advanced heart failure Source: Reuters Medical News Date: October 28, 2003
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New arthritis drugs don't up heart failure risk Source: Reuters Health eLine Date: October 24, 2003
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Anti-TNF therapy does not increase heart failure risk in RA patients Source: Reuters Medical News Date: October 24, 2003
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Nutritional intake inadequate in heart failure patients Source: Reuters Medical News Date: October 21, 2003
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Heart failure patients need extra calories Source: Reuters Health eLine Date: October 21, 2003
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UK scientists to identify best stem cells for treating heart failure Source: Reuters Industry Breifing Date: October 16, 2003
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Pfizer's new heart failure drug wins FDA approval Source: Reuters Industry Breifing Date: October 08, 2003
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Pfizer wins FDA approval of Inspra for heart failure Source: Reuters Medical News Date: October 08, 2003
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Increased QRS duration predicts mortality in ICD recipients with heart failure Source: Reuters Medical News Date: October 08, 2003
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Autonomic nervous system affects response to exercise in chronic heart failure Source: Reuters Industry Breifing Date: October 07, 2003
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Guidant wins European OK for heart failure therapy Source: Reuters Industry Breifing Date: October 06, 2003
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Study suggests way to prevent heart failure Source: Reuters Health eLine Date: October 02, 2003
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Enzyme inhibition prevents heart failure in mice Source: Reuters Medical News Date: October 02, 2003
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Survival benefit linked to HRT in women with heart failure Source: Reuters Industry Breifing Date: September 30, 2003
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Pyridostigmine may be helpful in heart failure patients Source: Reuters Industry Breifing Date: September 30, 2003
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Insulin improves exercise performance in diabetics with heart failure Source: Reuters Medical News Date: September 29, 2003
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Arg389 variant predisposes to heart failure, ups response to beta-blockade Source: Reuters Medical News Date: September 18, 2003
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Metoprolol CR/XL benefits black patients with heart failure Source: Reuters Industry Breifing Date: September 15, 2003
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Beta-blocker may benefit blacks with heart failure Source: Reuters Health eLine Date: September 15, 2003
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Heart failure survival same for blacks or whites Source: Reuters Health eLine Date: September 10, 2003
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Heart failure survival rates similar in black and white patients Source: Reuters Medical News Date: September 10, 2003
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Thiazolidinediones linked to heart failure and pulmonary edema Source: Reuters Medical News Date: September 09, 2003
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Diabetes drugs may cause heart failure - report Source: Reuters Health eLine Date: September 09, 2003
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South Asians in UK at increased risk for heart failure, but less likely to die Source: Reuters Medical News Date: September 04, 2003
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Predictors of mortality not applicable in heart failure patients over age 75 Source: Reuters Medical News Date: September 01, 2003
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Oxygen uptake kinetics reflect prognosis in heart failure patients Source: Reuters Medical News Date: August 26, 2003
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Long-term exercise training has antiremodeling effect in heart failure patients Source: Reuters Medical News Date: August 07, 2003
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Urinary test could help gauge heart failure severity Source: Reuters Medical News Date: July 30, 2003
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Short-term statin therapy improves symptoms of nonischemic heart failure Source: Reuters Industry Breifing Date: July 28, 2003
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Novartis gets Swiss OK for Diovan in heart failure Source: Reuters Industry Breifing Date: July 24, 2003
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NICE says ACE inhibitors should be first line therapy for heart failure Source: Reuters Industry Breifing Date: July 22, 2003
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Aspirin may counteract ACE inhibitors in heart failure patients Source: Reuters Industry Breifing Date: July 16, 2003
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Heart failure due to LV systolic dysfunction common in paced patients Source: Reuters Industry Breifing Date: July 11, 2003
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Heart failure common in pacemaker patients Source: Reuters Health eLine Date: July 11, 2003
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Orion's heart failure drug to get German review Source: Reuters Industry Breifing Date: July 10, 2003
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Follow-up at nurse-led clinic can improve outcomes for heart failure patients Source: Reuters Medical News Date: July 10, 2003
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Vasogen begins enrollment for phase III chronic heart failure trial Source: Reuters Industry Breifing Date: July 09, 2003
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C-reactive protein level after acute MI predicts heart failure course Source: Reuters Medical News Date: July 04, 2003
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Diabetes drugs inappropriately prescribed for patients with concomitant heart failure Source: Reuters Industry Breifing Date: July 01, 2003 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 “heart failure” (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 “heart failure” (or synonyms). If you know the name of a company that is relevant to heart failure, 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/.
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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 “heart failure” (or synonyms).
Newsletters on Heart Failure Find newsletters on heart failure using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “heart failure.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “heart failure” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Kidney Disease Source: Sarcoidosis Networking. 8(3): 2. May-June 2000. Contact: Available from Sarcoid Network Association. Sarcoidosis Networking, 13925 80th Street East, Puyallup, WA 98372-3614. Email:
[email protected]. Summary: Sarcoidosis is a chronic, progressive systemic granulomatous (causing lesions) disease of unknown cause (etiology), involving almost any organ or tissue, including the skin, lungs, lymph nodes, liver, spleen, eyes, and small bones of the hands or feet. This brief article, from a newsletter for patients with sarcoidosis, reviews kidney disease, its types, diagnosis, and management. The article begins with a summary of the anatomy and function of the kidneys, which filter the blood (removing waste and excess body fluids), and maintain the balance of some essential nutrients helping to regulate blood pressure, red blood cells, and elements such as potassium and calcium. Without functioning kidneys, one cannot live without dialysis, the mechanical filtration of the blood. Kidneys fail for a variety of reasons, including trauma to the kidney, toxins, heart failure, obstruction (kidney stones), overuse of some medications, and diseases that invade the kidney, such as sarcoidosis. Diabetes and high blood pressure are the most common causes for loss of kidney function. Warning signs of kidney disease are high blood pressure (hypertension), blood or protein in the urine, creatinine level greater than 1.2 in women or 1.4 in men, more frequent urination (especially at night), difficult or painful urination, and puffy eyes or swelling of the hands or feet (especially in children). Loss of kidney function can produce symptoms including fatigue, weakness, nausea, vomiting, diarrhea or constipation, headaches, loss of appetite, increased edema (fluid retention), and fever or chills. Kidney failure is characterized as acute kidney failure, chronic kidney insufficiency, and chronic kidney failure. The need to put a person on dialysis depends upon the levels of creatinine and urea nitrogen in the blood and the evaluation of body parameters such as fluid status, and symptoms of toxicity. The author encourages readers to practice preventive measures which include drinking 8 to 10 glasses of water per day, preventing or treating diabetes and high blood pressure, avoiding tobacco, eating a well balanced diet, practicing good hygiene, treating wounds and infections, limiting exposure to heavy metals and toxic chemicals, and avoiding unnecessary over the counter drug use.
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “heart failure” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on heart failure: •
More Iron Overload Screening Recommended Source: Tufts University Health and Nutrition Letter. 18(11):7. January 2001. Contact: 10 High Street, Suite 706, Boston, MA 02110.
[email protected]. www.healthletter.tufts.edu. Summary: Iron overload, or hemochromatosis, is the most common genetic disorder in the United States, affecting about 5 people per 1,000. Hemochromatosis affects primarily Caucasians of northern European descent. Researchers at the University of Utah School of Medicine say that not enough men and women are screened for the disorder. Complications arise because the body absorbs too much iron from foods due to defective metabolism. The excess iron deposits itself in body tissues, causing everything from cirrhosis of the liver to arthritis to diabetes to congestive heart failure. Once the disorder is diagnosed, people have to go for bloodletting a few times a year in order to avoid the complications because much of the excess iron is stored in the red blood cells. The University of Utah research team believes that all Caucasians should undergo screening at least once in young adulthood. Screening involves a blood test that measures transferrin saturation, which is a marker for iron status.
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New Study Revisits Heart Valve Abnormalities Associated With Diet Drugs Source: WIN Notes. p. 3. Spring 2001. Contact: Weight-control Information Network. 1-877-WIN-4627. Summary: Julius Gardin, M.D., of the Division of Cardiology, the University of California, Irvine, examined the causal relationship between the appetite suppressants fenfluramine and dexfenfluramine and heart valve abnormalities. The study, originally published in the April 5, 2000, issue of the Journal of the American Medical Association (JAMA), found that these antiobesity agents are associated with an increase in the prevalence of some, but not all, valvular abnormalities. The study also explored whether these drugs are unrelated to serious cardiac events like heart attack, congestive heart failure, or ventricular arrhythmia. Participants were white obese females in their forties. Among patients who took the drugs for less than 3 months, no statistically significant difference in the prevalence of aortic regurgitation (AR) occurred between patients taking the appetite suppressants and those in the control group. With increasing exposure, prevalence rates increased. An accompanying JAMA editorial by Hershel Jick, M.D., of the Boston University School of Medicine, finds this duration effect as evidence of the causal relationship between the drugs and heart valve abnormalities. Jick agrees with Gardin and his colleagues that most drug-related cardiac abnormalities are minor and unlikely to advance to clinical disease.
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Nocturia: When Nature Calls at Night Source: Harvard Health Letter. 24(10): 6. August 1999. Contact: Available from Harvard Medical School Health Publications Group. Harvard Health Letter, P.O. Box 420300, Palm Coast, FL 32142-0300. (800) 829-9045. E-mail:
[email protected]. Summary: This health newsletter article describes nocturia, the condition of frequent urination at night. Nocturia is often more of a bother than a major burden, but readers are cautioned that it can be a sign of early kidney, bladder, or prostate disease. Nocturia can also be a byproduct of heart failure and other conditions that cause edema (retention of fluid). Physicians usually treat nocturia by addressing the conditions that cause it. More men in their 40s and 50s are bothered by nocturia than women the same age, but the numbers start to even out with age. For men, nocturia is often associated with prostate problems. In this situation, the bladder can't completely empty because benign prostatic hyperplasia (BPH), the noncancerous enlargement of the prostate gland, compresses the urethra and slows or impedes the flow of urine. For women, childbirth and lower estrogen levels cause the muscles of the pelvic floor to weaken. Weaker pelvic floor muscles can mean less control and more interruptions at night to urinate. The article concludes by encouraging readers to seek treatment for nocturia, particularly that which interferes with adequate sleep, as there are a variety of approaches to the problem. 1 figure.
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Hypertension Drugs: They Can Treat More Than High Blood Pressure Source: Mayo Clinic Health Letter. 17(11): 5. November 1999. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This health newsletter article reviews the drugs used to treat hypertension (high blood pressure). The author focuses on the additional benefits of these drugs. Not only do hypertension drugs help control elevated blood pressure, but some actually offer additional health benefits. These can include treating heart failure, diabetes, or symptoms resulting from an enlarged prostate. There are several types of hypertension drugs, and each type helps control elevated blood pressure in a different way. These include diuretics, beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, calcium channel blockers, alpha blockers, and central acting agents (central adrenergic inhibitors). In choosing drug therapy to treat a specific patient's hypertension, the physician will consider age, overall health, other medications already being taken, and cost considerations. One table outlines the possible additional health benefits these drugs have beyond treating elevated blood pressure. 1 table.
Academic Periodicals covering Heart Failure Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to heart failure. In addition to these sources, you can search for articles covering heart failure 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.”
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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 10. 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 heart failure. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with heart failure. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to heart failure: Amlodipine •
Systemic - U.S. Brands: Norvasc http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202670.html
Amlodipine and Benazepril •
Systemic - U.S. Brands: Lotrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203634.html
Angiotensin-Converting Enzyme (Ace) Inhibitors •
Systemic - U.S. Brands: Accupril; Aceon; Altace; Capoten; Lotensin; Mavik; Monopril; Prinivil; Univasc; Vasotec 4; Zestril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202044.html
Angiotensin-Converting Enzyme (Ace) Inhibitors and Hydrochlorothiazide •
Systemic - U.S. Brands: Accuretic; Capozide; Lotensin HCT; Prinzide; Uniretic; Vaseretic; Zestoretic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202045.html
Antidiabetic Agents, Sulfonylurea •
Systemic - U.S. Brands: Amaryl; DiaBeta; Diabinese; Dymelor; Glucotrol; Glucotrol XL; Glynase PresTab; Micronase; Orinase; Tolinase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202742.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
Beta-Adrenergic Blocking Agents and Thiazide Diuretics •
Systemic - U.S. Brands: Corzide 40/5; Corzide 80/5; Inderide; Inderide LA; Lopressor HCT; Tenoretic 100; Tenoretic 50; Timolide 10-25; Ziac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202088.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
Candesartan •
Systemic - U.S. Brands: Atacand http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203598.html
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Carvedilol •
Systemic - U.S. Brands: Coreg http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203636.html
Clonidine •
Systemic - U.S. Brands: Catapres; Catapres-TTS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202152.html
Clonidine and Chlorthalidone •
Systemic - U.S. Brands: Combipres http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202153.html
Diuretics, Loop •
Systemic - U.S. Brands: Bumex; Edecrin; Lasix; Myrosemide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202205.html
Diuretics, Potassium-Sparing •
Systemic - U.S. Brands: Aldactone; Dyrenium; Midamor http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202206.html
Diuretics, Potassium-Sparing, and Hydrochlorothiazide •
Systemic - U.S. Brands: Aldactazide; Dyazide; Maxzide; Moduretic; Spirozide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202207.html
Diuretics, Thiazide •
Systemic - U.S. Brands: Aquatensen; Diucardin; Diulo; Diuril; Enduron; Esidrix; Hydro-chlor; Hydro-D; HydroDIURIL; Hydromox; Hygroton; Metahydrin; Microzide; Mykrox; Naqua; Naturetin; Oretic; Renese; Saluron; Thalitone; Trichlorex 10; Zaroxolyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202208.html
Doxazosin •
Systemic - U.S. Brands: Cardura http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202629.html
Enalapril and Felodipine •
Systemic - U.S. Brands: Lexxel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203638.html
Eprosartan •
Systemic - U.S. Brands: Teveten http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500044.html
Guanabenz •
Systemic - U.S. Brands: Wytensin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202271.html
266 Heart Failure
Guanadrel •
Systemic - U.S. Brands: Hylorel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202272.html
Guanethidine •
Systemic - U.S. Brands: Ismelin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202273.html
Guanfacine •
Systemic - U.S. Brands: Tenex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202275.html
Hydralazine and Hydrochlorothiazide •
Systemic - U.S. Brands: Apresazide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202286.html
Indapamide •
Systemic - U.S. Brands: Lozol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202296.html
Irbesartan •
Systemic - U.S. Brands: Avapro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203379.html
Losartan •
Systemic - U.S. Brands: Cozaar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202767.html
Losartan and Hydrochlorothiazide •
Systemic - U.S. Brands: Hyzaar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203639.html
Mecamylamine •
Systemic - U.S. Brands: Inversine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202340.html
Metformin •
Systemic - U.S. Brands: Glucophage http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202756.html
Methyldopa •
Systemic - U.S. Brands: Aldomet http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202359.html
Methyldopa and Thiazide Diuretics •
Systemic - U.S. Brands: Aldoclor; Aldoril http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202360.html
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Minoxidil •
Systemic - U.S. Brands: Loniten http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202373.html
Nateglinide •
Systemic - U.S. Brands: Starlix http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500277.html
Nisoldipine •
Systemic - U.S. Brands: Sular http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203431.html
Nitrates Oral •
Systemic - U.S. Brands: Dilatrate-SR; IMDUR; ISDN; ISMO; Isordil Tembids; Isordil Titradose; Monoket; Nitrocot; Nitroglyn E-R; Nitrong; Nitro-par; Nitrotime; Sorbitrate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202411.html
Nitrates Sublingual, Chewable, or Buccal •
Systemic - U.S. Brands: Isordil; Nitrogard; Nitrostat; Sorbitrate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202412.html
Nitrates Topical •
Systemic - U.S. Brands: Deponit; Minitran; Nitro-Bid; Nitrodisc; Nitro-Dur; Nitrol; Transderm-Nitro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202413.html
Prazosin •
Systemic - U.S. Brands: Minipress http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202475.html
Prazosin and Polythiazide •
Systemic - U.S. Brands: Minizide http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202476.html
Rauwolfia Alkaloids •
Systemic - U.S. Brands: Harmonyl; Raudixin; Rauval; Rauverid; Serpalan; Wolfina http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202503.html
Rauwolfia Alkaloids and Thiazide Diuretics •
Systemic - U.S. Brands: Demi-Regroton; Diupres; Diurigen with Reserpine; Diutensen-R; Enduronyl; Enduronyl Forte; Oreticyl; Oreticyl Forte; Rauzide; Regroton http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202504.html
268 Heart Failure
Reserpine, Hydralazine, and Hydrochlorothiazide •
Systemic - U.S. Brands: Cam-Ap-Es; Cherapas; Ser-A-Gen; Seralazide; Ser-ApEs; Serpazide; Tri-Hydroserpine; Unipres http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202506.html
Telmisartan •
Systemic - U.S. Brands: Micardis http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203710.html
Terazosin •
Systemic - U.S. Brands: Hytrin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202546.html
Torsemide •
Systemic - U.S. Brands: Demadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202740.html
Trandolapril and Verapamil •
Systemic - U.S. Brands: Tarka http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203641.html
Valsartan •
Systemic - U.S. Brands: Diovan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203478.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.
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Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
9
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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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.10 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:11 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
10
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). 11 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “heart failure” (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 85060 880 1005 217 113 87275
HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “heart failure” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
12
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
13
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). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16
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 Biologists17 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.18 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.19 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/.
17 Adapted 18
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. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on heart failure 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 heart failure. 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 heart failure. 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 “heart failure”:
280 Heart Failure
•
Guides on heart failure Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html
•
Other guides Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.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
Within the health topic page dedicated to heart failure, the following was listed: •
General/Overviews Congestive Heart Failure http://www.nlm.nih.gov/medlineplus/tutorials/congestiveheartfailureloader.htm l JAMA Patient Page: Heart Failure Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZDTE35VWC &sub_cat=73 Learning about Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=337
•
Diagnosis/Symptoms Blood Tests: Seeking Clues about Your Hearts Health Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HB00016 BNP Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/bnp/test.html Chest X-Rays: Helping Detect Heart and Lung Conditions Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HB00019 Echocardiogram http://www.nlm.nih.gov/medlineplus/tutorials/echocardiogramloader.html Echocardiogram Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HB00012
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Echocardiogram Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/procdiag/echocardiogram.pdf Heart Failure: Tests Source: North American Society of Pacing and Electrophysiology http://www.naspe-patients.org/patients/heart_disorders/heart_failure/tests.html Signs and Symptoms of Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=339 •
Treatment Angiotensin Receptor Blockers http://circ.ahajournals.org/cgi/reprint/107/24/e215.pdf Cardiac Resynchronization Therapy: A Patient's Guide http://circ.ahajournals.org/cgi/reprint/108/9/e64.pdf Medications Commonly Used to Treat Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=118 Treatment Options for Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1598
•
Nutrition Cutting Down on Salt Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=336 Eating Out Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=317 Importance of Potassium Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=331 Limiting Fats and Cholesterol Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=323 Tips for Healthy Cooking Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=355 Tracking What You Drink Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=357 Understanding Diet Terms Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=340
282 Heart Failure
•
Coping Traveling with Oxygen: Planning Is Key Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01555
•
Specific Conditions/Aspects Cardiac Asthma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00121 Heart Failure: Risk Factors Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/heart_disorders/heart_failure/risk_factors.html Heart Failure: What to Ask Your Doctor Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/heart_disorders/heart_failure/what_to_ask_your_doctor.ht ml Heart Failure: When to See a Specialist Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/heart_disorders/heart_failure/when_to_see_a_specialist.htm l Sex and Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=359 Working with Your Doctor: Quick Tips Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1655
•
Latest News FDA Approves Inspra for Improving Survival of Congestive Heart Failure Patients After a Heart Attack Source: 10/08/2003, Food and Drug Administration http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01254.html Heart Failure Care Inconsistent Source: 11/09/2003, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3016913 Heart Failure Patients Do Better Outside Hospitals Source: 11/28/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14889 .html New Diabetes Drugs Do Raise Heart Failure Risk Source: 11/07/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14571 .html
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Warm/Cold Therapy Helpful in Heart Failure Source: 11/07/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14578 .html •
Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 Heart Failure Information and Education Source: Heart Failure Society of America http://www.abouthf.org/default.htm National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ North American Society of Pacing and Electrophysiology http://www.naspe.org/
•
Prevention/Screening Heart Failure: Prevention Source: North American Society of Pacing and Electrophysiology http://www.naspepatients.org/patients/heart_disorders/heart_failure/prevention.html MEDLINEplus: Heart Diseases--Prevention Source: National Library of Medicine http://www.nlm.nih.gov/medlineplus/heartdiseasesprevention.html
•
Research Evaluation of Risk Factors for Congestive Heart Failure Source: American College of Physicians http://www.annals.org/cgi/content/full/138/1/I-22 Exercise, the Right Prescription for Patients with Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3009555 Heart Failure Care Inconsistent Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3016913 Heart Failure Patients Have Lower Death Rates Under Cardiologists' Care Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3013009 Insulin-like Growth Factor I Levels and Heart Failure Risk in Older People Source: American College of Physicians http://www.annals.org/cgi/content/full/139/8/I-22 NHLBI Study Finds Improved Heart Failure Survival Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/oct2002/nhlbi-30.htm
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NHLBI's Framingham Heart Study Finds Overweight/Obesity and Risk for Heart Failure Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/jul2002/nhlbi-31.htm
Strong
Link
between
Screening for Asymptomatic Heart Failure Source: American College of Physicians http://www.annals.org/cgi/content/full/138/11/I-51 Tumor Necrosis Factor Antagonists and Heart Failure Source: American College of Physicians http://www.annals.org/cgi/content/full/138/10/I-48 You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on heart failure. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Guide to Diagnosis: Hemochromatosis Iron Overload Source: Greenville, SC: Iron Disorders Institute. 1999. [2 p.]. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (888) 565-IRON. Website: www.irondisorders.org. PRICE: Single copy free. Summary: Hemochromatosis (HHC) is a genetic metabolic disorder in which an individual absorbs and retains too much iron. Increased iron absorption in the gastrointestinal tract may cause lifelong excessive iron absorption and accumulation, and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death can result. This brochure offers readers a guide to the diagnosis of HHC. Topics include symptoms, risk factors, candidacy for liver biopsy, tests for body iron status overload, DNA tests, indications for genetic testing, and the importance of working closely with one's physician. Chronic fatigue is generally the first and most common symptom associated with iron overload. Liver biopsy may be recommended if the patient's liver enzymes are elevated and ferritin is about 1,000 ng per milliliter. Liver biopsy is the only way to determine the extent of cirrhosis or fibrosis and formerly was the standard for diagnosing hemochromatosis. Trial phlebotomy (blood removal) is also a way to diagnose HHC. A patient who can tolerate several phlebotomies without developing anemia can be diagnosed with HHC. Genetic typing tests for HHC are available as well. Children do not need to be genetically tested. Once it is determined
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that parents are carriers or homozygous, offspring should be screened routinely using transferrin saturation percentage and ferritin test levels. The brochure notes that most patients with HHC can be diagnosed and treated by a family practice physician; however, specialists may also be necessary to treat chronic disease that may have developed as a result of iron overload. The brochure concludes with a brief description of the Iron Disorders Institute (IDI), founded to limit pain, suffering, and unnecessary death from common and often misdiagnosed disorders of iron, such as anemia of chronic disease, porphyria cutanea tarda, iron loading anemia, iron deficiency anemia, African siderosis, and HHC. •
Guide to Treatment: Hemochromatosis Iron Overload Source: Greenville, SC: Iron Disorders Institute. 1999. 17 p. Contact: Available from Iron Disorders Institute. P.O. Box 2031, Greenville, SC 29602. (888) 565-IRON. Website: www.irondisorders.org. PRICE: Single copy free. Summary: Hemochromatosis is a genetic metabolic disorder in which an individual absorbs and retains too much iron. Increased iron absorption in the gastrointestinal tract may cause lifelong excessive iron absorption and accumulation, and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death can result. This brochure offers readers a guide to the treatment for hemochromatosis. Topics include diagnostic tests, the technique of phlebotomy (removing blood), estimating the number of treatments, dietary considerations, foods high in iron, the patient care team, and treatment journals. For patients with serious iron overload, phlebotomy is necessary because it removes about 250 milligrams of iron with each treatment. The brochure describes each step of the phlebotomy treatment, from undergoing pretreatment blood tests, to preparing the arm for blood extraction, measuring the amount of blood removed, providing postprocedure care, and handling the removed blood (which is under the same guidelines as contaminated blood). The brochure outlines four phases of therapy (including maintenance) and what the patient can expect during each phase; the issue of vitamin supplementation is also addressed. Supplements may include vitamin E, B complex (without C) plus extra B6, folic acid, and B12. Dietary changes include educating oneself about the amounts of iron in foods and adjusting intake appropriately. Meat contains the most easily absorbable form of iron; vegetables and grains have a type of iron that is not easily absorbed. The brochure includes a list of common foods with their iron content (the amount in a standard serving). The brochure also includes a blank treatment journal for recording one's phlebotomy procedures and a blank lined page for recording important phone numbers. The brochure concludes with a brief description of the Iron Disorders Institute (IDI), founded to limit pain, suffering, and unnecessary death from common and often misdiagnosed disorders of iron, such as anemia of chronic disease, porphyria cutanea tarda, iron loading anemia, iron deficiency anemia, African siderosis, and hereditary hemochromatosis. 7 figures. 2 tables.
•
About High Blood Pressure: Control, Risk, Lifestyle, Weight Source: Dallas, TX: American Heart Association. 1995. 17 p. Contact: Available from Channing L. Bete Company/American Heart Association Fulfillment Center. 200 State Road, South Deerfield, MA 01373-0200. (800) 611-6083. Fax (800) 499-6464. E-mail:
[email protected]. PRICE: $7.50 for 50 copies. Summary: This booklet provides basic information about hypertension (high blood pressure). The booklet notes that adults have hypertension if their blood pressure
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remains above the threshold of 140 over 90. Approximately 90 percent of the cases of high blood pressure have no known causes. However, researchers have determined that some controllable risk factors for high blood pressure include obesity, excessive salt intake, excessive alcohol consumption, lack of exercise, and stress. Uncontrollable risk factors include race, heredity, and age. The booklet points out that an inactive lifestyle makes it easier for people to become overweight and therefore increases the chance of high blood pressure. High blood pressure has no symptoms, so adults should have a health care professional check their blood pressure at least once a year. Although high blood pressure cannot be cured, it can usually be controlled. When compared with people who have controlled high blood pressure, people with uncontrolled high blood pressure are on average three times more likely to develop coronary heart disease, six times more likely to develop congestive heart failure, and seven times more likely to have a stroke. Most treatments for high blood pressure involve a combination of diet, exercise, and medication. The booklet concludes with a list of related brochures available from the American Heart Association. •
What's It Going to Cost You? Syphilis Contact: Spence Research, Incorporated, Health Educo, 5045 Franklin Ave, Waco, TX, 76702, (817) 776-6461. Summary: This brochure for the general public discusses the sexually transmitted disease (STD), syphilis. Individuals who have any symptoms of syphilis should be tested by a healthcare provider immediately. The brochure identifies the symptoms of primary, secondary, and tertiary syphilis. Syphilis can be spread through oral, anal, or vaginal contact or through contact with an open lesion. Practicing sexual abstinence, monogamy, or safer sex with condoms can prevent syphilis. Individuals can further reduce their risk for contracting syphilis by avoiding substance abuse, which affects decision-making abilities. Syphilis is often treated by the drug benzathine penicillin. However, it is not always effective in persons with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). If syphilis is left untreated, it can cause meningitis, heart failure, brain and spinal cord damage, psychosis, dementia, and/or death. The brochure outlines the average costs for the treatment of syphilis. Contact information is provided for the Centers for Disease Control and Prevention's (CDC) National STD Hotline and for the American Social Health Association (ASHA).
•
Thinking About Lowering Your Blood Pressure Source: Midland, MI: Health Enhancement Systems. 1999. 2 p. Contact: Available from Health Enhancement Systems. P.O. Box 1035, Midland, MI 48641-1035. (800) 326-2317. Fax (517) 839-0025. PRICE: $0.68 each for a pack of 10 to 50 brochures; bulk quantities available; plus shipping and handling. Item number HESBP1. Summary: This brochure introduces the concept of blood pressure and the reasons why it is important to monitor and treat high blood pressure (hypertension). Blood pressure is a measurement of the force of blood pushing against the artery walls. The top number, systolic pressure, is the force when the heart beats and sends blood into the arteries. The bottom number, diastolic pressure, is the force when the heart is resting between beats. Each heart beat produces a slightly different pressure, but both numbers tend to go up and down together. High blood pressure refers to increased tension or pressure in the arteries. Hypertension increases the risk of serious medical conditions such as heart attack, stroke, kidney failure, and congestive heart failure. The brochure
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notes that many people do not feel the urgency to treat hypertension because it does not create symptoms as some other health concerns do. The brochure encourages readers to think about hypertension and the importance of addressing this potentially deadly medical condition. The brochure asks readers to consider four questions that ask how the reader would respond if a close friend or family member had hypertension that needed treatment. The brochure provides blank space for readers to answer the questions, then lists resources through which readers can obtain more information. •
Benefits of Lowering Your Blood Pressure Source: Midland, MI: Health Enhancement Systems. 1999. 6 p. Contact: Available from Health Enhancement Systems. P.O. Box 1035, Midland, MI 48641-1035. (800) 326-2317. Fax (517) 839-0025. PRICE: $0.98 each for a pack of 10 to 50 brochures; bulk quantities available; plus shipping and handling. Item number HESBP2. Summary: This brochure is addressed to readers with high blood pressure (hypertension) who need encouragement to treat their condition. Hypertension increases the risk of serious medical conditions such as heart attack, stroke, kidney failure, and congestive heart failure. The brochure notes that many people do not feel the urgency to treat hypertension because it does not create symptoms as some other health concerns do. The brochure first outlines the risk factors that can be controlled, including weight, exercise, alcohol, salt intake, and smoking, then notes the additional risk factors including heredity, race, age, and gender. The brochure encourages readers to learn about the advantages of controlling high blood pressure and to think about the changes that may be required in order to control hypertension. Blank space is provided to answer directed questions about these changes. The brochure then offers a guided imagery exercise in which the reader pictures himself or herself undertaking and succeeding at the lifestyle changes that would be required. The brochure includes a section for readers to monitor and record their blood pressure readings at different times of day for a week; space is then provided to answer questions about the results of this blood pressure record. Two final sections offer strategies for learning more about hypertension and the things that a supportive friend or spouse can provide. The brochure serves as a type of self-contract for getting readers committed to their own health care plan. The brochure concludes with a list of three resource organizations that can provide additional information and assistance.
•
My Healthy Heart Source: Minneapolis, MN: International Diabetes Center. 1997. 4 p. Contact: Available from Park Nicollet Health Source. 3800 Park Nicollet Boulevard, Minneapolis, MN 55416. (800) 372-7776 or (612) 993-3534. Fax (612) 993-1840. PRICE: $1.25 each for 10-49 copies; $1.12 each for 50-99 copies; $1.03 each for 100-499 copies. ISBN: 188511544X. Summary: This brochure provides people who have diabetes with information about caring for their hearts. The brochure points out that heart disease is the direct cause of 55 percent of deaths among people with diabetes. Although chest pain (angina), heart attack, and congestive heart failure often seem to appear suddenly, they are almost always the result of years of slow damage to the blood vessels and heart. The brochure advises readers to review their blood glucose control and blood pressure at each visit with a health care professional. The brochure includes a description and a target value for each of the following necessary tests: HbA1c, total cholesterol, LDL cholesterol, HDL
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cholesterol, triglycerides, and blood pressure. The risk of heart disease can be reduced by controlling blood glucose, refraining from smoking, eating a diet low in saturated fat, getting regular exercise, and balancing stress. If lifestyle changes alone are insufficient, it may be necessary to take medications which help to lower cholesterol and blood pressure. Two sidebars provide space for recording test results and a list of medications and their functions. The brochure also includes a questionnaire designed to assess risk. (AA-M). •
Inside Look at Diabetes and Cardiovascular Disease Source: South Deerfield, MA: Channing L. Bete Co., Inc. 2000. 15 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $1.60 each; plus shipping and handling; quantity discounts available. Order number 75504. Summary: This illustrated booklet provides people who have diabetes with information on the relationship between diabetes and cardiovascular disease (CVD). Some types of CVD include coronary heart disease, stroke, and heart failure. Higher than normal levels of blood glucose may lead to unhealthy blood lipid levels. CVD risk factors that can be controlled include high cholesterol, smoking, high blood pressure, body weight, and lack of physical activity. The booklet provides guidelines for reducing CVD risk by lowering blood pressure, controlling blood sugar, improving cholesterol levels, losing weight, eating healthy food, exercising, quitting smoking, and taking appropriate medications. The booklet includes a list of organizations that can provide additional information about diabetes and cardiovascular disease.
•
Be Wise, Immunize!: Vaccinate on Time Source: Cleveland, OH: Learning Curve of Weingart Design. 199x. [2 p.]. Contact: Available from Learning Curve of Weingart Design. 4614 Prospect Avenue, Number 421, Cleveland, OH 44103-4314. (800) 795-9295. Fax (216) 881-7177. Website: www.learningcurve1.com. PRICE: $10.00 for a pack of 100; single copies are not available. Summary: This oversized bookmark lists the latest recommendations for pediatric immunizations from the Centers for Disease Control (CDC). The bookmark reminds parents that getting the shots (vaccinations) and getting all of them, is one of the most important things they can do for their babies. The front of the bookmark lists the age and recommended immunizations. The reverse side lists each of the immunizations and briefly notes what each one covers. Included are vaccines against hepatitis B, which causes liver damage; Hib (haemophilus influenzae b), which causes brain infection and brain damage; DTP or DTaP, which protects against diphtheria (serious breathing problems that can lead to paralysis and heart failure), pertussis (whooping cough), and tetanus (causes painful muscle spasms leading to lockjaw); polio (OPV), a disease that can paralyze arms and legs; MMR, measles, mumps, and rubella (rubella is German measles, a more serious form of measles that can lead to birth defects in babies); and varicella, or chicken pox. The schedule printed on the front of the bookmark is recommended by the American Academy of Pediatrics and the American Academy of Family Physicians.
•
Pulmonary Hypertension Source: Danvers, MA: Scleroderma Foundation. 1998. 6 p.
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Contact: Available from Scleroderma Foundation. 12 Kent Way, Suite 101, Byfield, MA 01922. (800) 722-4673 or (978) 463-5843. Fax (978) 463-5809. E-mail:
[email protected]. Website: www.scleroderma.org. PRICE: Single copy $1.00. Summary: This pamphlet for people with scleroderma uses a question and answer format to provide information about pulmonary artery hypertension. This type of high blood pressure involves the arteries that take blood from the right side of the heart to the lungs. The pamphlet describes the types of pulmonary artery hypertension that occur in scleroderma, including hypertension with or without scarring of the lung tissue. It also presents the symptoms of pulmonary artery hypertension, highlights the tests that might be conducted to diagnose pulmonary artery hypertension, explains the natural course of this condition in scleroderma, and discusses options for treating this type of hypertension. Pulmonary hypertension not related to scleroderma may be treated with oxygen therapy and anticoagulation therapy. Right-heart failure may be treated with various medications, including calcium channel blockers, diuretics, and an experimental drug known as prostacyclin. In addition, the pamphlet presents the mission of the Scleroderma Foundation.
The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “heart failure” (or synonyms). The following was recently posted: •
A guideline for the management of heart failure Source: National Heart Foundation of New Zealand - Disease Specific Society; 1996 (revised 2001 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3309&nbr=2535&a mp;string=heart+AND+failure
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ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evalua Source: American College of Cardiology Foundation - Medical Specialty Society; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3114&nbr=2340&a mp;string=heart+AND+failure
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Congestive heart failure in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jan); 71 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3165&nbr=2391&a mp;string=heart+AND+failure
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•
Diagnosis and treatment of heart failure due to left ventricular systolic dysfunction. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 February; 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2906&nbr=2132&a mp;string=heart+AND+failure
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Guidelines for the diagnosis and treatment of chronic heart failure Source: European Society of Cardiology - Medical Specialty Society; 2001 September; 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2976&nbr=2202&a mp;string=heart+AND+failure
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Heart failure Source: American Medical Directors Association - Professional Association; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3303&nbr=2529&a mp;string=heart+AND+failure
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Heart failure - systolic dysfunction Source: University of Michigan Health System - Academic Institution; 1999 August; 12 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2282&nbr=1508&a mp;string=heart+AND+failure
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Heart Failure Society of America guidelines for management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches Source: Heart Failure Society of America, Inc - Disease Specific Society; 1999 December; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2736&nbr=1962&a mp;string=heart+AND+failure Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:
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Facts About Heart Failure Summary: Heart failure is one of the most serious symptoms of heart disease. This fact sheet describes, the prevalence, causes, symptoms and treatment of this cardiovascular disorder. Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2010
•
Living With Heart Failure: Information and Support for Patients and Caregivers Summary: An educational and support tool for heart failure patients and their families. Source: American Heart Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5020 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 heart failure. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to heart failure. By consulting all of associations listed
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in this chapter, you will have nearly exhausted all sources for patient associations concerned with heart failure. 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 heart failure. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “heart failure” (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 “heart failure”. 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 “heart failure” (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 “heart failure” (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.20
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
20
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)21: •
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
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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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/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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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/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
21
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
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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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
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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
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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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/
Finding Medical Libraries
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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
•
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 heart failure: •
Basic Guidelines for Heart Failure Heart failure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000158.htm
•
Signs & Symptoms for Heart Failure Abnormal heart sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003266.htm Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm
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Decreased alertness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Decreased urine production Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Difficulty sleeping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Enlarged liver Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Excessive tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Faintness 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 Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Heart sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003266.htm Heartburn Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003114.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Hypotension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm
Online Glossaries 303
Indigestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003260.htm Irregular heartbeat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Light headedness 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 Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Need to urinate at night Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Nocturia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Obesity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003101.htm Oliguria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Palpitations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Peripheral edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm Rapid heartbeat 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 Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Swelling of feet Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm
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Swelling of the abdomen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003122.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Weight gain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003084.htm Weight gain (unintentional) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003084.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •
Diagnostics and Tests for Heart Failure ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Blood chemistry Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003468.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Chest CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003788.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 Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm Creatinine clearance Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003611.htm
Online Glossaries 305
CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Dialysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003421.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Heart catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003419.htm Heart catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003876.htm MUGA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003822.htm Nuclear heart scans Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003822.htm Paracentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003896.htm Pericardiocentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003872.htm Pleural fluid analysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003624.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm RNV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003822.htm Serum sodium Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003481.htm Swan-Ganz (right heart catheterization) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003870.htm Thoracentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003420.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm
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Urine specific gravity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003587.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •
Surgery and Procedures for Heart Failure Heart transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003003.htm
•
Background Topics for Heart Failure Alcohol consumption Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001944.htm Auscultation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002226.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Heart diseases Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000147.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Kidney disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000457.htm Physical activity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Precipitating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002275.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Systemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002294.htm
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Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
309
HEART FAILURE 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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [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] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]
Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] 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] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Actomyosin: A protein complex of actin and myosin occurring in muscle. It is the essential contractile substance of muscle. [NIH]
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Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] 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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [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 insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]
Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH]
Dictionary 311
Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [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] 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] Afterload: The tension produced by the heart muscle after contraction. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [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] Aged, 80 and Over: A person 80 years of age and older. [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] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine.
312 Heart Failure
Albuminuria may be a sign of kidney disease. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Aldosterone Antagonists: Compounds which inhibit or antagonize the biosynthesis or actions of aldosterone. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [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] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] 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] 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] 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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH]
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Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [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] 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] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] 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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] 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] Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] 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] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin converting enzyme 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.
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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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [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] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Anthranilic Acids: Benzoic acids which are substituted with an amino group in the C-2 position. [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] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage
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causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [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] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Coarctation: Narrowing of the lumen of the aorta, caused by deformity of the aortic media. [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] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to
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phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
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] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrial Flutter: Rapid, irregular atrial contractions due to an abnormality of atrial excitation. [NIH]
Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU]
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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] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [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] 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH]
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Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]
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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzamides: Benzoic acid amides. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [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] 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
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fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical Phenomena: Biochemical functions, activities, and processes at organic and molecular levels in humans, animals, microorganisms, and plants. [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 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] Biophysics: The science of physical phenomena and processes in living organisms. [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] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH] Bisoprolol: A cardioselective beta-1-adrenergic blocker. It is effective in the management of
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hypertension and angina pectoris. [NIH] 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] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] 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]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [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] Body Regions: Anatomical areas of the body. [NIH] Body Temperature Regulation: The processes of heating and cooling that an organism uses to control its temperature. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone 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] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the
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blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] 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] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] 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]
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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] 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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbenicillin: Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function. [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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH]
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Cardiac Glycosides: Substances obtained from species of Digitalis, Strophanthus, and other plants that contain specific steroid glycosides or their semisynthetic derivatives and used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the Na(+)-K(+)-exchanging ATPase and they are often used in cell biological studies for that purpose. [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] 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] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [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]
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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] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] 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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as
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metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Degranulation: The process of losing secretory granules (secretory vesicles). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [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 Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell 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] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoreceptors: Cells specialized to detect chemical substances and relay that information
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centrally in the nervous system. Chemoreceptors may monitor external stimuli, as in taste and olfaction, or internal stimuli, such as the concentrations of oxygen and carbon dioxide in the blood. [NIH] 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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholelithiasis: Presence or formation of gallstones. [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] 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 Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citric Acid Cycle: A series of reactions involving oxidation of a two-carbon acetyl unit to carbon dioxide and water with the production of high-energy phosphate bonds by means of tricarboxylic acid intermediate. [NIH]
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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] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] 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] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] 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] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [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] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [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,
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hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the 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] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH]
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Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] 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] 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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] 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
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aggregation phenomena. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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] 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] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH]
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Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Counterpulsation: A technique for assisting the circulation by decreasing the afterload of the left ventricle and augmenting the diastolic pressure. It may be achieved by intra-aortic balloon, or by implanting a special pumping device in the chest, or externally by applying a negative pressure to the lower extremities during cardiac systole. [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 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] Criterion: A standard by which something may be judged. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] 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] 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]
Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types,
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including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytopenia: A reduction in the number of blood cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] 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]
Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] 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] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by
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rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of 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] 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] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] 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] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexfenfluramine: The S-isomer of fenfluramine. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity. [NIH] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of
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vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetes, Gestational: Either symptomatic diabetes or impaired glucose tolerance induced by pregnancy but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (pregnancy in diabetics). [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 and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic heart failure: Inability of the heart to relax properly and fill with blood as a result of stiffening of the heart muscle. [NIH] Diastolic pressure: The lowest pressure to which blood pressure falls between contractions of the ventricles. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive 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
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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] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilate: Relax; expand. [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] 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] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disopyramide: Alpha-(2-(Bis(l-methylethyl)amino)ethyl)-alpha-phenyl-2-pyridine acetamide. A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] 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
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consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [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] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] 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] 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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance
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which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duke: A lamp which produces ultraviolet radiations for certain ophthalmologic therapy. [NIH]
Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]
Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [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] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] 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] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Elastin: The protein that gives flexibility to tissues. [NIH]
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Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] 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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] 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] 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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] 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 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] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH]
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Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] 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] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] 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] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [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]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH]
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Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
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
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distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]
Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture
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dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Membrane Oxygenation: Application of a life support system that circulates the blood through an oxygenating system, which may consist of a pump, a membrane oxygenator, and a heat exchanger. Examples of its use are to assist victims of smoke inhalation injury, respiratory failure, and cardiac failure. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] 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] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [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] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Vein: The vein accompanying the femoral artery in the same sheath; it is a continuation of the popliteal vein and becomes the external iliac vein. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH]
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Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] 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] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [NIH] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH] 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] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] 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]
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Forearm: The part between the elbow and the wrist. [NIH] Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [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] 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] Fungistatic: Inhibiting the growth of fungi. [EU] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [NIH] Fuzzy Logic: Approximate, quantitative reasoning that is concerned with the linguistic ambiguity which exists in natural or synthetic language. At its core are variables such as good, bad, and young as well as modifiers such as more, less, and very. These ordinary terms represent fuzzy sets in a particular problem. Fuzzy logic plays a key role in many medical expert systems. [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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gated Blood-Pool Imaging: Radionuclide ventriculography where scintigraphic data is acquired during repeated cardiac cycles at specific times in the cycle, using an electrocardiographic synchronizer or gating device. Analysis of right ventricular function is difficult with this technique; that is best evaluated by first-pass ventriculography. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH]
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Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [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 Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an 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] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of waste products in the form of urine, or both. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH]
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Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [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] 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] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
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]
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] 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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [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] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a
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primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [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] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Haemophilus influenzae: A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. [NIH]
Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from
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fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [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 Arrest: Sudden and usually momentary cessation of the heart beat. This sudden cessation may, but not usually, lead to death, sudden, cardiac. [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 Sounds: The sounds heard over the cardiac region produced by the functioning of the heart. There are four distinct sounds: the first occurs at the beginning of systole and is heard as a "lubb" sound; the second is produced by the closing of the aortic and pulmonary valves and is heard as a "dupp" sound; the third is produced by vibrations of the ventricular walls when suddenly distended by the rush of blood from the atria; and the fourth is produced by atrial contraction and ventricular filling but is rarely audible in the normal heart. The physiological concept of heart sounds is differentiated from the pathological heart murmurs. [NIH]
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] Heartbeat: One complete contraction of the heart. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] 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] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH]
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Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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]
Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatorenal Syndrome: Renal failure in those with liver disease, usually liver cirrhosis or obstructive jaundice. Historically called Heyd disease, urohepatic syndrome, or bile nephrosis. [NIH] 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] 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]
Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Hibernation: The dormant state in which some animal species pass the winter. It is
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characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. It is a natural physiological process in many warm-blooded animals. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] 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] 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 Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Hospice: Institution dedicated to caring for the terminally ill. [NIH] Hospital Units: Those areas of the hospital organization not considered departments which provide specialized patient care. They include various hospital special care wards. [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] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [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
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hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] 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] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] 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] Hypertension, Portal: Abnormally increased pressure in the portal venous system; frequently seen in cirrhosis of the liver and in other conditions which cause obstruction of the portal vein. [NIH] Hypertension, Renal: Hypertension due to renal diseases, especially chronic parenchymal disease. Hypertension as a result of compression or obstruction of the renal artery or its branches is hypertension, renovascular. [NIH] Hypertension, Renovascular: Hypertension due to compression or obstruction of the renal artery or its branches. [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] Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately,
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convulsions and coma. [EU] 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] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] 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] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoventilation: A reduction in the amount of air entering the pulmonary alveoli. [NIH] 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] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Iliac Vein: A vein on either side of the body which is formed by the union of the external and internal iliac veins and passes upward to join with its fellow of the opposite side to form the inferior vena cava. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [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]
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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] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In 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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic
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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]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate 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] In-line: A sexually-reproducing population derived from a common parentage. [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] 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] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH]
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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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-15: Cytokine that stimulates the proliferation of T-lymphocytes and shares biological activities with IL-2. IL-15 also can induce B-lymphocyte proliferation and differentiation. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [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] 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]
Investigative Techniques: Investigative techniques used in pre-clinical and clinical research, epidemiology, chemistry, immunology, genetics, etc. They do not include techniques specifically applied to diagnosis; therapeutics; anesthesia and analgesia, surgery, operative, and dentistry. [NIH]
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Involuntary: Reaction occurring without intention or volition. [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] 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isozymes: The multiple forms of a single enzyme. [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]
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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 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] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] 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]
LDL: 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] Left ventricular assist device: A mechanical device used to increase the heart's pumping ability. [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]
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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] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] 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] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [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] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] 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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH]
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Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver 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] 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] Lockjaw: Inability to open the mouth due to tonic contracture of the muscles of the jaw. [NIH]
Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [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] 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] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph
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nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [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] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] 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] 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]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [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] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that
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information centrally in the nervous system. Mechanoreceptors include hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with nonneural accessory structures. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [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] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental 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 Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
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Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolic therapy: Treatment to correct changes in metabolism that can be caused by disease. [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] 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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] 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] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH]
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Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [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] 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] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [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] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [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] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant
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feature. [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] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] 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] 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 Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardial Contraction: Contractile activity of the heart. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is
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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] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [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] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU]
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Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephrolithiasis: Kidney stones. [NIH] Nephrologist: A doctor who treats patients with kidney problems or hypertension. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] 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] Neuregulin-1: A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor. It is a ligand for the erbB-3 receptor and the erbB-4 receptor. Variant forms of neuregulin-1 occur through alternative splicing of its mRNA. [NIH]
Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] 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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH]
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Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [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] 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] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nocturia: Excessive urination at night. [EU] Nodose: Having nodes or projections. [EU] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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
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the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] N-terminal: Peptide of the area containing the NH2 group. [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] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [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] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator
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gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [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]
Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteopathic Medicine: A system of therapy and medicine based on the theory that the normal body is a vital mechanical organism whose structural and functional states are of equal importance and is capable of making its own remedies against infections and toxic conditions when there are favorable environmental circumstances and adequate nutrition. [NIH]
Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [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] Overactive bladder: A condition in which the patient experiences two or all three of the following conditions: [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the
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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] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Oxypurinol: A xanthine oxidase inhibitor. [NIH] 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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Paralysis: Loss of ability to move all or part of the body. [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] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] 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
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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 Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [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] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillinase: A beta-lactamase preferentially cleaving penicillins. (Dorland, 28th ed) EC 3.5.2.-. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral 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
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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] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH]
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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 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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [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] Phosphoprotein Phosphatase: A group of enzymes removing the serine- or threoninebound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) EC 3.1.3.16. [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] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH]
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Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] 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] 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 protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [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
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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]
Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [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] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] 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] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Popliteal Vein: The vein formed by the union of the anterior and posterior tibial veins; it courses through the popliteal space and becomes the femoral vein. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the
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splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: 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] Power Sources: Devices that supply energy. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] 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] 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]
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Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pregnancy in Diabetics: Previously diagnosed diabetics that become pregnant. This does not include either symptomatic diabetes or impaired glucose tolerance induced by pregnancy but resolved at the end of pregnancy (diabetes, gestational). [NIH] Preload: The tension in the heart muscle at the end of diastole (before the contraction). [EU] Premarin: A hormone replacement therapy drug developed by AHP (USA). [NIH] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] 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] 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] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propulsive: Tending or having power to propel; driving onward or forward; impelling to
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action or motion. [EU] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein 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 Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [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
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recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances
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primarily by verbal or nonverbal communication. [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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Alveoli: Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary congestion: Fluid accumulation in the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Valve: A valve situated at the entrance to the pulmonary trunk from the right ventricle. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulsatile Flow: Rhythmic, intermittent propagation of a fluid through a vessel or piping system, in contrast to constant, smooth propagation, which produces laminar flow. The quality of blood flow, whether smooth (laminar) or pulsatile, is important to the integrity of the tissues being artificially perfused by various heart assist devices or in regional perfusion. [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] Purgative: 1. Cathartic (def. 1); causing evacuation of the bowels. 2. A cathartic, particularly one that stimulates peristaltic action. [EU] 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] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] 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
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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] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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 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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego
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function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known. [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] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH]
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Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal Osteodystrophy: Decalcification of bone due to hyperparathyroidism secondary to chronic kidney disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [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] 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] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Residential Facilities: Long-term care facilities which provide supervision and assistance in activities of daily living with medical and nursing services when required. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration
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(= cell respiration). [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] 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] 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] Rheumatic Heart Disease: Disease of the heart resulting from rheumatic fever and characterized by inflammatory changes in the myocardium or scarring of the valves. [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] 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] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of
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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] Ryanodine: Insecticidal alkaloid isolated from Ryania speciosa; proposed as a myocardial depressant. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] 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] 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] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] 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] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] 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] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in
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response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Secular trends: A relatively long-term trend in a community or country. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [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] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] 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
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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] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [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] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sexual Abstinence: Refraining from sexual intercourse. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Siderosis: The deposition of iron in a tissue. In the eye, the iron may be deposited in the stroma adjacent to the Descemet's membrane. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet
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activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] 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 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] Smoke Inhalation Injury: Pulmonary injury following the breathing in of toxic smoke from burning materials such as plastics, synthetics, building materials, etc. This injury is the most frequent cause of death in burn patients. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [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 Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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,
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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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] 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 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] Spirochete: Lyme disease. [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] Splint: A rigid appliance used for the immobilization of a part or for the correction of deformity. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU]
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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. [NIH]
Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [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] 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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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] Stroma: The middle, thickest layer of tissue in the cornea. [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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submitochondrial Particles: The various filaments, granules, tubules or other inclusions within mitochondria. [NIH]
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Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] 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] 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] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] 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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between
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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] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] 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] Systolic pressure: The highest pressure to which blood pressure rises with the contraction of the ventricles. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tamponade: The inserting of a tampon; a dressing is inserted firmly into a wound or body cavity, as the nose, uterus or vagina, principally for stopping hemorrhage. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [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] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH]
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Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [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] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased 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] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [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] 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] 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]
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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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotoxicosis: The clinical syndrome that reflects the response of the peripheral tissues to an excess of thyroid hormone. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [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]
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Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Tricyclic: Containing three fused rings or closed chains in the molecular structure. [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] 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] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] 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]
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Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urinate: To release urine from the bladder to the outside. [NIH]
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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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varicella: Chicken pox. [EU] 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] 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] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]
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Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] 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] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] 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] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]
Ventricular Pressure: The pressure within a cardiac ventricle. Ventricular pressure waveforms can be measured in the beating heart by catheterization or estimated using imaging techniques (e.g., Doppler echocardiography). The information is useful in evaluating the function of the myocardium, cardiac valves, and pericardium, particularly with simultaneous measurement of other (e.g., aortic or atrial) pressures. [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] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH]
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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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [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] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [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]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border 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] 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]
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X-ray tube: Evacuated vessel for the production of X-radiation by the bombardment of a target, contained in an anode, with electrons accelerated by an electric field. [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] 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]
403
INDEX 3 3-dimensional, 14, 309 A Abdomen, 211, 304, 309, 321, 360, 373, 390, 391, 394, 398, 400 Abdominal, 309, 310, 328, 371, 373, 384, 396 Abdominal Pain, 309, 373 Aberrant, 61, 309 Ablation, 43, 309 Abscess, 309, 387 Acatalasia, 309, 325 Acceptor, 309, 359, 371 ACE, 5, 26, 29, 62, 84, 121, 201, 219, 222, 223, 256, 260, 309 Acetaminophen, 235, 309 Acetylcholine, 226, 309, 368 Acidosis, 236, 309, 335 Acoustic, 189, 309 Actin, 35, 46, 59, 206, 309, 346, 365, 366, 396 Action Potentials, 20, 36, 309 Activities of Daily Living, 22, 309, 384 Actomyosin, 10, 309 Acute renal, 236, 310, 350 Acyl, 49, 193, 205, 225, 310 Adaptability, 215, 310, 326 Adaptation, 31, 58, 310 Adenine, 310, 381 Adenosine, 32, 202, 226, 310, 313, 317, 322, 353, 374 Adenovirus, 8, 131, 310 Adipocytes, 310, 359 Adjunctive Therapy, 198, 310 Adjustment, 5, 29, 135, 236, 310 Adjuvant, 152, 310, 345 Adjuvant Therapy, 152, 310 Adrenal Cortex, 310, 312, 332, 378, 384 Adrenal Glands, 310, 313, 384 Adrenal insufficiency, 232, 235, 310 Adrenal Medulla, 310, 325, 340, 341, 368 Adrenaline, 151, 310 Adrenergic Agents, 194, 310 Adrenergic Agonists, 194, 218, 310 Adrenergic Antagonists, 194, 311 Adverse Effect, 70, 311, 388 Aerobic, 134, 166, 167, 311, 342, 364 Afferent, 26, 61, 115, 311, 359, 375
Affinity, 10, 63, 311, 359, 363, 389 Afterload, 176, 311, 332 Agar, 311, 375 Age Groups, 40, 41, 311 Age of Onset, 311, 397 Aged, 80 and Over, 311 Agonist, 9, 44, 195, 203, 209, 223, 311, 334, 337 Airway, 76, 183, 184, 232, 311, 389 Airway Obstruction, 232, 311 Akinesia, 60, 311 Albumin, 4, 5, 311, 363, 375 Albuminuria, 5, 311 Aldehydes, 312, 400 Aldosterone, 68, 79, 90, 106, 110, 114, 119, 176, 188, 202, 203, 219, 312 Aldosterone Antagonists, 114, 312 Alendronate, 209, 312 Alertness, 302, 312, 322 Algorithms, 41, 312, 320 Alimentary, 312, 356 Alkaline, 309, 312, 313, 323 Alkaloid, 312, 319, 328, 386 Alkalosis, 194, 236, 312 Alleles, 26, 312, 350 Allergen, 312, 334 Allopurinol, 47, 65, 67, 312 Alpha Particles, 312, 381 Alpha-1, 84, 203, 312, 377 Alprenolol, 312, 363 Alternative medicine, 257, 312 Alternative Splicing, 312, 367 Ameliorating, 224, 225, 312 Amine, 313, 351 Amino Acid Sequence, 313, 315, 346 Amino Acids, 141, 226, 229, 313, 314, 346, 363, 372, 376, 380, 385, 388, 396, 397 Amiodarone, 162, 176, 219, 313 Ammonia, 313, 397 Amphetamine, 313 Amrinone, 218, 313 Amyloidosis, 139, 236, 313 Anaerobic, 313, 348 Anaesthesia, 313, 354 Anal, 66, 286, 313, 365 Analgesic, 236, 309, 313 Analogous, 51, 59, 313, 396 Analytes, 280, 314
404 Heart Failure
Anaphylatoxins, 314, 329 Anaphylaxis, 204, 314 Anatomical, 314, 317, 321, 330, 336, 354, 386 Anemia, 69, 104, 109, 114, 155, 176, 216, 232, 284, 285, 301, 314, 328, 344, 394 Anesthesia, 185, 204, 237, 311, 314, 339, 356, 378 Anesthetics, 314, 318, 341 Aneurysm, 314, 398 Angina Pectoris, 119, 183, 205, 206, 216, 218, 225, 228, 232, 234, 314, 321, 363 Anginal, 312, 314, 315, 368 Angiogenesis, 220, 314, 361 Angioplasty, 234, 314, 366 Angiotensin converting enzyme inhibitor, 69, 170, 171, 222, 314 Angiotensin-Converting Enzyme Inhibitors, 71, 77, 91, 106, 108, 109, 233, 314 Angiotensinogen, 219, 314, 384 Animal model, 7, 11, 30, 31, 47, 48, 52, 53, 55, 59, 61, 62, 124, 129, 163, 247, 314 Anions, 311, 315, 357, 388, 392 Ankle, 6, 315 Anode, 315, 401 Anorexia, 216, 225, 315 Antagonism, 90, 125, 154, 315, 322, 336 Antecedent, 84, 315 Anthracycline, 192, 315, 333 Anthranilic Acids, 201, 315 Antianginal, 313, 315 Antiarrhythmic, 23, 245, 313, 315 Antibacterial, 315, 390 Antibiotic, 315, 333, 337, 372, 390, 394 Antibodies, 13, 64, 315, 348, 350, 353, 361, 364, 375 Antibody, 46, 221, 311, 315, 321, 329, 348, 351, 353, 354, 362, 364, 382, 388, 390 Anticholinergic, 315, 336 Anticoagulant, 315, 379 Antidiuretic, 315, 367 Antigen, 311, 314, 315, 329, 346, 351, 352, 353, 354, 362, 388 Antigen-Antibody Complex, 315, 329 Antihypertensive, 237, 245, 312, 316, 351 Anti-inflammatory, 69, 176, 309, 316, 317, 354 Anti-Inflammatory Agents, 316, 317 Antimetabolite, 316, 334 Antineoplastic, 316, 337, 346
Antioxidant, 42, 45, 46, 47, 48, 49, 316, 317, 371 Antipyretic, 309, 316 Antiviral, 316, 334, 372 Anuria, 316, 358 Anus, 313, 316, 321, 356 Anxiety, 199, 216, 225, 316 Anxiety Disorders, 199, 316 Aorta, 185, 188, 224, 316, 324, 331, 349, 378, 384, 399 Aortic Coarctation, 132, 316 Aortic Valve, 185, 316 Apnea, 17, 184, 187, 316 Apoptosis, 8, 11, 13, 43, 45, 46, 52, 53, 59, 92, 316, 325 Applicability, 195, 316 Aqueous, 316, 319, 333, 351 Arachidonic Acid, 25, 316, 359, 379 Arginine, 127, 141, 142, 178, 314, 316, 368 Aromatic, 177, 316, 363, 374 Arrestin, 195, 316 Arrhythmia, 74, 140, 162, 165, 200, 219, 220, 228, 234, 259, 280, 315, 317, 344, 399 Arteriolar, 317, 322, 384 Arterioles, 43, 224, 317, 321, 323, 363, 365, 398 Arteriosclerosis, 317, 352 Arteriosus, 317, 381 Arteriovenous, 56, 76, 90, 317, 363 Arteriovenous Fistula, 76, 90, 317 Ascites, 203, 235, 317 Ascorbic Acid, 120, 204, 317, 352 Aspirin, 70, 81, 84, 106, 108, 169, 234, 256, 317 Assay, 14, 34, 45, 46, 317, 353 Asymptomatic, 91, 156, 162, 248, 284, 309, 317, 344 ATP, 18, 49, 206, 218, 317, 332, 337, 346, 347, 350, 374, 380 Atrial, 13, 16, 26, 46, 93, 132, 147, 188, 193, 218, 220, 221, 222, 254, 313, 317, 344, 349, 399 Atrial Fibrillation, 16, 93, 132, 218, 220, 317 Atrial Flutter, 218, 317 Atrioventricular, 221, 317, 392 Atrioventricular Node, 317, 392 Atrium, 185, 193, 221, 222, 317, 324, 364, 392, 399 Atrophy, 56, 318, 367 Attenuated, 92, 214, 318, 336 Attenuation, 24, 43, 209, 214, 318
Index 405
Auditory, 318, 348, 361, 398 Autacoids, 318, 354 Autoimmune disease, 194, 318, 365 Autoimmune Hepatitis, 235, 318 Autoimmunity, 216, 318 Autologous, 11, 138, 156, 163, 179, 318 Autonomic, 30, 61, 130, 167, 188, 198, 199, 247, 255, 309, 318, 368, 372, 389, 392 Autonomic Nervous System, 188, 318, 372, 389, 392 Autonomic Neuropathy, 247, 318 B Bacteria, 310, 315, 318, 320, 339, 340, 343, 348, 350, 363, 382, 385, 387, 390, 396, 397, 398 Bacterial Physiology, 310, 318 Bactericidal, 318, 342 Bacteriophage, 318, 375, 396 Bacterium, 318, 350 Bacteriuria, 318, 397 Barbiturate, 318, 394 Baroreflex, 124, 136, 319 Basal Ganglia, 319 Basal Ganglia Diseases, 319 Base, 116, 171, 184, 310, 312, 319, 334, 342, 346, 348, 357, 358, 393 Basement Membrane, 319, 342 Basophils, 319, 326, 348, 359 Beer, 319, 324 Benign, 71, 216, 225, 260, 319, 348, 366 Benign prostatic hyperplasia, 260, 319 Benzamides, 201, 319 Benzoic Acid, 201, 319 Benzyl Alcohol, 201, 319 Berberine, 81, 319 Beta blocker, 71, 95, 176, 233, 260, 319 Bilateral, 319, 396 Bile, 235, 319, 320, 327, 345, 350, 357, 360, 378, 391 Bile Acids, 319, 320, 391 Bile Acids and Salts, 319, 320 Bile Ducts, 235, 320, 345, 378 Bile Pigments, 320, 357 Biliary, 235, 320 Biliary Tract, 235, 320 Bilirubin, 311, 320, 345, 352 Bioavailability, 24, 44, 48, 179, 203, 320 Biochemical Phenomena, 320 Biological Phenomena, 57, 320 Biological therapy, 320, 348 Biomarkers, 68, 83, 160, 320 Biophysics, 48, 55, 64, 115, 320
Biopsy, 56, 284, 320, 372 Biosynthesis, 312, 316, 320, 374, 388, 398 Biotechnology, 67, 245, 257, 275, 320 Biotypes, 320, 348 Bisoprolol, 98, 320 Bivalent, 321, 363 Bladder, 237, 260, 318, 319, 321, 332, 365, 367, 379, 384, 397, 398 Blood Coagulation, 321, 323, 394 Blood Glucose, 236, 237, 287, 288, 321, 350, 353, 356 Blood Platelets, 321, 388, 394 Blood Volume, 10, 207, 321 Blot, 14, 46, 321, 353 Blotting, Western, 321, 353 Body Fluids, 258, 312, 320, 321, 322, 338, 389, 396 Body Mass Index, 321, 370 Body Regions, 321, 328 Body Temperature Regulation, 208, 321 Bolus, 129, 321 Bolus infusion, 321 Bone Marrow, 11, 138, 321, 360, 361, 364, 365, 389 Bone scan, 321, 386 Bowel, 216, 313, 321, 335, 340, 358, 373 Bowel Movement, 321, 335 Bradykinin, 62, 117, 170, 171, 321, 357, 368, 375 Branch, 72, 110, 170, 171, 198, 221, 299, 322, 339, 346, 361, 370, 371, 381, 384, 390, 394 Breakdown, 56, 322, 335, 345 Breeding, 41, 322 Bronchi, 322, 341, 362, 395 Bronchial, 322, 351 Bronchiseptica, 322, 373 Bronchitis, 322, 327 Buffers, 319, 322 Bulimia, 216, 225, 322 Bypass, 60, 127, 159, 234, 322, 366 C Cachexia, 87, 133, 209, 216, 322 Caffeine, 233, 322, 381 Calcification, 214, 317, 322 Calcineurin, 34, 58, 322 Calcium channel blocker, 115, 176, 260, 289, 323, 399 Calcium Channel Blockers, 176, 260, 289, 323 Calmodulin, 322, 323, 355
406 Heart Failure
Capillary, 51, 69, 224, 313, 322, 323, 381, 399 Capillary Permeability, 322, 323 Capsules, 323, 337, 345 Captopril, 142, 250, 254, 323 Carbenicillin, 176, 323 Carbohydrate, 18, 49, 323, 347 Carbon Dioxide, 323, 327, 333, 345, 352, 375, 384, 399 Carboxy, 179, 225, 228, 323 Carcinogenic, 323, 355, 378, 391 Carcinogens, 323, 369 Cardiac arrest, 78, 100, 200, 232, 323, 392 Cardiac Glycosides, 142, 194, 324 Cardiogenic, 248, 324 Cardiomegaly, 324 Cardiomyopathy, Alcoholic, 224, 324 Cardiomyoplasty, 179, 324 Cardiopulmonary, 51, 67, 167, 168, 188, 232, 324 Cardiopulmonary Bypass, 51, 324 Cardiopulmonary Resuscitation, 232, 324 Cardioselective, 320, 324 Cardiotonic, 313, 324, 336, 337 Cardiotoxic, 192, 324 Cardiovascular disease, 8, 17, 25, 28, 30, 34, 38, 44, 52, 61, 118, 196, 203, 214, 216, 223, 229, 238, 247, 288, 324 Cardiovascular System, 47, 219, 318, 324 Carnitine, 49, 121, 324 Carotene, 325, 385 Carotid Arteries, 224, 325 Case report, 76, 325, 328 Case series, 325, 328 Caspase, 46, 92, 325 Catalase, 48, 309, 325 Catecholamine, 8, 83, 204, 325, 334, 337, 374 Catheterization, 154, 305, 314, 325, 356, 366, 399 Catheters, 228, 325 Causal, 62, 259, 325, 350, 394 Causality, 59, 325 Cause of Death, 31, 44, 183, 194, 196, 232, 325, 333, 389 Caveolae, 57, 325 Caveolins, 325 Cell Adhesion, 45, 325 Cell Death, 24, 39, 43, 46, 48, 192, 316, 325, 346, 366 Cell Degranulation, 15, 326 Cell Differentiation, 216, 326, 388
Cell Division, 318, 326, 348, 364, 375 Cell Fusion, 60, 326 Cell membrane, 233, 323, 325, 326, 334, 342, 355, 374, 377, 383, 389, 400 Cell Membrane Structures, 325, 326 Cell proliferation, 216, 317, 326, 388 Cell Respiration, 326, 364, 384 Cell Survival, 326, 348 Cell Transplantation, 138, 326 Cellulose, 326, 375 Cerebral, 125, 211, 228, 319, 326, 334, 341, 342, 380, 393 Cerebrovascular, 54, 224, 232, 319, 323, 324, 326 Cerebrum, 326 Cervical, 326 Character, 314, 326, 333 Chemokines, 11, 326 Chemoreceptors, 188, 326 Chemotactic Factors, 327, 329 Chemotherapy, 176, 310, 327 Chest Pain, 183, 232, 234, 287, 327 Cholangitis, 235, 327 Cholecystitis, 235, 327 Cholecystokinin, 212, 327 Cholelithiasis, 235, 327 Chromatin, 316, 327, 341, 368 Chromosomal, 327, 393 Chromosome, 327, 348, 350, 359, 393 Chronic Disease, 40, 187, 189, 216, 246, 285, 322, 327 Chronic Obstructive Pulmonary Disease, 184, 204, 327 Chronic renal, 114, 227, 232, 235, 236, 237, 327, 345, 376 Chronotropic, 104, 327 Circulatory system, 227, 327, 339 CIS, 9, 12, 14, 50, 327, 385 Citric Acid, 49, 327 Citric Acid Cycle, 49, 327 Citrus, 317, 327, 328 Clamp, 30, 37, 328 Clear cell carcinoma, 328, 334 Cleave, 62, 328 Clinical Medicine, 328, 377 Clinical study, 126, 156, 328, 331 Cloning, 320, 328, 359 Coagulation, 321, 328, 350, 375, 395 Cobalt, 324, 328 Coca, 328 Cocaine, 176, 328 Coenzyme, 143, 317, 328
Index 407
Cofactor, 328, 379, 394 Colic, 204, 328 Collagen, 15, 62, 319, 328, 343, 344, 345, 361, 375, 378 Collapse, 184, 314, 322, 329, 389 Colloidal, 311, 329, 339, 388 Combination Therapy, 202, 236, 329, 341 Combinatorial, 63, 329 Comorbidity, 93, 98, 101, 126, 329 Complement, 11, 204, 314, 329, 375 Complementary and alternative medicine, 123, 146, 329 Complementary medicine, 123, 329 Complete remission, 329, 384 Computational Biology, 275, 330 Computed tomography, 136, 214, 330, 386 Computerized axial tomography, 330, 386 Computerized tomography, 330 Concomitant, 11, 23, 46, 56, 77, 152, 209, 257, 330 Condoms, 286, 330 Conduction, 74, 188, 221, 317, 330 Cones, 330, 375, 385 Confusion, 330, 336, 352, 397 Congestion, 176, 186, 203, 207, 330 Conjugated, 44, 319, 320, 330, 332, 366 Connective Tissue, 317, 321, 328, 330, 344, 345, 360, 363, 385, 393 Consciousness, 232, 313, 330, 334, 337, 350, 393 Constipation, 140, 250, 258, 330, 373 Constriction, 227, 330, 357, 398 Constriction, Pathologic, 330, 398 Consumption, 18, 167, 233, 286, 306, 330, 334, 371 Continuum, 57, 330 Contractile Proteins, 63, 225, 330 Contracture, 331, 360 Contraindications, ii, 331 Control group, 6, 16, 28, 56, 152, 167, 168, 171, 259, 331, 378, 382 Controlled clinical trial, 67, 123, 124, 153, 167, 331 Controlled study, 125, 331 Conus, 331, 381 Conventional therapy, 331 Conventional treatment, 162, 331 Coordination, 331, 365 Coronary Angiography, 234, 331 Coronary Arteriosclerosis, 331, 365 Coronary Artery Bypass, 20, 91, 331 Coronary Circulation, 19, 51, 314, 331
Coronary Disease, 91, 159, 160, 169, 280, 331 Coronary heart disease, 40, 159, 169, 205, 286, 288, 324, 331 Coronary Thrombosis, 331, 363, 365 Coronary Vessels, 331 Corpus, 331, 332, 372, 378, 388 Corpus Luteum, 332, 378 Cortex, 332, 342 Cortical, 203, 332, 342, 387 Cortisol, 311, 332 Counterpulsation, 124, 332 Cranial, 332, 348, 372, 398 Creatine, 18, 57, 121, 148, 183, 332 Creatine Kinase, 18, 57, 148, 183, 332 Creatinine, 5, 6, 112, 237, 258, 304, 332, 358 Criterion, 23, 332 Cultured cells, 58, 332 Curative, 332, 368, 394 Cutaneous, 37, 237, 332, 360, 375 Cyclic, 76, 322, 323, 332, 348, 368, 374, 375, 376, 379, 387 Cysteine, 226, 326, 332 Cystine, 332 Cystitis, 204, 332 Cytochrome, 13, 46, 332, 371 Cytokine, 31, 60, 118, 332, 356, 394 Cytomegalovirus, 226, 333 Cytopenia, 216, 333 Cytoplasm, 47, 316, 319, 326, 330, 333, 341, 348, 355, 363, 364, 368, 385, 386 Cytoskeletal Proteins, 59, 333 Cytoskeleton, 333 Cytotoxic, 333, 356, 388 D Dairy Products, 333, 386 Data Collection, 40, 166, 208, 333, 344 Databases, Bibliographic, 275, 333 Daunorubicin, 333, 337 Deamination, 333, 397 Death Certificates, 40, 333 Decarboxylation, 333, 351, 398 Decompensation, 19, 24, 43, 58, 153, 333 Defibrillation, 14, 333 Degenerative, 8, 331, 333, 350, 365, 385 Dehydration, 250, 333 Deletion, 35, 43, 53, 316, 333 Delirium, 216, 225, 333 Delusions, 334, 380 Dementia, 211, 212, 216, 225, 250, 286, 334 Dendrites, 334, 367
408 Heart Failure
Density, 15, 64, 209, 321, 334, 338, 360, 369, 390 Deoxyglucose, 128, 334 Depolarization, 36, 193, 334, 336, 388 Depressive Disorder, 54, 334, 360 Dermatitis, 216, 334 DES, 200, 314, 334 Desensitization, 194, 195, 334 Desmin, 59, 61, 334 Deuterium, 334, 351 Developed Countries, 66, 334 Dexfenfluramine, 259, 334 DHEA, 143, 334 Diabetes Insipidus, 223, 334 Diabetes Mellitus, 46, 130, 140, 160, 232, 236, 238, 335, 347, 350 Diabetes, Gestational, 236, 335, 378 Diabetic Foot, 238, 335 Diabetic Ketoacidosis, 236, 335 Diabetic Retinopathy, 205, 218, 335 Diagnostic Imaging, 214, 335 Diagnostic procedure, 175, 257, 335, 374 Dialyzer, 335, 349 Diarrhea, 258, 302, 335 Diastole, 176, 179, 185, 335, 378 Diastolic, 16, 35, 48, 51, 77, 79, 82, 91, 93, 105, 123, 147, 149, 162, 163, 176, 179, 206, 210, 213, 214, 218, 232, 243, 248, 250, 286, 332, 335, 352 Diastolic heart failure, 77, 82, 91, 93, 162, 335 Diastolic pressure, 213, 286, 332, 335, 352 Dietitian, 4, 335 Diffusion, 323, 335, 336, 355, 397 Digestion, 223, 312, 319, 320, 321, 335, 360, 391 Digestive system, 173, 335 Digestive tract, 318, 335, 389 Digitalis, 4, 16, 126, 137, 165, 218, 324, 336 Dihydrotestosterone, 336, 383 Dilatation, 15, 35, 53, 62, 155, 176, 185, 210, 314, 336, 378, 398, 399 Dilatation, Pathologic, 336, 398 Dilate, 213, 336 Dilation, 8, 34, 43, 191, 213, 322, 336, 398 Diltiazem, 176, 336 Dilution, 336, 341, 375 Diphtheria, 288, 336 Diploid, 336, 375 Direct, iii, 16, 19, 38, 47, 48, 57, 65, 129, 171, 176, 233, 263, 287, 328, 336, 337, 351, 383, 392
Disease Progression, 4, 48, 336 Disease Vectors, 336, 355 Disinfectant, 336, 342 Disopyramide, 176, 336 Disorientation, 330, 334, 336 Dissection, 336, 396 Dissociation, 116, 311, 336, 357 Distal, 203, 208, 222, 331, 337, 339, 357, 380 Diuresis, 322, 337 Diuretic, 78, 114, 149, 188, 189, 219, 337, 345, 390 Diuretics, Thiazide, 114, 265, 337 DNA Topoisomerase, 337, 346 Dobutamine, 20, 79, 218, 337 Dopamine, 218, 226, 313, 328, 337, 374 Dorsal, 37, 337, 377, 390 Dorsum, 337 Dosage Forms, 181, 337 Dose-dependent, 66, 337 Doxorubicin, 176, 337 Drive, ii, vi, 4, 32, 33, 113, 198, 199, 231, 232, 234, 235, 236, 337 Drug Interactions, 268, 337 Drug Resistance, 233, 337, 338 Drug Tolerance, 337, 338, 395 Duct, 325, 327, 338, 342, 386 Duke, 54, 116, 195, 338 Duodenum, 319, 338, 391 Dura mater, 338, 362, 371 Dwarfism, 209, 338 Dynorphins, 338, 383 Dyskinesia, 338 Dyslipidemia, 237, 238, 338 Dyspareunia, 338, 341 Dysphoric, 334, 338 Dysplasia, 59, 338 Dyspnea, 135, 137, 162, 167, 225, 324, 333, 338 E Echocardiography, 13, 20, 48, 50, 60, 77, 79, 115, 137, 158, 338, 399 Ectopic, 14, 338 Effector, 226, 309, 329, 338, 368, 374 Effector cell, 338, 368 Ejection fraction, 4, 16, 60, 66, 71, 80, 93, 94, 97, 100, 159, 191, 338 Elastin, 328, 338, 343 Elective, 135, 339 Electric shock, 324, 333, 339 Electrocardiogram, 158, 339 Electrode, 192, 221, 222, 315, 339
Index 409
Electrolyte, 116, 194, 219, 223, 236, 237, 312, 334, 339, 350, 358, 377, 389 Electrons, 316, 319, 339, 357, 361, 371, 381, 401 Electrophoresis, 64, 339 Electrophysiological, 20, 65, 81, 229, 339, 399 Elementary Particles, 339, 361, 368, 380 Embolus, 339, 354 Embryo, 326, 339, 354 Emphysema, 250, 327, 339 Empirical, 153, 339 Endarterectomy, 314, 339 Endocarditis, 176, 232, 235, 339 Endocardium, 339 Endocrine System, 339, 367 Endocytosis, 325, 339 Endorphins, 340, 383 Endothelial cell, 24, 42, 43, 45, 221, 229, 339, 340, 394 Endothelium, 24, 37, 110, 170, 171, 340, 368 Endothelium, Lymphatic, 340 Endothelium, Vascular, 340 Endothelium-derived, 24, 340, 368 Endotoxic, 340, 359 Endotoxin, 340, 397 End-stage renal, 3, 232, 327, 340, 376 Energetic, 47, 340 Energy balance, 16, 340, 359 Enhancer, 33, 340 Enkephalins, 340, 383 Enoximone, 152, 153, 340 Enterocolitis, 66, 340 Environmental Exposure, 340, 369 Environmental Health, 274, 276, 340 Enzymatic, 46, 183, 200, 323, 325, 329, 340, 344, 351, 385 Enzyme, 5, 14, 33, 47, 48, 50, 65, 70, 80, 82, 117, 121, 128, 177, 178, 200, 201, 203, 211, 215, 219, 222, 255, 260, 264, 309, 325, 328, 337, 338, 340, 341, 347, 348, 350, 354, 357, 359, 360, 363, 366, 374, 375, 376, 379, 380, 382, 383, 384, 388, 392, 394, 400, 401 Enzyme Inhibitors, 80, 341, 375 Eosinophils, 326, 341, 348, 359 Epidemic, 16, 55, 238, 341, 390 Epidemiological, 4, 29, 40, 232, 247, 341 Epidermal, 192, 341 Epidermal Growth Factor, 192, 341 Epidermis, 341
Epinephrine, 219, 310, 311, 337, 341, 368, 397 Epithelial, 37, 203, 341, 350 Epithelial Cells, 203, 341, 350 Epithelium, 319, 340, 341 Erectile, 205, 237, 341, 372 Erection, 341 Ergometer, 167, 341 Erythrocyte Volume, 321, 341 Erythrocytes, 314, 321, 341, 350, 383 Esophagus, 335, 336, 341, 362, 374, 383, 391 Estrogen, 9, 166, 209, 234, 260, 341 Estrogen Replacement Therapy, 234, 341 Ethanol, 176, 341 Eukaryotic Cells, 333, 342, 354, 370, 397 Evacuation, 330, 342, 358, 381 Evoke, 32, 152, 342, 391 Excipients, 197, 342 Excitability, 59, 342, 366 Excitation, 7, 23, 27, 30, 38, 64, 317, 342 Excitatory, 199, 342, 347 Excrete, 316, 342, 358 Exercise Test, 75, 158, 168, 342 Exercise Tolerance, 18, 38, 84, 104, 137, 160, 162, 342 Exhaustion, 315, 342 Exocrine, 327, 342, 371 Exocytosis, 326, 342 Exogenous, 48, 55, 209, 323, 342, 397 Expert Systems, 342, 345 Expiration, 184, 342, 384 Expiratory, 184, 342 Extensor, 342, 380 Extracellular Matrix, 15, 33, 35, 62, 107, 219, 330, 342, 343, 344, 361 Extracellular Matrix Proteins, 343, 361 Extracellular Space, 233, 342, 343, 363 Extracorporeal, 10, 36, 228, 343, 350 Extracorporeal Membrane Oxygenation, 10, 343 Extraction, 285, 343 Extrapyramidal, 337, 343 Extremity, 237, 343, 386 Eye Infections, 310, 343 F Family Planning, 275, 343 Family Practice, 79, 88, 91, 112, 131, 139, 285, 343 Fatigue, 6, 22, 25, 39, 61, 82, 167, 186, 187, 197, 225, 258, 284, 302, 343, 349
410 Heart Failure
Fatty acids, 18, 19, 49, 50, 209, 311, 335, 343, 379, 394 Fatty Liver, 235, 343 Feces, 330, 343 Femoral, 208, 224, 324, 343, 376 Femoral Artery, 324, 343 Femoral Vein, 208, 343, 376 Femur, 343 Fenfluramine, 259, 334, 343 Ferritin, 284, 344 Fibrillation, 182, 333, 344 Fibrin, 321, 344, 373, 394, 395 Fibrinogen, 344, 375, 394 Fibrinolytic, 84, 344 Fibroblasts, 15, 43, 44, 49, 221, 229, 344 Fibrosis, 11, 45, 59, 195, 203, 284, 331, 344, 386 Fibula, 344, 376 Filtration, 258, 344, 358 Fistula, 15, 48, 344 Flatus, 344, 345 Flecainide, 176, 344 Fluorescence, 11, 13, 344 Focus Groups, 22, 344 Folate, 344 Fold, 65, 203, 220, 344 Folic Acid, 285, 344 Foot Ulcer, 237, 335, 344 Forearm, 32, 321, 345 Free Radical Scavengers, 25, 345 Fructose, 345, 350 Fungi, 343, 345, 348, 363, 401 Fungistatic, 319, 345 Furosemide, 85, 129, 133, 345 Fuzzy Logic, 131, 345 G Gadolinium, 37, 78, 86, 345 Gallbladder, 309, 320, 327, 335, 345 Gallstones, 320, 327, 345 Ganglia, 37, 309, 319, 345, 367, 372, 392 Gas, 184, 188, 313, 323, 335, 344, 345, 351, 368, 369, 381, 385, 392, 398, 399 Gas exchange, 345, 381, 385, 399 Gastric, 212, 323, 324, 337, 341, 345, 351 Gastric Acid, 212, 345 Gastrin, 212, 345, 351 Gastrointestinal tract, 284, 285, 341, 345, 359, 388, 396 Gated Blood-Pool Imaging, 94, 345 Gelatin, 345, 347, 394 Gelsolin, 35, 346
Gene Expression, 9, 12, 16, 17, 25, 32, 33, 45, 48, 50, 51, 53, 57, 66, 88, 116, 346 General practitioner, 21, 346 Genetic Code, 346, 369 Genetic Counseling, 236, 346 Genetic testing, 284, 346 Genetics, 55, 60, 87, 346, 356 Genistein, 9, 346 Genital, 318, 328, 346, 398 Genitourinary, 237, 346, 398 Genitourinary system, 237, 346 Genotype, 346, 374 Geriatric, 28, 29, 118, 126, 237, 346 Giant Cells, 346, 386 Ginseng, 141, 142, 145, 346 Gland, 310, 346, 360, 371, 375, 379, 387, 391, 395 Glomerular, 218, 224, 236, 346, 358, 384 Glomeruli, 346, 347 Glomerulonephritis, 218, 221, 237, 346 Glomerulosclerosis, 205, 347 Glomerulus, 346, 347, 357, 366 Glottis, 347, 373 Glucokinase, 347, 350 Glucose Intolerance, 157, 158, 335, 347 Glucose tolerance, 158, 205, 335, 347, 378 Glucose Tolerance Test, 347 Glutamic Acid, 344, 347, 378 Glutathione Peroxidase, 48, 347, 387 Glycine, 319, 320, 347, 388 Glycolysis, 13, 347 Glycoprotein, 344, 346, 347, 394, 397 Governing Board, 347, 377 Gp120, 347, 372 Graft, 91, 189, 190, 211, 347, 354, 366 Grafting, 20, 60, 234, 331, 347, 354 Gram-negative, 322, 340, 347, 348 Granulocytes, 348, 359, 388, 400 Grasses, 344, 348 Gravis, 204, 348 Growth factors, 42, 216, 226, 348 Guanidine, 336, 348 Guanylate Cyclase, 52, 348, 368 H Haemophilus, 288, 348 Haemophilus influenzae, 288, 348 Hair Cells, 348, 362 Half-Life, 19, 348 Haploid, 348, 375 Haptens, 311, 348 Headache, 302, 322, 348, 352 Health Care Costs, 348, 349
Index 411
Health Expenditures, 25, 348, 349 Health Services, 28, 29, 75, 152, 157, 164, 167, 171, 349 Health Status, 158, 349 Heart Arrest, 324, 349 Heart attack, 6, 183, 199, 214, 250, 259, 286, 287, 324, 349 Heart Catheterization, 305, 349 Heart Sounds, 301, 349 Heart Transplantation, 10, 95, 109, 125, 161, 349 Heart Valves, 193, 349 Heartbeat, 193, 198, 206, 303, 349, 392, 399 Hematuria, 236, 349 Heme, 320, 332, 349, 366, 376, 398 Hemochromatosis, 235, 259, 284, 285, 349 Hemodiafiltration, 349, 397 Hemodialysis, 4, 236, 335, 349, 350, 358, 397 Hemodynamics, 19, 35, 182, 221, 233, 254, 349 Hemofiltration, 236, 349, 350, 397 Hemoglobin, 52, 188, 314, 341, 349, 350, 357, 359, 376, 394 Hemolysis, 36, 350 Hemolytic, 236, 350, 394 Hemorrhage, 204, 348, 350, 366, 391, 393, 400 Hemostasis, 220, 350, 388 Hepatic, 235, 311, 334, 347, 350, 360, 376 Hepatic Encephalopathy, 235, 350 Hepatitis, 235, 288, 350, 399 Hepatocytes, 350 Hepatorenal Syndrome, 235, 350 Hereditary, 236, 285, 350, 365, 367, 394 Heredity, 286, 287, 346, 350 Heterogeneity, 57, 311, 350 Heterozygote, 62, 350 Hexokinase, 49, 350 Hibernation, 136, 137, 350 Histamine, 226, 314, 351 Histidine, 351 Histology, 57, 351 Homeostasis, 30, 38, 209, 351, 390 Homogeneous, 330, 351, 373 Homologous, 312, 321, 350, 351, 393 Hormonal, 26, 51, 106, 219, 318, 341, 351 Hormone Replacement Therapy, 234, 351, 378 Hormone therapy, 88, 310, 351 Hospice, 21, 117, 118, 351 Hospital Units, 76, 351
Hybrid, 351 Hybridization, 59, 326, 351 Hydralazine, 176, 266, 268, 351 Hydrogen Peroxide, 325, 347, 351, 359, 392 Hydrolysis, 206, 226, 351, 374, 376, 380 Hydrophilic, 226, 351 Hydrophobic, 226, 351, 360 Hydroxylysine, 329, 352 Hydroxyproline, 329, 352 Hyperbilirubinemia, 352, 357 Hypercholesterolemia, 124, 140, 338, 352 Hyperglycemia, 46, 205, 236, 352 Hyperlipidaemia, 205, 352 Hyperlipidemia, 232, 338, 352 Hyperlipoproteinemia, 352 Hyperplasia, 219, 352 Hypersensitivity, 312, 314, 334, 352, 359, 385 Hypertension, 4, 13, 16, 26, 30, 31, 37, 86, 90, 94, 106, 111, 115, 122, 141, 152, 160, 170, 176, 178, 181, 183, 199, 202, 203, 204, 205, 206, 212, 216, 218, 219, 220, 223, 225, 226, 227, 228, 232, 233, 234, 235, 236, 237, 238, 241, 245, 247, 250, 258, 260, 285, 286, 287, 288, 289, 314, 321, 323, 324, 348, 352, 360, 363, 367, 377 Hypertension, Portal, 235, 352 Hypertension, Renal, 202, 352 Hypertension, Renovascular, 352 Hyperthyroidism, 105, 352 Hypertriglyceridemia, 205, 338, 352 Hypertrophic cardiomyopathy, 50, 57, 218, 352 Hyperventilation, 187, 232, 352 Hypnotic, 318, 352, 394 Hypoglycaemia, 334, 352 Hypoglycemia, 237, 353 Hypoglycemic, 236, 353 Hypoglycemic Agents, 236, 353 Hypotension, 52, 91, 193, 204, 216, 225, 232, 237, 302, 353 Hypothalamic, 198, 353 Hypothalamus, 318, 353, 375 Hypothermia, 141, 190, 352, 353 Hypoventilation, 187, 353 Hypoxanthine, 353, 400 Hypoxia, 17, 33, 43, 183, 334, 353 I Id, 120, 139, 280, 282, 289, 290, 291, 298, 300, 353
412 Heart Failure
Idiopathic, 27, 43, 62, 65, 81, 87, 104, 176, 210, 224, 353, 386 Iliac Vein, 343, 353 Imaging procedures, 353, 395 Immune response, 310, 315, 318, 348, 353, 392, 399, 400 Immune system, 318, 320, 338, 353, 354, 359, 361, 365, 398, 400 Immunity, 353, 356 Immunoassay, 34, 98, 353 Immunoblotting, 13, 64, 353 Immunodeficiency, 201, 216, 286, 353 Immunofluorescence, 14, 353 Immunogenic, 353, 359 Immunoglobulin, 205, 315, 353, 364 Immunohistochemistry, 13, 57, 353 Immunologic, 327, 353, 354 Immunology, 310, 311, 354, 356 Immunophilin, 322, 354 Immunosuppressive, 322, 354 Immunotherapy, 320, 334, 354 Impairment, 48, 62, 78, 111, 187, 197, 213, 224, 334, 338, 343, 354, 362, 380 Implantation, 19, 65, 156, 163, 184, 185, 222, 354 Impotence, 284, 285, 341, 354 In situ, 13, 45, 51, 57, 354 In Situ Hybridization, 45, 57, 354 In vitro, 7, 13, 14, 18, 19, 34, 36, 37, 42, 44, 45, 47, 48, 49, 50, 53, 56, 66, 326, 354, 388 Incision, 354, 356 Incubation, 354, 373 Incubation period, 354, 373 Indicative, 189, 191, 207, 214, 238, 354, 371, 398 Indomethacin, 200, 354 Induction, 9, 11, 14, 27, 45, 50, 53, 354, 356 Infancy, 132, 354 Infant, Newborn, 311, 354 Infection Control, 232, 235, 355 Infiltration, 346, 355, 378 Infusion, 11, 129, 134, 154, 227, 355, 366 Ingestion, 347, 355, 376 Initiation, 8, 84, 168, 355, 396 Initiator, 14, 355 Inlay, 355, 385 In-line, 222, 355 Innervation, 355, 373, 386 Inositol, 226, 355, 387 Inositol 1,4,5-Trisphosphate, 226, 355 Inotropic, 21, 63, 66, 118, 176, 190, 201, 218, 313, 337, 340, 355
Inpatients, 5, 355 Insecticides, 177, 355 Insight, 24, 29, 36, 39, 40, 59, 355 Insulator, 355, 365 Insulin-dependent diabetes mellitus, 77, 355, 356 Insulin-like, 8, 39, 75, 105, 283, 356 Intensive Care, 188, 189, 216, 239, 356 Intensive Care Units, 216, 356 Interleukin-1, 33, 43, 356 Interleukin-15, 43, 356 Interleukin-18, 43, 356 Interleukin-2, 356 Intermittent, 17, 356, 360, 373, 376, 381 Interstitial, 32, 62, 203, 204, 228, 236, 343, 356, 366, 384 Intestinal, 247, 325, 327, 340, 347, 356, 361 Intestines, 207, 309, 343, 345, 356, 387 Intoxication, 334, 356, 400 Intravascular, 349, 356 Intravenous, 21, 90, 153, 205, 306, 355, 356, 382 Intrinsic, 25, 31, 176, 192, 199, 201, 214, 221, 311, 319, 356 Intubation, 325, 356 Invasive, 16, 18, 51, 57, 154, 176, 186, 353, 356, 361 Investigative Techniques, 33, 356 Involuntary, 319, 344, 357, 366, 383, 388, 389 Ion Channels, 37, 357, 368 Ionization, 11, 357 Ions, 319, 322, 323, 336, 337, 339, 346, 348, 351, 355, 357, 364, 377, 380, 386, 389 Ischemia, 11, 16, 27, 31, 37, 43, 183, 200, 211, 215, 318, 357, 366, 384 Isoenzyme, 225, 332, 350, 357 Isoleucine, 38, 357 Isomerases, 226, 357 Isopropyl, 205, 357 Isozymes, 12, 357 J Jaundice, 235, 350, 352, 357 Joint, 244, 357, 392, 393 K Kallidin, 321, 357 Kb, 274, 357 Ketone Bodies, 335, 357 Ketosis, 335, 357 Kidney Cortex, 357, 363 Kidney Disease, 4, 173, 235, 236, 237, 238, 247, 248, 258, 274, 312, 358, 384
Index 413
Kidney Failure, 250, 258, 286, 287, 340, 347, 358 Kidney Failure, Acute, 358 Kidney Failure, Chronic, 258, 358 Kidney stone, 236, 238, 258, 358, 367, 397 Kidney Transplantation, 358 Kinetics, 148, 256, 358 L Labile, 329, 358 Laceration, 358, 394 Large Intestine, 335, 336, 356, 358, 383, 389 Larynx, 347, 358, 395, 398 Latent, 358, 378 Laxative, 126, 311, 358, 390 LDL, 116, 209, 287, 338, 358, 360 Left ventricular assist device, 19, 36, 65, 94, 161, 358 Leprosy, 344, 358 Leptin, 17, 359 Lesion, 286, 331, 344, 359, 360 Lethal, 37, 318, 359 Leucine, 38, 57, 359 Leucocyte, 312, 359 Leukemia, 200, 337, 359 Leukocytes, 319, 321, 326, 327, 341, 348, 354, 359, 364, 368, 397 Leukotrienes, 316, 359 Library Services, 298, 359 Lidocaine, 319, 359 Life cycle, 310, 345, 359 Life Expectancy, 36, 359 Ligament, 359, 379 Ligands, 212, 216, 359, 383 Ligase, 13, 359 Ligation, 25, 45, 47, 61, 211, 359 Linkage, 177, 359 Lip, 89, 98, 114, 359 Lipid, 19, 25, 223, 288, 317, 323, 325, 355, 359, 360, 365, 371, 396 Lipid A, 25, 359 Lipid Peroxidation, 359, 371 Lipophilic, 219, 359 Lipopolysaccharides, 177, 359 Lipoprotein, 338, 348, 358, 360 Lisinopril, 130, 144, 360 Lithium, 176, 236, 360 Liver Cirrhosis, 350, 360 Liver scan, 360, 386 Liver Transplantation, 235, 360 Localization, 353, 360 Localized, 213, 228, 313, 330, 334, 336, 354, 360, 375, 386, 394, 398
Lockjaw, 288, 360 Locomotion, 360, 375 Long-Term Care, 22, 360 Loop, 114, 144, 201, 265, 360 Low-density lipoprotein, 338, 358, 360 Lumen, 316, 340, 360 Lupus, 360, 393 Lymph, 95, 258, 326, 327, 340, 360, 361, 362, 386, 391 Lymph node, 95, 258, 326, 360, 361, 362, 386 Lymphatic, 340, 355, 360, 361, 363, 389, 390 Lymphatic system, 360, 361, 389, 390 Lymphocyte, 315, 356, 361, 362 Lymphoid, 315, 359, 361 Lymphoma, 112, 139, 361 M Macrophage, 356, 361 Magnetic Resonance Imaging, 158, 361, 386 Magnetic Resonance Spectroscopy, 18, 361 Malabsorption, 247, 361 Malignant, 74, 316, 361, 366, 370, 393 Malnutrition, 117, 133, 250, 311, 318, 322, 324, 361 Mammary, 331, 361 Mammogram, 322, 361, 363 Mania, 361 Manic, 216, 225, 360, 361, 380 Manic-depressive psychosis, 361, 380 Manifest, 46, 361 Matrix metalloproteinase, 33, 35, 49, 62, 361 Meat, 285, 361, 386 Meatus, 361, 398 Mechanoreceptors, 37, 348, 361 Medial, 65, 317, 362 Mediastinum, 71, 362 Mediate, 16, 31, 62, 202, 216, 337, 362 Mediator, 216, 219, 327, 356, 362, 388 Medical Records, 6, 40, 53, 362 Medicament, 205, 229, 362 MEDLINE, 275, 362 Medullary, 236, 362 Megaloblastic, 344, 362 Melanin, 362, 374, 397 Membrane Glycoproteins, 362 Membrane Proteins, 325, 362 Memory, 111, 315, 334, 362 Meninges, 326, 338, 362
414 Heart Failure
Meningitis, 286, 362 Menopause, 166, 362, 377 Menstrual Cycle, 362, 378 Mental Disorders, 173, 362, 380 Mental Health, iv, 6, 173, 274, 276, 362, 381 Mental Retardation, 216, 225, 362 Mesenchymal, 11, 341, 363 Meta-Analysis, 131, 363 Metabolic disorder, 284, 285, 334, 363 Metabolic therapy, 119, 363 Metabolite, 18, 33, 363, 378, 382 Metallothionein, 45, 363 Metastasis, 361, 363 Metoprolol, 74, 75, 79, 81, 91, 96, 97, 102, 125, 129, 255, 363 MI, 40, 44, 45, 46, 138, 167, 194, 201, 204, 257, 286, 287, 307, 363 Microbe, 363, 395 Microbiology, 310, 318, 363 Microcalcifications, 322, 363 Microcirculation, 238, 360, 363 Microdialysis, 32, 49, 363 Microorganism, 328, 363, 400 Microscopy, 13, 46, 49, 64, 319, 363 Migration, 11, 219, 363 Milligram, 5, 363 Milliliter, 284, 364 Mitochondria, 35, 85, 147, 364, 366, 370, 391 Mitochondrial Swelling, 364, 366 Mitosis, 316, 364 Mitral Valve, 92, 193, 364 Mobility, 14, 209, 364 Mobilization, 209, 364 Modeling, 24, 58, 60, 172, 364 Modification, 91, 364, 381 Modulator, 84, 364 Molecular Structure, 364, 396 Monitor, 17, 160, 180, 187, 189, 207, 208, 228, 286, 287, 327, 332, 364, 369 Monoclonal, 353, 364, 382 Monoclonal antibodies, 353, 364 Monocytes, 356, 359, 364, 394 Monogenic, 23, 364 Mononuclear, 364, 397 Mood Disorders, 23, 54, 364 Morphological, 55, 339, 365 Morphology, 13, 45, 52, 55, 176, 365 Motility, 346, 354, 365, 388 Motion Sickness, 365, 366 Movement Disorders, 365
Mucosa, 327, 340, 360, 365 Multiple sclerosis, 225, 365 Multivariate Analysis, 4, 168, 365 Muscle Contraction, 61, 207, 365, 386 Muscle Fibers, 317, 365, 366, 396 Muscle Proteins, 330, 365 Muscle Relaxation, 207, 365 Mydriatic, 336, 365 Myelin, 365 Myelosuppression, 216, 365 Myocardial Contraction, 30, 365 Myocardial Ischemia, 35, 37, 70, 176, 190, 197, 211, 215, 314, 331, 365 Myocardial Reperfusion, 365, 366, 384 Myocardial Reperfusion Injury, 366, 384 Myocarditis, 87, 176, 224, 336, 366 Myoglobin, 183, 366, 376 Myopathy, 19, 43, 148, 218, 366 Myosin, 41, 56, 58, 148, 192, 206, 309, 322, 365, 366, 396 N Narcosis, 351, 366 Natriuresis, 219, 314, 366 Nausea, 258, 303, 337, 357, 366, 397 NCI, 1, 172, 273, 327, 366 Necrosis, 43, 46, 116, 200, 316, 354, 363, 365, 366, 384, 386 Neonatal, 14, 44, 236, 366 Neoplasm, 366, 397 Neoplastic, 361, 366 Nephritis, 236, 366 Nephrogenic, 223, 367 Nephrolithiasis, 236, 367 Nephrologist, 4, 367 Nephrology, 3, 4, 114, 238, 250, 367 Nephron, 203, 347, 367 Nephropathy, 205, 218, 236, 237, 238, 358, 367 Nephrosis, 350, 367 Nephrotic, 233, 367 Nephrotic Syndrome, 233, 367 Nervous System, 17, 188, 199, 212, 219, 255, 309, 311, 313, 318, 319, 322, 326, 327, 328, 338, 345, 347, 348, 359, 362, 365, 367, 368, 372, 388, 392 Neural, 107, 188, 311, 362, 367, 389 Neuregulin-1, 42, 367 Neurodegenerative Diseases, 212, 319, 367 Neuroendocrine, 15, 63, 367 Neurogenic, 367, 397 Neurologic, 232, 235, 367 Neuromuscular, 119, 309, 367
Index 415
Neuromuscular Junction, 309, 367 Neuronal, 221, 366, 367 Neurons, 36, 61, 221, 328, 334, 342, 345, 367, 368, 392, 393 Neuropathy, 199, 205, 238, 318, 367 Neuropeptides, 212, 367 Neurophysiology, 334, 368 Neurotransmitters, 226, 368, 390 Neutralization, 178, 368 Neutrons, 312, 368, 381 Neutropenia, 216, 368 Neutrophils, 326, 348, 359, 368 Niacin, 368, 396 Nifedipine, 176, 368 Nitrates, 194, 267, 368 Nitric acid, 368 Nitric Oxide, 24, 43, 45, 47, 52, 80, 118, 195, 238, 368 Nitrogen, 48, 205, 258, 312, 313, 343, 358, 368, 396 Nocturia, 260, 303, 368 Nodose, 37, 368 Nonverbal Communication, 368, 381 Norepinephrine, 168, 219, 310, 311, 337, 368 N-terminal, 72, 81, 98, 99, 109, 221, 369 Nuclear, 8, 9, 50, 94, 131, 133, 134, 135, 237, 305, 319, 328, 339, 342, 345, 366, 369 Nuclei, 32, 312, 339, 361, 364, 368, 369, 380 Nucleic acid, 196, 346, 351, 353, 354, 368, 369, 381 Nucleic Acid Hybridization, 351, 369 Nucleus, 316, 319, 327, 332, 333, 334, 339, 341, 342, 364, 368, 369, 380, 389, 391 O Observational study, 40, 369 Ocular, 237, 369 Odds Ratio, 369, 383 Odour, 316, 369 Ointments, 337, 369 Olfaction, 223, 327, 369 Oliguria, 303, 358, 369 Oncogene, 8, 369 On-line, 53, 301, 369 Opacity, 334, 369 Operon, 369, 384 Ophthalmologic, 338, 370 Opsin, 370, 385 Optic Disk, 331, 335, 370 Oral Health, 231, 370 Organ Transplantation, 232, 235, 370 Organelles, 333, 364, 370
Osmosis, 370 Osmotic, 74, 311, 364, 370, 388 Osteogenic sarcoma, 370 Osteopathic Medicine, 137, 370 Osteoporosis, 141, 209, 216, 221, 225, 312, 341, 370 Osteosarcoma, 221, 370 Outpatient, 6, 21, 40, 157, 165, 168, 237, 370 Ovaries, 370, 384, 393 Overactive bladder, 204, 370 Overdose, 232, 370 Overweight, 119, 284, 286, 370 Ovum, 332, 359, 370, 378 Oxidation, 13, 18, 25, 49, 50, 119, 194, 309, 316, 327, 332, 335, 347, 359, 370, 371 Oxidative Phosphorylation, 49, 371 Oxidative Stress, 24, 35, 43, 45, 46, 47, 48, 66, 92, 104, 178, 211, 371 Oxygen Consumption, 18, 19, 47, 75, 129, 147, 167, 194, 340, 342, 371, 384 Oxygenator, 324, 343, 371 Oxypurinol, 156, 371 P Pacemaker, 182, 222, 256, 371 Pachymeningitis, 362, 371 Palliative, 128, 135, 371, 394 Pancreas, 309, 320, 335, 349, 355, 371, 396 Pancreatic, 324, 327, 345, 371 Paralysis, 288, 311, 371 Parasitic, 319, 371, 385 Parotid, 371, 386 Paroxysmal, 314, 371, 373, 400 Partial remission, 371, 384 Particle, 371, 390, 396 Partnership Practice, 371, 378 Patch, 30, 37, 331, 371 Pathogenesis, 8, 25, 42, 45, 48, 58, 61, 65, 233, 236, 371 Pathologic, 9, 15, 34, 41, 43, 66, 182, 185, 195, 309, 316, 320, 331, 352, 371, 372, 380 Pathologic Processes, 316, 372 Pathologies, 46, 199, 372 Patient Care Team, 285, 372 Patient Compliance, 171, 372 Patient Education, 128, 284, 296, 298, 307, 372 Patient Satisfaction, 157, 168, 372 Pelvic, 260, 372, 379 Penicillin, 286, 315, 323, 372 Penicillinase, 323, 372 Penis, 330, 372, 384
416 Heart Failure
Peptide T, 44, 73, 372 Percutaneous, 185, 372 Perfusion, 43, 51, 108, 136, 176, 207, 227, 345, 353, 372, 381 Pericardium, 372, 393, 399 Perioperative, 238, 372 Peripheral Nervous System, 224, 340, 367, 372, 392 Peripheral Vascular Disease, 219, 237, 238, 372 Peritoneal, 4, 236, 317, 373 Peritoneal Cavity, 317, 373 Peritoneal Dialysis, 4, 236, 373 Peritoneum, 373 Peritonitis, 235, 373 Peroneal Nerve, 33, 373, 386 Pertussis, 288, 373, 400 PH, 64, 77, 136, 260, 373 Pharmaceutical Preparations, 197, 326, 342, 345, 373 Pharmaceutical Solutions, 337, 373 Pharmacodynamic, 44, 66, 373 Pharmacokinetic, 44, 163, 373 Pharmacologic, 4, 12, 34, 234, 314, 318, 348, 374, 395, 397 Pharmacotherapy, 118, 138, 374 Pharynx, 374, 398 Phenotype, 14, 15, 24, 32, 33, 59, 63, 68, 203, 374 Phenyl, 179, 190, 197, 215, 224, 225, 336, 374 Phenylalanine, 374, 397 Phlebotomy, 284, 285, 374 Phorbol, 374, 379 Phorbol Esters, 374, 379 Phosphates, 38, 49, 374 Phosphodiesterase, 38, 52, 116, 194, 205, 218, 225, 226, 313, 340, 374 Phosphodiesterase Inhibitors, 194, 374 Phospholipases, 374, 388 Phospholipids, 343, 355, 360, 374, 379 Phosphoprotein Phosphatase, 37, 374 Phosphorus, 323, 374 Phosphorylate, 195, 374 Phosphorylated, 11, 50, 64, 195, 223, 317, 328, 374 Phosphorylation, 10, 13, 14, 38, 64, 177, 216, 367, 374, 380 Photosensitivity, 375, 376 Phototransduction, 223, 316, 375, 387 Physical Examination, 6, 102, 158, 191, 248, 375
Pigment, 320, 366, 370, 375 Pilot study, 29, 135, 159, 375 Pituitary Gland, 219, 375 Placenta, 375, 378 Plants, 223, 312, 319, 320, 322, 323, 324, 328, 336, 346, 347, 365, 369, 375, 395 Plaque, 224, 314, 375 Plasma, 26, 96, 103, 105, 116, 170, 194, 200, 205, 226, 311, 315, 321, 326, 340, 344, 345, 347, 350, 352, 358, 363, 375, 380, 383, 384, 387, 388 Plasma cells, 315, 375 Plasma protein, 311, 340, 375, 380, 388 Plasma Volume, 170, 321, 375 Platelet Activation, 375, 389 Platelet Aggregation, 81, 221, 314, 368, 375, 394 Platelets, 229, 326, 365, 368, 375, 376, 394, 395 Platinum, 360, 376 Plethysmography, 176, 376 Poisoning, 334, 356, 366, 376 Polycystic, 238, 376 Polymerase, 376, 384 Polymorphic, 196, 376 Polymorphism, 48, 376 Polypeptide, 192, 216, 313, 328, 341, 344, 351, 366, 376, 394, 396, 401 Popliteal, 224, 343, 376 Popliteal Vein, 343, 376 Porphyria, 285, 374, 376 Porphyria Cutanea Tarda, 285, 374, 376 Porphyria, Hepatic, 376 Porphyrins, 376 Portal Vein, 352, 376 Posterior, 313, 317, 337, 371, 376, 377 Postmenopausal, 166, 312, 341, 370, 377 Postnatal, 39, 51, 377, 391 Postoperative, 124, 135, 235, 377 Postprandial, 56, 377 Postsynaptic, 377, 388, 392 Post-translational, 48, 377 Postural, 232, 237, 377 Potassium, 23, 32, 37, 39, 121, 233, 237, 258, 265, 281, 312, 337, 377 Potassium Channels, 23, 377 Potentiate, 43, 377 Potentiating, 206, 377 Potentiation, 377, 388 Power Sources, 179, 377 Practicability, 377, 396 Practice Guidelines, 164, 168, 276, 289, 377
Index 417
Prazosin, 145, 194, 240, 267, 377 Precipitating Factors, 325, 377 Preclinical, 8, 377 Precursor, 40, 219, 314, 316, 337, 338, 340, 368, 374, 377, 378, 380, 396, 397 Predisposition, 196, 378 Pregnancy in Diabetics, 335, 378 Preload, 65, 176, 378 Premarin, 209, 378 Pressoreceptors, 319, 378 Prevalence, 4, 5, 6, 8, 21, 29, 36, 41, 44, 54, 101, 163, 191, 217, 220, 238, 259, 291, 369, 378 Primary Biliary Cirrhosis, 235, 378 Primary endpoint, 60, 378 Private Practice, 253, 378 Probe, 56, 59, 104, 190, 348, 363, 378 Procaine, 311, 359, 378 Prodrug, 378, 382 Progesterone, 209, 378, 391 Projection, 368, 378 Proline, 328, 352, 378 Promoter, 13, 42, 378 Prone, 184, 232, 378 Prone Position, 232, 378 Prophylaxis, 199, 200, 378 Propulsive, 187, 197, 378 Prostaglandin, 195, 314, 379, 394 Prostaglandins A, 354, 379 Prostate, 260, 319, 320, 379, 384, 396 Prostate gland, 260, 379 Prostatic Hyperplasia, 379 Protease, 220, 329, 379 Protective Agents, 323, 379 Protein C, 31, 195, 202, 209, 221, 225, 309, 311, 313, 318, 344, 360, 365, 379, 396, 397 Protein Kinase C, 12, 379 Protein S, 51, 61, 216, 226, 245, 320, 346, 379, 385, 394 Protein-Tyrosine Kinase, 346, 380 Proteinuria, 218, 236, 237, 347, 367, 380 Proteolytic, 62, 221, 312, 329, 344, 380 Prothrombin, 380, 394 Protocol, 54, 136, 149, 170, 171, 380 Protons, 312, 351, 361, 380, 381 Protozoa, 363, 380 Proximal, 50, 222, 337, 357, 380, 387 Psoriasis, 201, 216, 380 Psychiatric, 54, 232, 235, 362, 380 Psychiatry, 22, 54, 380, 399 Psychic, 380, 387 Psychogenic, 380, 397
Psychomotor, 334, 380 Psychosis, 286, 380 Psychotherapy, 27, 380 Public Health, 11, 39, 51, 167, 238, 246, 251, 276, 381 Public Policy, 275, 381 Pulmonary Alveoli, 353, 381 Pulmonary Artery, 52, 154, 208, 213, 289, 321, 381, 399 Pulmonary congestion, 207, 381 Pulmonary Edema, 51, 108, 158, 162, 188, 191, 232, 242, 248, 256, 358, 381 Pulmonary Embolism, 176, 381 Pulmonary hypertension, 52, 216, 218, 289, 381 Pulmonary Valve, 349, 381 Pulmonary Ventilation, 352, 381, 385 Pulsatile Flow, 10, 381 Pulse, 16, 176, 180, 182, 187, 198, 305, 364, 381 Pupil, 336, 365, 381 Purgative, 358, 381 Purines, 381, 388, 400 R Race, 53, 79, 233, 234, 286, 287, 363, 381 Radiation, 214, 309, 310, 314, 339, 340, 344, 381, 382, 386, 400, 401 Radiation therapy, 309, 310, 381 Radioactive, 321, 348, 351, 354, 357, 360, 364, 369, 382, 386 Radioisotope, 341, 382, 395 Radioisotope Renography, 382 Radiological, 372, 382 Radionuclide Angiography, 59, 382 Ramipril, 145, 223, 382 Random Allocation, 382 Randomization, 60, 168, 169, 382 Randomized clinical trial, 167, 382 Reabsorption, 233, 382 Reactivation, 13, 382 Reactive Oxygen Species, 17, 45, 47, 48, 382 Reality Testing, 380, 382 Receptors, Opioid, 195, 338, 383 Receptors, Serotonin, 383, 388 Recombinant, 42, 51, 64, 216, 383, 398 Recombinant Proteins, 64, 383 Reconstitution, 43, 383 Rectum, 316, 321, 335, 336, 344, 345, 358, 379, 383 Red blood cells, 258, 259, 341, 350, 365, 376, 383
418 Heart Failure
Reductase, 121, 205, 383 Reentry, 14, 383 Refer, 1, 238, 329, 340, 345, 360, 368, 380, 383, 387 Reflex, 32, 37, 61, 84, 115, 188, 383 Reflux, 185, 383 Refraction, 383, 390 Refractory, 129, 383 Regeneration, 11, 19, 43, 156, 383 Regimen, 52, 148, 171, 188, 189, 338, 372, 374, 383 Regurgitation, 68, 187, 192, 197, 259, 349, 383 Relative risk, 5, 383 Relaxin, 99, 384 Reliability, 28, 384 Remission, 22, 361, 384 Renal Artery, 352, 384 Renal failure, 4, 178, 181, 218, 227, 334, 350, 384 Renal Osteodystrophy, 236, 384 Renal pelvis, 358, 384 Renin, 43, 59, 62, 79, 110, 114, 119, 149, 170, 176, 219, 233, 238, 242, 314, 323, 384 Renin-Angiotensin System, 43, 238, 314, 323, 384 Reperfusion, 16, 27, 31, 44, 366, 384 Reperfusion Injury, 27, 31, 384 Repressor, 9, 370, 384 Reproductive system, 379, 384 Residential Facilities, 249, 384 Respiration, 68, 92, 187, 188, 197, 316, 323, 364, 384 Respiratory failure, 343, 385 Respiratory System, 184, 194, 385 Restoration, 20, 24, 60, 159, 365, 382, 383, 384, 385, 400 Retina, 330, 331, 335, 375, 385, 386, 398 Retinal, 224, 316, 335, 370, 375, 385 Retinol, 385 Retinopathy, 238, 335, 385 Retrograde, 51, 385 Reversion, 50, 385 Rheumatic Heart Disease, 232, 235, 385 Rheumatism, 385 Rheumatoid, 195, 216, 385 Rheumatoid arthritis, 195, 216, 385 Ribose, 310, 385 Ribosome, 385, 396 Rickettsiae, 385 Rigidity, 375, 385
Risk factor, 4, 5, 6, 16, 22, 91, 105, 176, 233, 238, 250, 284, 286, 287, 288, 325, 383, 385 Rod, 318, 328, 348, 386 Rosiglitazone, 157, 158, 386 Rubella, 288 Ryanodine, 38, 386 S Saline, 129, 201, 386 Salivary, 333, 335, 386, 391 Salivary glands, 333, 335, 386 Saphenous, 331, 386 Saphenous Vein, 331, 386 Sarcoidosis, 258, 386 Sarcomere, 206, 386 Sarcoplasmic Reticulum, 7, 8, 20, 38, 55, 58, 192, 215, 386 Saturated fat, 288, 386 Scans, 305, 386 Schizophrenia, 216, 225, 386, 400 Sciatic Nerve, 373, 386 Scleroderma, 218, 288, 289, 386 Sclerosis, 218, 317, 365, 386 Screening, 5, 26, 34, 105, 158, 210, 211, 259, 284, 328, 386, 397 Second Messenger Systems, 368, 386 Secretion, 212, 310, 338, 341, 351, 356, 387 Secretory, 15, 326, 387, 392 Secretory Vesicles, 326, 387 Secular trends, 40, 387 Sedentary, 167, 387 Sediment, 387, 397 Segmental, 233, 347, 387 Segmentation, 387 Seizures, 232, 334, 371, 387 Selenium, 116, 387 Self Care, 237, 309, 387 Sella, 337, 375, 387 Semen, 379, 387 Semisynthetic, 323, 324, 387 Senile, 211, 212, 249, 370, 387 Sensor, 176, 184, 189, 197, 199, 387 Sepsis, 176, 216, 387 Septal, 110, 130, 193, 387 Septic, 215, 216, 387 Septum, 192, 221, 317, 387 Septum Pellucidum, 387 Sequence Homology, 372, 388 Sequencing, 59, 388 Serine, 39, 216, 220, 374, 379, 388 Serologic, 353, 388 Serology, 53, 388
Index 419
Serotonin, 85, 205, 226, 334, 343, 374, 383, 388, 396 Serous, 340, 388 Serum, 4, 6, 105, 117, 160, 163, 169, 183, 305, 311, 314, 329, 332, 358, 360, 373, 383, 388, 397 Serum Albumin, 4, 388 Sexual Abstinence, 286, 388 Sexually Transmitted Diseases, 232, 235, 388 Shivering, 190, 388 Shock, 14, 110, 204, 215, 216, 314, 388, 396 Side effect, 163, 193, 201, 231, 233, 263, 311, 313, 320, 365, 388, 395 Siderosis, 285, 388 Signal Transduction, 10, 12, 14, 16, 44, 52, 55, 64, 150, 201, 216, 221, 226, 322, 325, 355, 388 Signs and Symptoms, 3, 6, 203, 235, 248, 281, 384, 389 Skeleton, 309, 343, 357, 379, 389 Skull, 389, 393 Sleep apnea, 17, 99, 134, 183, 184, 233, 389 Small intestine, 320, 338, 351, 356, 389 Smoke Inhalation Injury, 343, 389 Smooth muscle, 24, 37, 43, 52, 219, 221, 229, 314, 318, 322, 323, 351, 384, 389, 392 Sneezing, 373, 389 Social Environment, 381, 389 Social Support, 22, 28, 54, 149, 150, 389 Social Work, 157, 389 Sodium, 169, 176, 203, 222, 223, 233, 237, 245, 305, 312, 337, 366, 375, 382, 389 Sodium Channels, 375, 389 Soft tissue, 321, 389 Solid tumor, 314, 337, 389 Solitary Nucleus, 318, 389 Solvent, 342, 370, 373, 390 Soma, 390 Somatic, 7, 55, 326, 364, 372, 390, 398 Somatic cells, 326, 364, 390 Sorbitol, 350, 390 Sotalol, 176, 390 Sound wave, 330, 390, 397 Spasmodic, 373, 390 Specialist, 4, 243, 248, 282, 292, 336, 390 Specificity, 201, 311, 390 Spectrum, 41, 57, 323, 390 Spinal cord, 286, 326, 327, 338, 362, 367, 371, 372, 383, 386, 390, 392 Spinal Nerves, 372, 390 Spirochete, 390, 393
Spleen, 258, 313, 333, 360, 361, 386, 390 Splint, 180, 184, 390 Sporadic, 367, 376, 390 Staging, 386, 391 Standard therapy, 151, 164, 391 Statistically significant, 259, 391 Steatosis, 343, 391 Steel, 212, 328, 391 Stem Cells, 11, 254, 391 Steroid, 320, 324, 332, 391 Stimulant, 313, 322, 337, 351, 357, 391 Stimulus, 13, 33, 43, 213, 331, 337, 338, 339, 342, 355, 357, 383, 391, 394 Stomach, 207, 309, 335, 336, 341, 345, 347, 351, 356, 357, 366, 373, 374, 383, 389, 390, 391 Strand, 9, 376, 391 Stroke Volume, 66, 191, 197, 213, 214, 324, 391 Stroma, 388, 391 Subacute, 354, 391 Subclinical, 354, 387, 391 Subcutaneous, 310, 338, 391 Submaxillary, 341, 391 Submitochondrial Particles, 35, 391 Subspecies, 390, 392 Substance P, 363, 383, 387, 392 Substrate, 14, 18, 19, 23, 49, 50, 200, 206, 341, 357, 392 Suction, 344, 392 Sudden cardiac death, 59, 392 Sudden death, 22, 59, 79, 183, 196, 199, 201, 220, 229, 392 Superoxide, 45, 47, 48, 392 Superoxide Dismutase, 48, 392 Supplementation, 18, 123, 127, 132, 133, 285, 392 Suppression, 45, 62, 392 Supraventricular, 218, 220, 392 Survival Rate, 21, 44, 46, 63, 153, 165, 255, 392 Sympathetic Nervous System, 176, 214, 219, 314, 318, 392 Sympathomimetic, 204, 313, 337, 341, 369, 392 Symphysis, 379, 392 Symptomatic, 74, 92, 103, 162, 203, 335, 344, 378, 392 Synapses, 368, 392 Synaptic, 388, 392 Syncope, 232, 393 Synergistic, 12, 43, 60, 393
420 Heart Failure
Syphilis, 286, 393 Systemic disease, 235, 236, 393 Systemic lupus erythematosus, 236, 393 Systole, 35, 185, 192, 332, 349, 393 Systolic heart failure, 26, 48, 68, 101, 115, 206, 393 Systolic pressure, 13, 286, 393 T Tachycardia, 23, 59, 64, 132, 220, 337, 393 Tamponade, 251, 393 Telecommunications, 153, 393 Telomere, 43, 393 Temporal, 40, 48, 60, 161, 361, 393 Teratogenic, 336, 393 Teratoma, 71, 393 Testicles, 393 Testicular, 216, 393 Testis, 393 Testosterone, 383, 393 Tetani, 394 Tetanic, 394 Tetanus, 288, 394 Tetracycline, 27, 59, 394 Thalassemia, 131, 394 Thalidomide, 116, 394 Therapeutics, 65, 114, 119, 134, 194, 204, 232, 269, 356, 394 Thermal, 108, 130, 138, 336, 368, 394 Thiamine, 120, 324, 394 Thigh, 343, 394 Thorax, 187, 309, 394, 398 Threonine, 11, 39, 216, 372, 374, 379, 388, 394 Threshold, 5, 14, 182, 197, 207, 213, 286, 342, 352, 394 Thrombin, 220, 226, 228, 229, 344, 375, 379, 380, 394 Thrombocytes, 376, 394 Thrombocytopenia, 313, 394 Thrombomodulin, 379, 394 Thrombosis, 22, 83, 114, 220, 228, 238, 380, 391, 394 Thromboxanes, 316, 394 Thrombus, 10, 331, 354, 365, 366, 376, 395 Thyroid, 119, 163, 191, 232, 235, 250, 352, 395, 397 Thyroid Gland, 232, 352, 395 Thyroid Hormones, 395, 397 Thyrotoxicosis, 176, 395 Thyroxine, 311, 374, 395 Tidal Volume, 186, 197, 352, 395 Tolerance, 31, 162, 310, 347, 395
Tomography, 95, 128, 129, 361, 395 Tonic, 324, 360, 395 Tonicity, 350, 395 Tooth Preparation, 310, 395 Topical, 267, 342, 351, 395 Torsion, 354, 395 Toxic, iv, 194, 224, 235, 258, 319, 324, 333, 336, 340, 348, 353, 367, 368, 370, 387, 389, 395 Toxicity, 4, 16, 47, 126, 235, 258, 337, 395 Toxicology, 8, 37, 276, 395 Toxins, 176, 258, 315, 354, 364, 395 Tracer, 56, 395 Trachea, 322, 358, 362, 374, 395 Traction, 328, 395 Transcription Factors, 32, 33, 39, 46, 50, 63, 396 Transduction, 16, 36, 50, 52, 216, 226, 388, 396 Transfection, 320, 396 Transgenes, 26, 59, 64, 396 Translation, 9, 396 Translational, 9, 396 Translocation, 8, 396 Transmitter, 309, 337, 357, 362, 368, 392, 396 Transplantation, 10, 48, 64, 65, 95, 133, 199, 201, 210, 235, 236, 238, 244, 254, 327, 396 Trauma, 258, 319, 334, 348, 366, 396 Treatment Outcome, 28, 150, 396 Tricyclic, 146, 176, 228, 396 Triglyceride, 352, 396 Tropomyosin, 206, 365, 396 Troponin, 10, 41, 48, 64, 183, 206, 365, 396 Troponin C, 206, 396 Truncal, 209, 396 Tryptophan, 11, 329, 388, 396 Tuberculosis, 330, 360, 396 Tumor marker, 320, 396 Tumor Necrosis Factor, 46, 63, 284, 394, 397 Tumour, 116, 397 Type 2 diabetes, 6, 93, 397 Tyrosine, 12, 42, 49, 337, 380, 397 U Ubiquitin, 62, 397 Ultrafiltration, 99, 228, 245, 350, 397 Ultrasound test, 158, 397 Unconscious, 314, 353, 397 Urea, 237, 258, 358, 397 Uremia, 232, 358, 384, 397
Index 421
Ureters, 358, 384, 397 Urethra, 260, 319, 372, 379, 397, 398 Uric, 312, 381, 397 Urinalysis, 158, 237, 305, 397 Urinary, 92, 216, 225, 236, 237, 256, 318, 332, 346, 369, 377, 397, 398, 400 Urinary Retention, 216, 225, 377, 397 Urinary tract, 236, 238, 318, 397 Urinary tract infection, 236, 238, 318, 397 Urinate, 260, 303, 397 Urogenital, 346, 398 Uroporphyrinogen Decarboxylase, 376, 398 Urticaria, 314, 398 Uterus, 326, 331, 370, 378, 384, 393, 398 Uveitis, 317, 398 V Vaccine, 310, 380, 398 Vagal, 37, 199, 398 Vagina, 334, 384, 393, 398 Vaginal, 286, 398 Vagus Nerve, 198, 389, 396, 398 Valves, 184, 185, 187, 197, 385, 398, 399 Varicella, 288, 398 Vasa Nervorum, 224, 398 Vascular endothelial growth factor, 65, 131, 398 Vascular Resistance, 176, 202, 313, 319, 398 Vasoactive, 219, 398 Vasoconstriction, 130, 219, 337, 341, 398 Vasodilatation, 225, 357, 398 Vasodilation, 52, 130, 170, 218, 314, 398 Vasodilator, 52, 250, 313, 322, 337, 351, 366, 368, 398 Vasomotor, 170, 171, 341, 398 VE, 153, 171, 398 Vector, 51, 396, 398 Vein, 132, 184, 185, 314, 317, 343, 353, 356, 369, 371, 374, 376, 386, 399 Venereal, 393, 399 Venous, 56, 184, 185, 203, 208, 214, 317, 333, 352, 380, 399 Venous blood, 185, 208, 399 Venous Pressure, 184, 185, 203, 399 Ventilation, 324, 399 Ventricular Dysfunction, 25, 43, 70, 73, 78, 87, 137, 165, 186, 218, 338, 399 Ventricular fibrillation, 14, 399
Ventricular Function, 15, 17, 50, 52, 128, 129, 167, 220, 247, 345, 399 Ventricular Pressure, 50, 66, 192, 399 Ventricular Remodeling, 11, 15, 33, 92, 136, 161, 163, 399 Venules, 321, 323, 340, 363, 399 Verapamil, 129, 176, 268, 399 Vertebrae, 390, 399 Veterinary Medicine, 223, 275, 399 Viral, 7, 51, 62, 176, 205, 210, 215, 216, 225, 235, 346, 396, 399 Viral Hepatitis, 235, 399 Viral vector, 7, 51, 62, 215, 399 Virulence, 318, 395, 400 Virus, 51, 286, 318, 320, 340, 346, 347, 375, 396, 399, 400 Viscera, 390, 400 Visceral, 318, 373, 398, 400 Visceral Afferents, 318, 398, 400 Vitamin A, 355, 385, 400 Vitreous Hemorrhage, 335, 400 Vitro, 13, 18, 19, 36, 38, 42, 44, 45, 53, 400 Vivo, 7, 11, 13, 14, 18, 19, 24, 33, 34, 36, 37, 38, 42, 43, 48, 50, 51, 53, 56, 62, 66, 195, 198, 215, 221, 326, 354, 363, 394, 400 Voltage-gated, 36, 400 W Wakefulness, 334, 400 War, 351, 400 Weight Gain, 6, 400 White blood cell, 315, 359, 361, 365, 368, 375, 400 Whooping Cough, 288, 373, 400 Windpipe, 374, 395, 400 Withdrawal, 334, 400 Wound Healing, 209, 361, 400 X Xanthine, 47, 65, 66, 217, 312, 371, 400 Xanthine Oxidase, 47, 65, 66, 217, 312, 371, 400 Xenograft, 315, 400 X-ray, 158, 191, 214, 304, 306, 330, 344, 361, 369, 381, 386, 400, 401 X-ray tube, 214, 401 Y Yeasts, 345, 374, 401 Z Zymogen, 379, 401
422 Heart Failure
Index 423
424 Heart Failure
